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Sample records for cell cycle stage

  1. Chromatin remodeling by cell cycle stage-specific extracts from Physarum polycephalum.

    Science.gov (United States)

    Thiriet, C; Hayes, J J

    1999-03-01

    Remodeling of chromatin is an essential process allowing the establishment of specific genetic programs. The slime mold Physarum polycephalum presents the attractive advantage of natural synchrony of the cell cycle in several million nuclei. Whole-cell extracts prepared at precise stages during the cell cycle were tested for the ability to induce remodeling in erythrocyte nuclei as monitored by microscopy, protamine competition assays, micrococcal nuclease digestions, and release of histone H5. Extracts derived from two specific cell cycle stages caused opposite types of changes in erythrocyte nuclei. An increase in chromatin compaction was imparted by extracts prepared during S-phase while extracts harvested at the end of G2-phase caused increases in nuclear volume, DNA accessibility, and release of linker histone. We also found that late G2 extracts had the ability to alter the DNase I digestion profile of mononucleosomes reconstituted in vitro in a classical nucleosomes remodeling assay. The relevance of these finding to the Physarum cell cycle is discussed. PMID:10219572

  2. Sorting of cells of the same size, shape, and cell cycle stage for a single cell level assay without staining

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    Yomo Tetsuya

    2006-06-01

    Full Text Available Abstract Background Single-cell level studies are being used increasingly to measure cell properties not directly observable in a cell population. High-performance data acquisition systems for such studies have, by necessity, developed in synchrony. However, improvements in sample purification techniques are also required to reveal new phenomena. Here we assessed a cell sorter as a sample-pretreatment tool for a single-cell level assay. A cell sorter is routinely used for selecting one type of cells from a heterogeneous mixture of cells using specific fluorescence labels. In this case, we wanted to select cells of exactly the same size, shape, and cell-cycle stage from a population, without using a specific fluorescence label. Results We used four light scatter parameters: the peak height and area of the forward scatter (FSheight and FSarea and side scatter (SSheight and SSarea. The rat pheochromocytoma PC12 cell line, a neuronal cell line, was used for all experiments. The living cells concentrated in the high FSarea and middle SSheight/SSarea fractions. Single cells without cell clumps were concentrated in the low SS and middle FS fractions, and in the higher FSheight/FSarea and SSheight/SSarea fractions. The cell populations from these viable, single-cell-rich fractions were divided into twelve subfractions based on their FSarea-SSarea profiles, for more detailed analysis. We found that SSarea was proportional to the cell volume and the FSarea correlated with cell roundness and elongation, as well as with the level of DNA in the cell. To test the method and to characterize the basic properties of the isolated single cells, sorted cells were cultured in separate wells. The cells in all subfractions survived, proliferated and differentiated normally, suggesting that there was no serious damage. The smallest, roundest, and smoothest cells had the highest viability. There was no correlation between proliferation and differentiation. NGF increases

  3. Glucosylceramide synthesis inhibition affects cell cycle progression, membrane trafficking, and stage differentiation in Giardia lamblia.

    Science.gov (United States)

    Stefanić, Sasa; Spycher, Cornelia; Morf, Laura; Fabriàs, Gemma; Casas, Josefina; Schraner, Elisabeth; Wild, Peter; Hehl, Adrian B; Sonda, Sabrina

    2010-09-01

    Synthesis of glucosylceramide via glucosylceramide synthase (GCS) is a crucial event in higher eukaryotes, both for the production of complex glycosphingolipids and for regulating cellular levels of ceramide, a potent antiproliferative second messenger. In this study, we explored the dependence of the early branching eukaryote Giardia lamblia on GCS activity. Biochemical analyses revealed that the parasite has a GCS located in endoplasmic reticulum (ER) membranes that is active in proliferating and encysting trophozoites. Pharmacological inhibition of GCS induced aberrant cell division, characterized by arrest of cytokinesis, incomplete cleavage furrow formation, and consequent block of replication. Importantly, we showed that increased ceramide levels were responsible for the cytokinesis arrest. In addition, GCS inhibition resulted in prominent ultrastructural abnormalities, including accumulation of cytosolic vesicles, enlarged lysosomes, and clathrin disorganization. Moreover, anterograde trafficking of the encystations-specific protein CWP1 was severely compromised and resulted in inhibition of stage differentiation. Our results reveal novel aspects of lipid metabolism in G. lamblia and specifically highlight the vital role of GCS in regulating cell cycle progression, membrane trafficking events, and stage differentiation in this parasite. In addition, we identified ceramide as a potent bioactive molecule, underscoring the universal conservation of ceramide signaling in eukaryotes. PMID:20335568

  4. Immunohistochemical study of the expression of cell cycle regulating proteins at different stages of bladder cancer

    DEFF Research Database (Denmark)

    Primdahl, Hanne; Maase, Hans von der; Sørensen, Flemming B.; Wolf, Hans; Ørntoft, Torben Falck

    2002-01-01

    PURPOSE: The cell cycle is known to be deregulated in cancer. We therefore analyzed the expression of the cell cycle related proteins p21, p27, p16, Rb, and L-myc by immunohistochemical staining of bladder tumors. METHODS: The tissue material consisted of bladder tumors from three groups of...

  5. Severe NDE1-mediated microcephaly results from neural progenitor cell cycle arrests at multiple specific stages.

    Science.gov (United States)

    Doobin, David J; Kemal, Shahrnaz; Dantas, Tiago J; Vallee, Richard B

    2016-01-01

    Microcephaly is a cortical malformation disorder characterized by an abnormally small brain. Recent studies have revealed severe cases of microcephaly resulting from human mutations in the NDE1 gene, which is involved in the regulation of cytoplasmic dynein. Here using in utero electroporation of NDE1 short hairpin RNA (shRNA) in embryonic rat brains, we observe cell cycle arrest of proliferating neural progenitors at three distinct stages: during apical interkinetic nuclear migration, at the G2-to-M transition and in regulation of primary cilia at the G1-to-S transition. RNAi against the NDE1 paralogue NDEL1 has no such effects. However, NDEL1 overexpression can functionally compensate for NDE1, except at the G2-to-M transition, revealing a unique NDE1 role. In contrast, NDE1 and NDEL1 RNAi have comparable effects on postmitotic neuronal migration. These results reveal that the severity of NDE1-associated microcephaly results not from defects in mitosis, but rather the inability of neural progenitors to ever reach this stage. PMID:27553190

  6. Influence of irradiation at different stages of mitotic cycle upon production of sister chromatid exchanges in cultured Chinese hamster cells

    International Nuclear Information System (INIS)

    Frequency of sister chromatid exchanges (SCE) and microexchanges in Chinese hamster cells has been studied by means of the method of differential staining of chromatids on irradiation at different stages of the mitotic cycle. It is shown that the irradiation enhances frequency of SCE and microexchanges if it is carried out before the end of DNA replication synthesis. Comparison of frequency depenedence of radiation-induced microexchanges and SCE at different stages of the mitotic cycle results in the conclusion that the microexchanges are none other than small SCE

  7. Influence of irradiation at different stages of mitotic cycle unon production of sister chromatid exchanges in cultured chinese hamster cells

    International Nuclear Information System (INIS)

    Frequency of.sister chromatid exchanges (SCE) and microexchanges in the chinese hamster cells was investigated by means of the method of differential colouring of chromatids on irradiation at different stages of the mitotic cycle. It is shown that the irradiation increases frequency of SCE and microexchanges if it is performed before the end of the replicative DNA synthesis. Comparison of frequency dependence of radiation-induced microexchanges and SCE at different stages of the mitotic cycle permits to conclude that the microexchanges are small SCE

  8. Response to fission neutron irradiation of spermatogonial stem cells in different stages of the cycle of the siminiferous epithelium

    International Nuclear Information System (INIS)

    Mice were irradiated with 1 Gy of fission neutrons. At intervals up to 15 days after irradiation undifferentiated spermatogonia were counted in whole mounts of seminiferous tubules in up to eight stages of the epithelial cycle. From Day 6 onward lower numbers of spermatogonia were found in the area which were in stages IV-VII during irradiation than in those which were in stages IX-II. Minimal numbers in the former area were two to six times lower than those in the latter one. Areas whch were in stage III or VIII gave intermediate values. It is concluded that the epithelial cycle can be divided into two parts with a different response to irradiation, that begin or end in stages III and VIII. Part III-VIII and part VIII-III comprise 45 and 55% of the epithelial cycle, respectively. In part VIII-III control levels were found again at Day 15, while in part III-VIII spermatogonial numbers were still very low. In controls it was found that part VIII-III corresponds to a period of high proliferative activity of the stem cells, while in part III-VIII the proliferative activity is very low. This may affect their radiosensitivity and/or their proliferative behavior after irradiation, resulting in different spermatogonial numbers in the two parts of the epithelial cycle

  9. Murine Wee1 Plays a Critical Role in Cell Cycle Regulation and Pre-Implantation Stages of Embryonic Development

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    Yohei Tominaga, Cuiling Li, Rui-Hong Wang, Chu-Xia Deng

    2006-01-01

    Full Text Available Wee1 kinase regulates the G2/M cell cycle checkpoint by phosphorylating and inactivating the mitotic cyclin-dependent kinase 1 (Cdk1. Loss of Wee1 in many systems, including yeast and drosophila, leads to premature mitotic entry. However, the developmental role of Wee1 in mammals remains unclear. In this study, we established Wee1 knockout mice by gene targeting. We found that Wee-/- embryos were defective in the G2/M cell cycle checkpoint induced by γ-irradiation and died of apoptosis before embryonic (E day 3.5. To study the function of Wee1 further, we have developed MEF cells in which Wee1 is disrupted by a tamoxifen inducible Cre-LoxP approach. We found that acute deletion of Wee1 resulted in profound growth defects and cell death. Wee1 deficient cells displayed chromosome aneuploidy and DNA damage as revealed by γ-H2AX foci formation and Chk2 activation. Further studies revealed a conserved mechanism of Wee1 in regulating mitotic entry and the G2/M checkpoint compared with other lower organisms. These data provide in vivo evidence that mammalian Wee1 plays a critical role in maintaining genome integrity and is essential for embryonic survival at the pre-implantation stage of mouse development.

  10. Glucosylceramide synthesis inhibition affects cell cycle progression, membrane trafficking, and stage differentiation in Giardia lamblia[S

    Science.gov (United States)

    Štefanić, Saša; Spycher, Cornelia; Morf, Laura; Fabriàs, Gemma; Casas, Josefina; Schraner, Elisabeth; Wild, Peter; Hehl, Adrian B.; Sonda, Sabrina

    2010-01-01

    Synthesis of glucosylceramide via glucosylceramide synthase (GCS) is a crucial event in higher eukaryotes, both for the production of complex glycosphingolipids and for regulating cellular levels of ceramide, a potent antiproliferative second messenger. In this study, we explored the dependence of the early branching eukaryote Giardia lamblia on GCS activity. Biochemical analyses revealed that the parasite has a GCS located in endoplasmic reticulum (ER) membranes that is active in proliferating and encysting trophozoites. Pharmacological inhibition of GCS induced aberrant cell division, characterized by arrest of cytokinesis, incomplete cleavage furrow formation, and consequent block of replication. Importantly, we showed that increased ceramide levels were responsible for the cytokinesis arrest. In addition, GCS inhibition resulted in prominent ultrastructural abnormalities, including accumulation of cytosolic vesicles, enlarged lysosomes, and clathrin disorganization. Moreover, anterograde trafficking of the encystations-specific protein CWP1 was severely compromised and resulted in inhibition of stage differentiation. Our results reveal novel aspects of lipid metabolism in G. lamblia and specifically highlight the vital role of GCS in regulating cell cycle progression, membrane trafficking events, and stage differentiation in this parasite. In addition, we identified ceramide as a potent bioactive molecule, underscoring the universal conservation of ceramide signaling in eukaryotes. PMID:20335568

  11. Effect of kinetin on the course of cell cycle in successive developmental stages of the antheridial filaments of Chara vulgaris L.

    Directory of Open Access Journals (Sweden)

    Mirosław Godlewski

    2014-02-01

    Full Text Available Effects of kinetin on the course of cell cycle in successive developmental stages of the antheridial filaments of Chara vulgaris L. were investigated. A shortening of the duration of cell cycles has been observed, particularly in initial. and final developmental stages. S phase. shortened in all stages whereas G2 phase+mitosis shortened in early but become longer in late developmental stages of filaments. Incorporation of 14C-adenine into cell nuclei increased after kinetin treatment in 4- and 8-celled filaments whereas that of 3H-phenylalanine increased in 8- and particularly 16-celled ones. This plant growth regulator stimulated also the 3H-thymidine incorporation into cells in studied developmental stages of filaments. The stimulation of radioactive phenylalanine incorporation into nucleus and cytoplasm was stronger in late G2 phase. A participation of cytokinins in the control of cell cycle in relation to process of differentiation of antheridial cells is discussed. A possibility of changes in the cytokinin content in antheridia and antheridial filament cells during their; development has been postulated.

  12. The retinoblastoma-susceptibility gene product becomes phosphorylated in multiple stages during cell cycle entry and progression.

    OpenAIRE

    DeCaprio, J A; Furukawa, Y.; Ajchenbaum, F; Griffin, J D; Livingston, D M

    1992-01-01

    The retinoblastoma-susceptibility gene product (RB) undergoes cell cycle-dependent phosphorylation and dephosphorylation. We characterized RB phosphorylation after mitogenic stimulation of primary human T lymphocytes, initially arrested in the G0 state. RB is phosphorylated in at least three steps when T cells are driven into the cell cycle. The first event occurs during mid G1 phase, the second during S phase, and the third in G2/M. Tryptic phosphopeptide mapping indicates that the different...

  13. Measurement of X-ray-induced DNA double-strand breaks at various stages of the cell cycle using the total fluorescence as a comet assay parameter

    International Nuclear Information System (INIS)

    The aim of the study was to develop a protocol for both estimating cell cycle position and the level of ionizing radiation-induced DNA dsb using the neutral comet assay. Using DNA histograms, cell cycle positions were determined for human dermal fibroblasts. The tail intensity was used to estimate the level of DNA damage induced by X-rays, at different positions of the cell cycle. The results of tail intensity versus DNA content bivariate analysis of exponentially growing cells showed a remarkable decrease in tail intensity with transition of cells from G1 to S-phase and increases slightly with transition to G2/M phase. This effect is observed at all doses including unirradiated cells, indicating that the effect is not caused by X-rays and the comet assay based on the current tail parameters is not relevant to measure DNA damage at various stages of the cell cycle. The results of dose response curves showed a linear decrease in the comet fluorescence with the X-ray dose. This observation provides a basis for estimating the fraction of damaged DNA, based on the fluorescence decrement induced by ionizing radiation. The results of this new approach showed a linear increase in DNA damage with dose, at various stages of the cell cycle, with rates, which vary in the following order G0>G2/M>S/G1 cells. These results suggest that G0 and G2/M cells are the most sensitive to X-rays among all phases of the cell cycle and suggest synchronization of cells at these phases to increase the cellular radiosensitivity during radiotherapy. - Display Omitted Highlights: → Increase in DNA damage with dose. → Introduction of a new technique for measuring DNA damage using a new approach of the neutral comet assay. → Estimation of DNA damage in mammalian cells.

  14. Measurement of X-ray-induced DNA double-strand breaks at various stages of the cell cycle using the total fluorescence as a comet assay parameter

    Energy Technology Data Exchange (ETDEWEB)

    Attia, Atef M.M. [Department of Biochemistry, Biophysical laboratory, National Research Center, Dokki, Cairo (Egypt); Nabil, Ghada M., E-mail: gmnabilnooh@hotmail.com [Department of Biochemistry, Biophysical laboratory, National Research Center, Dokki, Cairo (Egypt); Frankenberg, Dieter; Frankenberg-Schwager, M. [Abteilung Klinische Strahlenbiologie und Klinische Strahlenphysik, Zentrum, Radiologie, Georg-August-Universitaet Goettingen, Von-Siebold-Str.3 (Germany)

    2011-11-15

    The aim of the study was to develop a protocol for both estimating cell cycle position and the level of ionizing radiation-induced DNA dsb using the neutral comet assay. Using DNA histograms, cell cycle positions were determined for human dermal fibroblasts. The tail intensity was used to estimate the level of DNA damage induced by X-rays, at different positions of the cell cycle. The results of tail intensity versus DNA content bivariate analysis of exponentially growing cells showed a remarkable decrease in tail intensity with transition of cells from G1 to S-phase and increases slightly with transition to G2/M phase. This effect is observed at all doses including unirradiated cells, indicating that the effect is not caused by X-rays and the comet assay based on the current tail parameters is not relevant to measure DNA damage at various stages of the cell cycle. The results of dose response curves showed a linear decrease in the comet fluorescence with the X-ray dose. This observation provides a basis for estimating the fraction of damaged DNA, based on the fluorescence decrement induced by ionizing radiation. The results of this new approach showed a linear increase in DNA damage with dose, at various stages of the cell cycle, with rates, which vary in the following order G0>G2/M>S/G1 cells. These results suggest that G0 and G2/M cells are the most sensitive to X-rays among all phases of the cell cycle and suggest synchronization of cells at these phases to increase the cellular radiosensitivity during radiotherapy. - Display Omitted Highlights: > Increase in DNA damage with dose. > Introduction of a new technique for measuring DNA damage using a new approach of the neutral comet assay. > Estimation of DNA damage in mammalian cells.

  15. Measurement of X-ray-induced DNA double-strand breaks at various stages of the cell cycle using the total fluorescence as a comet assay parameter

    Science.gov (United States)

    Attia, Atef M. M.; Nabil, Ghada M.; Frankenberg, Dieter; Frankenberg-Schwager, M.

    2011-11-01

    The aim of the study was to develop a protocol for both estimating cell cycle position and the level of ionizing radiation-induced DNA dsb using the neutral comet assay. Using DNA histograms, cell cycle positions were determined for human dermal fibroblasts. The tail intensity was used to estimate the level of DNA damage induced by X-rays, at different positions of the cell cycle. The results of tail intensity versus DNA content bivariate analysis of exponentially growing cells showed a remarkable decrease in tail intensity with transition of cells from G1 to S-phase and increases slightly with transition to G2/M phase. This effect is observed at all doses including unirradiated cells, indicating that the effect is not caused by X-rays and the comet assay based on the current tail parameters is not relevant to measure DNA damage at various stages of the cell cycle. The results of dose response curves showed a linear decrease in the comet fluorescence with the X-ray dose. This observation provides a basis for estimating the fraction of damaged DNA, based on the fluorescence decrement induced by ionizing radiation. The results of this new approach showed a linear increase in DNA damage with dose, at various stages of the cell cycle, with rates, which vary in the following order G0>G2/M>S/G1 cells.These results suggest that G0 and G2/M cells are the most sensitive to X-rays among all phases of the cell cycle and suggest synchronization of cells at these phases to increase the cellular radiosensitivity during radiotherapy.

  16. Role of bromodeoxyuridine in the formation of SCE after γ-irradiation of human lymphocytes at the presynthetic stage of the cell cycle

    International Nuclear Information System (INIS)

    The formation of SCE was studied in human lymphocytes irradiated at the presynthetic stage of the cell cycle in the presence or absence of 5-bromodeoxyuridine. The results obtained showed that 5-bromodeoxyuridine present in the cultur medium at the time of exposure or during the postirradiation period increased the yield of SCE. It is suggested that 5-bromodeoxyuridine exerts its effect through interfering with DNA repair

  17. Consumer Debt Delinquency over Life Cycle Stages

    OpenAIRE

    Jing Jian Xiao; Rui Yao

    2011-01-01

    Consumer debt delinquency, as measured by being 60 or more days late in in debt payment, is an indicator of financial ill health. Using six datasets of the 1992-2007 U.S. Surveys of Consumer Finances, this study examines consumer debt delinquency over life cycle stages. Inspired by previous research (Du & Kamakura, 2006), fifteen life cycle stages are defined by household head’s age, marital status, and presence and age of children. Multivariate logistic results show that young couples status...

  18. Isolation of Plant Nuclei at Defined Cell Cycle Stages Using EdU Labeling and Flow Cytometry.

    Science.gov (United States)

    Wear, Emily E; Concia, Lorenzo; Brooks, Ashley M; Markham, Emily A; Lee, Tae-Jin; Allen, George C; Thompson, William F; Hanley-Bowdoin, Linda

    2016-01-01

    5-Ethynyl-2'-deoxyuridine (EdU) is a nucleoside analog of thymidine that can be rapidly incorporated into replicating DNA in vivo and, subsequently, detected by using "click" chemistry to couple its terminal alkyne group to fluorescent azides such as Alexa Fluor 488. Recently, EdU incorporation followed by coupling with a fluorophore has been used to visualize newly synthesized DNA in a wide range of plant species. One particularly useful application is in flow cytometry, where two-parameter sorting can be employed to analyze different phases of the cell cycle, as defined both by total DNA content and the amount of EdU pulse-labeled DNA. This approach allows analysis of the cell cycle without the need for synchronous cell populations, which can be difficult to obtain in many plant systems. The approach presented here, which was developed for fixed, EdU-labeled nuclei, can be used to prepare analytical profiles as well as to make highly purified preparations of G1, S, or G2/M phase nuclei for molecular or biochemical analysis. We present protocols for EdU pulse labeling, tissue fixation and harvesting, nuclei preparation, and flow sorting. Although developed for Arabidopsis suspension cells and maize root tips, these protocols should be modifiable to many other plant systems. PMID:26659955

  19. Disruptive cell cycle regulation involving epigenetic downregulation of Cdkn2a (p16Ink4a) in early-stage liver tumor-promotion facilitating liver cell regeneration in rats

    International Nuclear Information System (INIS)

    Cell cycle aberration was immunohistochemically examined in relation to preneoplastic liver cell foci expressing glutathione S-transferase placental form (GST-P) at early stages of tumor-promotion in rats with thioacetamide (TAA), a hepatocarcinogen facilitating liver cell regeneration. Immunoexpression of p16Ink4a following exposure to other hepatocarcinogens/promoters and its DNA methylation status were also analyzed during early and late tumor-promotion stages. GST-P+ liver cell foci increased cell proliferation and decreased apoptosis when compared with surrounding liver cells. In concordance with GST-P+ foci, checkpoint proteins at G1/S (p21Cip1, p27Kip1 and p16Ink4a) and G2/M (phospho-checkpoint kinase 1, Cdc25c and phospho-Wee1) were either up- or downregulated. Cellular distribution within GST-P+ foci was either increased or decreased with proteins related to G2-M phase or DNA damage (topoisomerase IIα, phospho-histone H2AX, phospho-histone H3 and Cdc2). In particular, p16Ink4a typically downregulated in GST-P+ foci and regenerative nodules at early tumor-promotion stage with hepatocarcinogens facilitating liver cell regeneration and in neoplastic lesions at late tumor-promotion stage with hepatocarcinogens/promoters irrespective of regenerating potential. Hypermethylation at exon 2 of Cdkn2a was detected at both early- and late-stages. Thus, diverse disruptive expression of G1/S and G2/M proteins, which allows for clonal selection of GST-P+ foci, results in the acquisition of multiple aberrant phenotypes to disrupt checkpoint function. Moreover, increased DNA-damage responses within GST-P+ foci may be the signature of genetic alterations. Intraexonic hypermethylation may be responsible for p16Ink4a-downregulation, which facilitates cell cycle progression in early preneoplastic lesions produced by repeated cell regeneration and late-stage neoplastic lesions irrespective of the carcinogenic mechanism.

  20. Loss of Expression of Reprimo, a p53-induced Cell Cycle Arrest Gene, Correlates with Invasive Stage of Tumor Progression and p73 Expression in Gastric Cancer.

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    Kathleen Saavedra

    Full Text Available Reprimo (RPRM, a downstream effector of p53-induced cell cycle arrest at G2/M, has been proposed as a putative tumor suppressor gene (TSG and as a potential biomarker for non-invasive detection of gastric cancer (GC. The aim of this study was to evaluate the epigenetic silencing of RPRM gene by promoter methylation and its tumor suppressor function in GC cell lines. Furthermore, clinical significance of RPRM protein product and its association with p53/p73 tumor suppressor protein family was explored. Epigenetic silencing of RPRM gene by promoter methylation was evaluated in four GC cell lines. Protein expression of RPRM was evaluated in 20 tumor and non-tumor matched cases. The clinical significance of RPRM association with p53/p73 tumor suppressor protein family was assessed in 114 GC cases. Tumor suppressor function was examined through functional assays. RPRM gene expression was negatively correlated with promoter methylation (Spearman rank r = -1; p = 0.042. RPRM overexpression inhibited colony formation and anchorage-independent growth. In clinical samples, RPRM gene protein expression was detected in 75% (15/20 of non-tumor adjacent mucosa, but only in 25% (5/20 of gastric tumor tissues (p = 0.001. Clinicopathological correlations of loss of RPRM expression were significantly associated with invasive stage of GC (stage I to II-IV, p = 0.02 and a positive association between RPRM and p73 gene protein product expression was found (p<0.0001 and kappa value = 0.363. In conclusion, epigenetic silencing of RPRM gene by promoter methylation is associated with loss of RPRM expression. Functional assays suggest that RPRM behaves as a TSG. Loss of expression of RPRM gene protein product is associated with the invasive stage of GC. Positive association between RPRM and p73 expression suggest that other members of the p53 gene family may participate in the regulation of RPRM expression.

  1. Role of Artemis in DSB repair and guarding chromosomal stability following exposure to ionizing radiation at different stages of cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Darroudi, Firouz [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands)]. E-mail: F.Darroudi@LUMC.NL; Wiegant, Wouter [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Meijers, Matty [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Friedl, Anna A. [Radiobiological Institute, University of Munich, Munich (Germany); Institute of Radiobiology, GSF National Research Center for Environment and Health, Neuherberg (Germany); Burg, Mirjam van der [Department of Immunology, Erasmus Medical Centre, Rotterdam (Netherlands); Fomina, Janna [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Dongen, Jacques J.M. van [Department of Immunology, Erasmus Medical Centre, Rotterdam (Netherlands); Gent, Dik C. van [Department of Cell Biology and Genetics, Erasmus Medical Centre, Rotterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Department of Molecular Cell Genetics, Collegium Medicum, N. Corpernicus University, Bydgoszcz (Poland)

    2007-02-03

    We analyzed the phenotype of cells derived from SCID patients with different mutations in the Artemis gene. Using clonogenic survival assay an increased sensitivity was found to X-rays (2-3-fold) and bleomycin (2-fold), as well as to etoposide, camptothecin and methylmethane sulphonate (up to 1.5-fold). In contrast, we did not find increased sensitivity to cross-linking agents mitomycin C and cis-platinum. The kinetics of DSB repair assessed by pulsed-field gel electrophoresis and {gamma}H2AX foci formation after ionizing irradiation, indicate that 15-20% of DSB are not repaired in Artemis-deficient cells. In order to get a better understanding of the repair defect in Artemis-deficient cells, we studied chromosomal damage at different stages of the cell cycle. In contrast to AT cells, Artemis-deficient cells appear to have a normal G{sub 1}/S-block that resulted in a similar frequency of dicentrics and translocations, however, frequency of acentrics fragments was found to be 2-4-fold higher compared to normal fibroblasts. Irradiation in G{sub 2} resulted in a higher frequency of chromatid-type aberrations (1.5-3-fold) than in normal cells, indicating that a fraction of DSB requires Artemis for proper repair. Our data are consistent with a function of Artemis protein in processing of a subset of complex DSB, without G{sub 1} cell cycle checkpoint defects. This type of DSB can be induced in high proportion and persist through S-phase and in part might be responsible for the formation of chromatid-type exchanges in G{sub 1}-irradiated Artemis-deficient cells. Among different human radiosensitive fibroblasts studied for endogenous (in untreated samples) as well as X-ray-induced DNA damage, the ranking order on the basis of higher incidence of spontaneously occurring chromosomal alterations and induced ones was: ligase 4 {>=} AT > Artemis. This observation implicates that in human fibroblasts following exposure to ionizing radiation a lower risk might be created when

  2. Determining the Stage of the Estrous Cycle in Female Mice by Vaginal Smear.

    Science.gov (United States)

    Gonzalez, Gabriel

    2016-01-01

    Female mice undergo a 3- to 5-d, hormonally controlled estrous cycle. The estrous cycle is divided into different stages, including diestrus, proestrus, estrus, and metestrus. These stages can easily be determined by examining washes or cell smears of the vagina. Determining the stage of the estrous cycle may be important for setting up matings, identifying receptive females for artificial insemination, and analyzing phenotypes of the female reproductive tract. PMID:27480723

  3. Effects of food nutrient content, insect age and stage in the feeding cycle on the FMRFamide immunoreactivity of diffuse endocrine cells in the locust gut

    OpenAIRE

    Zudaire, E. (Enrique); Simpson, S J; Montuenga, L M

    1998-01-01

    We have studied the influence of variations in dietary protein and digestible carbohydrate content, of insect age and of time during the feeding cycle on the endocrine cells of the ampullar region of the midgut in the African migratory locust Locusta migratoria L. Morphometric analysis of FMRFamide-like immunoreactivity was used as an indirect measure of the amount of FMRFamide-related peptides (FaRPs) stored in the gut endocrine cells. There was a highly significant correlation between FaRP ...

  4. Interferometric measurements of dry mass content in nuclei and cytoplasm in the life cycle of antheridial filaments cells of Chara vulgaris L. in their successive developmental stages

    Directory of Open Access Journals (Sweden)

    Hanna Kuran

    2015-05-01

    Full Text Available Interferometric measurements of the nucleus and cytoplasm dry mass during interphase in the successive stages of development of antheridial filaments of Chara vulgaris demonstrated that the dry mass and surface area of cell nuclei double in size in each of the successive generations of the filaments, whereas neither the surface nor the dry mass of the cytoplasm increase in such proportion in the same period. In the successive stages of development of the antheridial filaments the dry mass and surface area of the nuclei and cytoplasm gradually diminish.

  5. The genetic covariance between life cycle stages separated by metamorphosis

    OpenAIRE

    Aguirre, J. David; Blows, Mark W.; Dustin J Marshall

    2014-01-01

    Metamorphosis is common in animals, yet the genetic associations between life cycle stages are poorly understood. Given the radical changes that occur at metamorphosis, selection may differ before and after metamorphosis, and the extent that genetic associations between pre- and post-metamorphic traits constrain evolutionary change is a subject of considerable interest. In some instances, metamorphosis may allow the genetic decoupling of life cycle stages, whereas in others, metamorphosis cou...

  6. Two-stage, self-cycling process for the production of bacteriophages

    Directory of Open Access Journals (Sweden)

    Cooper David G

    2010-11-01

    Full Text Available Abstract Background A two-stage, self-cycling process for the production of bacteriophages was developed. The first stage, containing only the uninfected host bacterium, was operated under self-cycling fermentation (SCF conditions. This automated method, using the derivative of the carbon dioxide evolution rate (CER as the control parameter, led to the synchronization of the host bacterium. The second stage, containing both the host and the phage, was operated using self-cycling infection (SCI with CER and CER-derived data as the control parameters. When each infection cycle was terminated, phages were harvested and a new infection cycle was initiated by adding host cells from the SCF (first stage. This was augmented with fresh medium and the small amount of phages left from the previous cycle initiated the next infection cycle. Both stages were operated independently, except for this short period of time when the SCF harvest was added to the SCI to initiate the next cycle. Results It was demonstrated that this mode of operation resulted in stable infection cycles if the growth of the host cells in the SCF was synchronized. The final phage titers obtained were reproducible among cycles and were as good as those obtained in batch productions performed under the same conditions (medium, temperature, initial multiplicity of infection, etc.. Moreover, phages obtained in different cycles showed no important difference in infectivity. Finally, it was shown that cell synchronization of the host cells in the first stage (SCF not only maintained the volumetric productivity (phages per volume but also led to higher specific productivity (phage per cell per hour in the second stage (SCI. Conclusions Production of bacteriophage T4 in the semi-continuous, automated SCF/SCI system was efficient and reproducible from cycle to cycle. Synchronization of the host in the first stage prior to infection led to improvements in the specific productivity of phages in

  7. Early stage fuel cell funding

    International Nuclear Information System (INIS)

    'Full text:' Early stage venture funding requires an in depth understanding of both current and future markets as well as the key technical hurdles that need to be overcome for new technology to commercialize into successful products for mass markets. As the leading fuel cell and hydrogen investor, Chrysalix continuously reviews global trends and new technologies, evaluates them with industry leaders worldwide and tries to match them up with the best possible management teams when selecting its early stage investments. Chrysalix Energy Limited Partnership is an early-stage venture capital firm focusing on fuel cell and related fueling technology companies and is a private equity joint venture between Ballard Power Systems, BASF Venture Capital, The BOC Group, The Boeing Company, Duke Energy, Mitsubishi Corporation and Shell Hydrogen. Operating independently, Chrysalix offers a unique value proposition to its clients throughout the business planning, start-up and operations phases of development. Chrysalix provides early-stage funding to new companies as well as management assistance, technological knowledge, organized networking with industry players and experience in the management of intellectual property. (author)

  8. Modelling and Simulation of a Two-Stage Refrigeration Cycle

    OpenAIRE

    Verheyleweghen, Adriaen

    2015-01-01

    A two-stage refrigeration cycle was modelled and optimized in MATLAB. The optimum was found to be very flat, resulting in small losses from disturbances and implementation errors. The two unconstrained degrees of freedom were used to implement self-optimizing controllers. A subset of five measurements was used for the self-optimizing controller since this gave reasonably small losses. The controllers assured optimal steady-state operation of the refrigeration cycle even when disturbed. Studie...

  9. MAPK uncouples cell cycle progression from cell spreading and cytoskeletal organization in cycling cells

    OpenAIRE

    Margadant, Coert; Cremers, Lobke; Sonnenberg, Arnoud; Boonstra, Johannes

    2012-01-01

    Integrin-mediated cytoskeletal tension supports growth-factor-induced proliferation, and disruption of the actin cytoskeleton in growth factor-stimulated cells prevents the re-expression of cyclin D and cell cycle re-entry from quiescence. In contrast to cells that enter the cell cycle from G0, cycling cells continuously express cyclin D, and are subject to major cell shape changes during the cell cycle. Here, we investigated the cell cycle requirements for cytoskeletal tension and cell sprea...

  10. Cell cycle control in Alphaproteobacteria.

    Science.gov (United States)

    Collier, Justine

    2016-04-01

    Alphaproteobacteria include many medically and environmentally important organisms. Despite the diversity of their niches and lifestyles, from free-living to host-associated, they usually rely on very similar mechanisms to control their cell cycles. Studies on Caulobacter crescentus still lay the foundation for understanding the molecular details of pathways regulating DNA replication and cell division and coordinating these two processes with other events of the cell cycle. This review highlights recent discoveries on the regulation and the mode of action of conserved global regulators and small molecules like c-di-GMP and (p)ppGpp, which play key roles in cell cycle control. It also describes several newly identified mechanisms that modulate cell cycle progression in response to stresses or environmental conditions. PMID:26871482

  11. Alteration of cell cycle progression by Sindbis virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Ruirong; Saito, Kengo [Department of Molecular Virology, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan); Isegawa, Naohisa [Laboratory Animal Center, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan); Shirasawa, Hiroshi, E-mail: sirasawa@faculty.chiba-u.jp [Department of Molecular Virology, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan)

    2015-07-10

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.

  12. Stage-by-Stage and Parallel Flow Path Compressor Modeling for a Variable Cycle Engine

    Science.gov (United States)

    Kopasakis, George; Connolly, Joseph W.; Cheng, Larry

    2015-01-01

    This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design.

  13. The one-cell mouse embryo: cell cycle-dependent radiosensitivity and development of chromosomal anomalies in postradiation cell cycles

    International Nuclear Information System (INIS)

    One-cell mouse embryos were irradiated with X-rays at different cell cycle stages. Examination of structural chromosomal anomalies and micronucleus formation in postradiation mitoses and interphases demonstrated cell cycle-dependent radiosensitivities in the order: late G2 phase > G1 phase > S phase > early G2 phase > stage of decondensing nuclei. Comparison of the quality and quantity of chromosomal aberrations from the first to third mitosis led to the conclusion that new chromosomal anomalies were formed in the course of postirradiation cell cycles. This hypothesis was supported by an increasing number of micronuclei from 24 to 48 h post-conception. In addition to structural chromosomal aberrations, radiation-induced chromosome loss was observed with a frequency that was obviously independent of the exposed cell cycle phase. Loss of acentric chromosome fragments and of single chromosomes contributed to the micronucleus formation. (author)

  14. Household Life-Cycle Stages, Transitions, and Product Expenditures.

    OpenAIRE

    Wilkes, Robert E

    1995-01-01

    Data from the U.S. Bureau of Labor Statistics' Consumer Expenditure Survey provide empirical verification of changes in household spending across a wide variety of products as households pass from one stage of the household life cycle to another. Three spending patterns emerged: (1) a generalized inverted U pattern, with spending rising sharply as households shift from young single to young married, then remaining relatively high, and falling sharply at the older married and/or older single s...

  15. Two-stage fuel cycles with accelerator-driven systems

    International Nuclear Information System (INIS)

    As part of ongoing efforts to assess nuclear fuel cycle options, four fuel cycle options based on the same two reactor technologies have been studied. All four options are composed of two stages, one which contains pressurized-water reactors (PWRs), and the other, fast spectrum accelerator-driven systems (ADS). The performance characteristics and material mass flows have been determined for the fuel cycle options considered, and compared. The three major difficulties encountered when modeling and analyzing these fuel cycle options have been to maintain the PWR fuel temperature reactivity coefficient negative when multi-recycling MOX fuel, to design the ADS core to be a breeder, and to achieve a high enough keff in the ADS to avoid the accelerator power consumption to be larger than the power generated by the ADS core. The differences observed in the performance characteristics and mass flows between the four fuel cycle options analyzed are discussed in this paper. Overall it is found that despite the four fuel cycle options being based on the same reactor technologies and seemingly similar at first sight, they perform differently and offer different features: resource utilization, need for uranium enrichment, required reprocessing capacity, and material type to be stored. (author)

  16. Measurement of DNA double-strand breaks in CHO cells at various stages of the cell cycle using pulsed field gel electrophoresis: calibration by means of 125I decay

    International Nuclear Information System (INIS)

    Experiments were performed to calibrate a recently developed pulsed field gel electrophoresis assay, the asymmetric field inversion gel electrophoresis (AFIGE), for the measurement of double-strand breaks (dsb) in the DNA of mammalian cells. Calibration was carried out by means of 125I decay accumulation, under conditions preventing repair, based on the observation that each 125I decay in the DNA produces approximately one dsb. Results suggest that that observed fluctuations in the fraction of DNA activity released (FAR) per Gy throughout the cycle reflect cell-cycle-associated differences in the physicochemical properties of the DNA molecules that alter their electrophoretic mobility, rather than variations in the induction of dsb per Gy, i.e. the sensitivity of the assay fluctuates throughout the cycle. (author)

  17. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

  18. Medical Care Use and Expenditures for Children across Stages of the Family Life Cycle.

    Science.gov (United States)

    Cunningham, Peter J.

    1990-01-01

    Investigated differences in use of and expenditures for children's health services across stages of family life cycle and how family characteristics affected medical care use and expenditures for children differently, depending on family life cycle stage. Found variation across family life cycle stages in terms of children's mean number of…

  19. Modulation of Golgi-associated microtubule nucleation throughout the cell cycle

    OpenAIRE

    Maia, Ana Rita Ramada; Zhu, Xiaodong; Miller, Paul; Gu, Guoqiang; Maiato, Helder; Kaverina, Irina

    2013-01-01

    A microtubule (MT) sub-population that emanates from Golgi membrane has been recently shown to comprise a significant part of MT network in interphase cells. In this study, we address whether Golgi membrane, which is being extensively remodeled throughout the cell cycle, retains its ability to nucleate MTs at diverse cell cycle stages. Live cell imaging and immunofluorescence microscopy reveals that Golgi-derived MTs form at multiple stages of the cell cycle, including G1, G2 and distinct pha...

  20. Epigenetic dynamics across the cell cycle

    DEFF Research Database (Denmark)

    Kheir, Tony Bou; Lund, Anders H.

    2010-01-01

    Progression of the mammalian cell cycle depends on correct timing and co-ordination of a series of events, which are managed by the cellular transcriptional machinery and epigenetic mechanisms governing genome accessibility. Epigenetic chromatin modifications are dynamic across the cell cycle...... a correct inheritance of epigenetic chromatin modifications to daughter cells. In this chapter, we summarize the current knowledge on the dynamics of epigenetic chromatin modifications during progression of the cell cycle....

  1. A cell-cycle-stage-related chromosomal X-ray hypersensitivity in larval neuroblasts of Drosophila mei-9 and mei 41 mutants suggesting defective DNA double-strand break repair

    International Nuclear Information System (INIS)

    The authors have examined the chromosomal X-ray hypersensitivity in relation to the cell cycle in larval neuroblasts of the mutagen-sensitive and excision repair-defective mutant mei-9 and of the mutagen-sensitive and post-replication repair-defective mutant mei-41 of Drosophila melanogaster. When compared to wild-type cells, cells bearing the mei-9L1 allele produced unusually high levels in particular of chromatid deletions and to a lesser extent also of isochromatid deletions, but virtually no exchange aberrations. The chromosomal hypersensitivity is apparent at M1 when cells are irradiated in S or G2 but not when irradiated in G1. On the other hand, following irradiation cells bearing the mei-41D5 allele predominantly produce chromosome deletions. The phases of major sensitivity are the S and G1. Mei-9 and mei-41 mutants have been classified to date as proficient in DNA double-strand break repair. The data presented in this paper revealed an S-independent clastogenic hypersensitivity of mei-9 and mei-41 cells. They are interpreted as indicative evidence for the presence of impaired DNA double-strand break repair. The cell-cycle-related difference in the ratio of chromatid- versus chromosome-type deletions in both mutants suggests repair defects at partially different phases of the cell cycle in mei-9 and mei-41 mutant cells. (author). 47 refs.; 2 figs.; 5 tabs

  2. Notch signaling regulates late-stage epidermal differentiation and maintains postnatal hair cycle homeostasis.

    Directory of Open Access Journals (Sweden)

    Hsien-Yi Lin

    Full Text Available BACKGROUND: Notch signaling involves ligand-receptor interactions through direct cell-cell contact. Multiple Notch receptors and ligands are expressed in the epidermis and hair follicles during embryonic development and the adult stage. Although Notch signaling plays an important role in regulating differentiation of the epidermis and hair follicles, it remains unclear how Notch signaling participates in late-stage epidermal differentiation and postnatal hair cycle homeostasis. METHODOLOGY AND PRINCIPAL FINDINGS: We applied Cre/loxP system to generate conditional gene targeted mice that allow inactivation of critical components of Notch signaling pathway in the skin. Rbpj, the core component of all four Notch receptors, and Pofut1, an essential factor for ligand-receptor interactions, were inactivated in hair follicle lineages and suprabasal layer of the epidermis using the Tgfb3-Cre mouse line. Rbpj conditional inactivation resulted in granular parakeratosis and reactive epidermal hyperplasia. Pofut1 conditional inactivation led to ultrastructural abnormalities in the granular layer and altered filaggrin processing in the epidermis, suggesting a perturbation of the granular layer differentiation. Disruption of Pofut1 in hair follicle lineages resulted in aberrant telogen morphology, a decrease of bulge stem cell markers, and a concomitant increase of K14-positive keratinocytes in the isthmus of mutant hair follicles. Pofut1-deficent hair follicles displayed a delay in anagen re-entry and dysregulation of proliferation and apoptosis during the hair cycle transition. Moreover, increased DNA double stand breaks were detected in Pofut1-deficent hair follicles, and real time PCR analyses on bulge keratinocytes isolated by FACS revealed an induction of DNA damage response and a paucity of DNA repair machinery in mutant bulge keratinocytes. SIGNIFICANCE: our data reveal a role for Notch signaling in regulating late-stage epidermal differentiation

  3. Assaying Cell Cycle Status Using Flow Cytometry.

    Science.gov (United States)

    Kim, Kang Ho; Sederstrom, Joel M

    2015-01-01

    In this unit, two protocols are described for analyzing cell cycle status using flow cytometry. The first is based on the simultaneous analysis of proliferation-specific marker (Ki-67) and cellular DNA content, which discriminate resting/quiescent cell populations (G0 cell) and quantify cell cycle distribution (G1, S, or G2/M), respectively. The second is based on differential staining of DNA and RNA through co-staining of Hoechst 33342 and Pyronin Y, which is also useful to identify G0 cells from G1 cells. Along with these methods for analyzing cell cycle status, two additional methods for cell proliferation assays with recent updates of newly developed fluorophores, which allow multiplex analysis of cell cycle status, cell proliferation, and a gene of interest using flow cytometry, are outlined. PMID:26131851

  4. Cell cycle and cell signal transduction in marine phytoplankton

    Institute of Scientific and Technical Information of China (English)

    LIU Jingwen; JIAO Nianzhi; CAI Huinong

    2006-01-01

    As unicellular phytoplankton, the growth of a marine phytoplankton population results directly from the completion of a cell cycle, therefore, cell-environment communication is an important way which involves signal transduction pathways to regulate cell cycle progression and contribute to growth, metabolism and primary production and respond to their surrounding environment in marine phytoplankton. Cyclin-CDK and CaM/Ca2+ are essentially key regulators in control of cell cycle and signal transduction pathway, which has important values on both basic research and applied biotechnology. This paper reviews progress made in this research field, which involves the identification and characterization of cyclins and cell signal transduction system, cell cycle control mechanisms in marine phytoplankton cells, cell cycle proteins as a marker of a terminal event to estimate the growth rate of phytoplankton at the species level, cell cycle-dependent toxin production of toxic algae and cell cycle progression regulated by environmental factors.

  5. Impact of the cell division cycle on gene circuits

    Science.gov (United States)

    Bierbaum, Veronika; Klumpp, Stefan

    2015-12-01

    In growing cells, protein synthesis and cell growth are typically not synchronous, and, thus, protein concentrations vary over the cell division cycle. We have developed a theoretical description of genetic regulatory systems in bacteria that explicitly considers the cell division cycle to investigate its impact on gene expression. We calculate the cell-to-cell variations arising from cells being at different stages in the division cycle for unregulated genes and for basic regulatory mechanisms. These variations contribute to the extrinsic noise observed in single-cell experiments, and are most significant for proteins with short lifetimes. Negative autoregulation buffers against variation of protein concentration over the division cycle, but the effect is found to be relatively weak. Stronger buffering is achieved by an increased protein lifetime. Positive autoregulation can strongly amplify such variation if the parameters are set to values that lead to resonance-like behaviour. For cooperative positive autoregulation, the concentration variation over the division cycle diminishes the parameter region of bistability and modulates the switching times between the two stable states. The same effects are seen for a two-gene mutual-repression toggle switch. By contrast, an oscillatory circuit, the repressilator, is only weakly affected by the division cycle.

  6. Biopsy of human morula-stage embryos: outcome of 215 IVF/ICSI cycles with PGS.

    Directory of Open Access Journals (Sweden)

    Elena E Zakharova

    Full Text Available Preimplantation genetic diagnosis (PGD is commonly performed on biopsies from 6-8-cell-stage embryos or blastocyst trophectoderm obtained on day 3 or 5, respectively. Day 4 human embryos at the morula stage were successfully biopsied. Biopsy was performed on 709 morulae from 215 ICSI cycles with preimplantation genetic screening (PGS, and 3-7 cells were obtained from each embryo. The most common vital aneuploidies (chromosomes X/Y, 21 were screened by fluorescence in situ hybridization (FISH. No aneuploidy was observed in 72.7% of embryos, 91% of those developed to blastocysts. Embryos were transferred on days 5-6. Clinical pregnancy was obtained in 32.8% of cases, and 60 babies were born. Patients who underwent ICSI/PGS treatment were compared with those who underwent standard ICSI treatment by examining the percentage of blastocysts, pregnancy rate, gestational length, birth height and weight. No significant differences in these parameters were observed between the groups. Day 4 biopsy procedure does not adversely affect embryo development in vitro or in vivo. The increased number of cells obtained by biopsy of morulae might facilitate diagnostic screening. There is enough time after biopsy to obtain PGD results for embryo transfer on day 5-6 in the current IVF cycle.

  7. Mitotic effects of monochromatic ultraviolet radiation at 225, 265, and 280 nm on eleven stages of the cell cycle of the grasshopper neuroblast in culture. II. Changes in progression rate and cell sequence between the stage irradiated and nuclear membrane breakdown

    International Nuclear Information System (INIS)

    Portions of embryos of the grasshopper, Chortophaga viridifasciata (DeGeer), were cultured in hanging drops under quartz cover slips. Immediately after exposure to 225, 265, or 280 nm radiation, microscope observations at 380C were begun. The morphologically identified stage and the time after treatment of selected neuroblasts were recorded at short-time intervals until prometaphase was reached. Mitotic retardation induced by irradiation of prereplication stages (metaphase, anaphase, or early telophase) or S phase (middle or late telophase, interphase, or very early prophase) is greatest in postreplication stages (early, middle, and late prophase) and absent or minimal in stages morphologically identified as parts of S phase. Ultraviolet irradiation superimposes on the normal diversity of progression rates an additional variation factor, so that cells do not necessarily reach prometaphase in the order of their sequence at the time of treatment. This suggests the need for caution in ascribing particular radiosensitivities to substages of limited duration on the basis of the order in which they attain a subsequent stage

  8. Impact of Altitude on Power Output during Cycling Stage Racing

    OpenAIRE

    Garvican-Lewis, Laura A; Clark, Bradley; Martin, David T.; Schumacher, Yorck Olaf; McDonald, Warren; Stephens, Brian; Ma, Fuhai; Kevin G Thompson; Gore, Christopher J.; Menaspà, Paolo

    2015-01-01

    Purpose The purpose of this study was to quantify the effects of moderate-high altitude on power output, cadence, speed and heart rate during a multi-day cycling tour. Methods Power output, heart rate, speed and cadence were collected from elite male road cyclists during maximal efforts of 5, 15, 30, 60, 240 and 600 s. The efforts were completed in a laboratory power-profile assessment, and spontaneously during a cycling race simulation near sea-level and an international cycling race at mode...

  9. Impact of Altitude on Power Output during Cycling Stage Racing.

    Directory of Open Access Journals (Sweden)

    Laura A Garvican-Lewis

    Full Text Available The purpose of this study was to quantify the effects of moderate-high altitude on power output, cadence, speed and heart rate during a multi-day cycling tour.Power output, heart rate, speed and cadence were collected from elite male road cyclists during maximal efforts of 5, 15, 30, 60, 240 and 600 s. The efforts were completed in a laboratory power-profile assessment, and spontaneously during a cycling race simulation near sea-level and an international cycling race at moderate-high altitude. Matched data from the laboratory power-profile and the highest maximal mean power output (MMP and corresponding speed and heart rate recorded during the cycling race simulation and cycling race at moderate-high altitude were compared using paired t-tests. Additionally, all MMP and corresponding speeds and heart rates were binned per 1000 m (3000 m according to the average altitude of each ride. Mixed linear modelling was used to compare cycling performance data from each altitude bin.Power output was similar between the laboratory power-profile and the race simulation, however MMPs for 5-600 s and 15, 60, 240 and 600 s were lower (p ≤ 0.005 during the race at altitude compared with the laboratory power-profile and race simulation, respectively. Furthermore, peak power output and all MMPs were lower (≥ 11.7%, p ≤ 0.001 while racing >3000 m compared with rides completed near sea-level. However, speed associated with MMP 60 and 240 s was greater (p < 0.001 during racing at moderate-high altitude compared with the race simulation near sea-level.A reduction in oxygen availability as altitude increases leads to attenuation of cycling power output during competition. Decrement in cycling power output at altitude does not seem to affect speed which tended to be greater at higher altitudes.

  10. Cell cycle control in Plasmodium falciparum: a genomics perspective

    OpenAIRE

    Waters, A. P.; Janse, C.J.; Doerig, Christian; Chakrabarti, Debopam

    2004-01-01

    The molecular mechanisms regulating cell proliferation and development in malaria parasites are still largely unknown. Phenomenological observations, pertaining to the organisation of the cell cycle during schizogony or to the signal transduction pathways whose activation is responsible for the developmental stage transitions, can now be complemented with information gathered from genomic databases. The PlasmoDB database has been used extensively to identify putative homologues of a number of...

  11. A Coarse Estimation of Cell Size Region from a Mesoscopic Stochastic Cell Cycle Model

    Institute of Scientific and Technical Information of China (English)

    YI Ming; JIA Ya; LIU Quan; ZHU Chun-Lian; YANG Li-Jian

    2007-01-01

    Based on a deterministic cell cycle model of fission yeast, the effects of the finite cell size on the cell cycle regulation in wee1- cdc25△ double mutant type are numerically studied by using of the chemical Langevin equations. It is found that at a certain region of cell size, our numerical results from the chemical Langevin equations are in good qualitative agreement with the experimental observations. The two resettings to the G2 phase from early stages of mitosis can be induced under the moderate cell size. The quantized cycle times can be observed during such a cell size region. Therefore, a coarse estimation of cell size is obtained from the mesoscopic stochastic cell cycle model.

  12. Vorinostat, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

    Science.gov (United States)

    2016-06-20

    Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  13. Job Satisfaction in Dual-Career Women at Three Family Life Cycle Stages.

    Science.gov (United States)

    Cron, Elyce A.

    2001-01-01

    Dual-career women (n=197) completed assessments of career attitudes, dyadic adjustment, and family adaptability and cohesion. Cohesion in the early life-cycle and adaptability in the late life-cycle were significant predictors of job satisfaction. Satisfaction increased as each life-cycle stage progressed. (Contains 25 references.) (SK)

  14. Cell cycle control after DNA damage: arrest, recovery and adaptation

    International Nuclear Information System (INIS)

    DNA damage triggers surveillance mechanisms, the DNA checkpoints, that control the genome integrity. The DNA checkpoints induce several responses, either cellular or transcriptional, that favor DNA repair. In particular, activation of the DNA checkpoints inhibits cell cycle progression in all phases, depending on the stage when lesions occur. These arrests are generally transient and cells ultimately reenter the cell division cycle whether lesions have been repaired (this process is termed 'recovery') or have proved un-repairable (this option is called 'adaptation'). The mechanisms controlling cell cycle arrests, recovery and adaptation are largely conserved among eukaryotes, and much information is now available for the yeast Saccharomyces cerevisiae, that is used as a model organism in these studies. (author)

  15. Modulation of Golgi-associated microtubule nucleation throughout the cell cycle

    Science.gov (United States)

    Maia, Ana Rita; Zhu, Xiaodong; Miller, Paul; Gu, Guoqiang; Maiato, Helder; Kaverina, Irina

    2013-01-01

    A microtubule (MT) sub-population that emanates from Golgi membrane has been recently shown to comprise a significant part of MT network in interphase cells. In this study, we address whether Golgi membrane, which is being extensively remodeled throughout the cell cycle, retains its ability to nucleate MTs at diverse cell cycle stages. Live cell imaging and immunofluorescence microscopy reveals that Golgi-derived MTs form at multiple stages of the cell cycle, including G1, G2 and distinct phases of mitosis. However, the capacity of Golgi to nucleate MTs in mitosis is strongly down-regulated as compared to interphase, indicating that this property is cell-cycle regulated. We demonstrate that Golgi-derived MTs are indispensable for efficient Golgi assembly in telophase, and speculate that these non-centrosomal MTs may hold specific functions at other cell cycle stages. PMID:23027431

  16. Does Arabidopsis thaliana DREAM of cell cycle control?

    Science.gov (United States)

    Fischer, Martin; DeCaprio, James A

    2015-08-01

    Strict temporal control of cell cycle gene expression is essential for all eukaryotes including animals and plants. DREAM complexes have been identified in worm, fly, and mammals, linking several distinct transcription factors to coordinate gene expression throughout the cell cycle. In this issue of The EMBO Journal, Kobayashi et al (2015) identify distinct activator and repressor complexes for genes expressed during the G2 and M phases in Arabidopsis that can be temporarily separated during proliferating and post‐mitotic stages of development. The complexes incorporate specific activator and repressor MYB and E2F transcription factors and indicate the possibility of the existence of multiple DREAM complexes in plants. PMID:26089020

  17. Performance evaluation of two-stage fuel cycle from SFR to PWR

    International Nuclear Information System (INIS)

    One potential fuel cycle option being considered is a two-stage fuel cycle system involving the continuous recycle of transuranics in a fast reactor and the use of bred plutonium in a thermal reactor. The first stage is a Sodium-cooled Fast Reactor (SFR) fuel cycle with metallic U-TRU-Zr fuel. The SFRs need to have a breeding ratio greater than 1.0 in order to produce fissile material for use in the second stage. The second stage is a PWR fuel cycle with uranium and plutonium mixed oxide fuel based on the design and performance of the current state-of-the-art commercial PWRs with an average discharge burnup of 50 MWd/kgHM. This paper evaluates the possibility of this fuel cycle option and discusses its fuel cycle performance characteristics. The study focuses on an equilibrium stage of the fuel cycle. Results indicate that, in order to avoid a positive coolant void reactivity feedback in the stage-2 PWR, the reactor requires high quality of plutonium from the first stage and minor actinides in the discharge fuel of the PWR needs to be separated and sent back to the stage-1 SFR. The electricity-sharing ratio between the 2 stages is 87.0% (SFR) to 13.0% (PWR) for a TRU inventory ratio (the mass of TRU in the discharge fuel divided by the mass of TRU in the fresh fuel) of 1.06. A sensitivity study indicated that by increasing the TRU inventory ratio to 1.13, The electricity generation fraction of stage-2 PWR is increased to 28.9%. The two-stage fuel cycle system considered in this study was found to provide a high uranium utilization (>80%). (authors)

  18. CT staging of renal cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To assess the usefulness of computerized tomography (CT) in the characterization of renal masses, in order to stage them, determine their prognosis and their appropriate clinical and/or surgical management. Material and Methods: Between 1988 and 2001, we selected 63 patients with renal tumors that had been examined by pathology. Patient's ages ranged from 16 to 88 years (25 women, 38 men). The studies were performed with a sequential helical CT, using 5 mm thickness sections every 5mm evaluating the cortico medullar and nephrographic phases. Renal tumors were characterized and staged without any knowledge about the pathological findings; subsequently the tomographic characteristics were compared to such findings. The following characteristics were evaluated: 1) mixed solid-cystic nature; 2) size; 3) borders; 4) enhancement; 5) necrosis; 6) hemorrhage; 7) central scar; 8) presence of fat; 9) collecting system; 10) capsular invasion; 11) perirenal fat invasion; 12) vessels; 13) Gerota's fascia; 14) lymph nodes; and 15) local and/or distant metastases. Results: Of the 63 tumors, 2 were complicated cysts; of the 61 remaining tumors, 10 were angiomyolipomas, 1 was a renal lymphoma, 1 was a focal xantogranulomatose pyelonephritis, 1 was a metanephric adenoma, 3 papillary renal cell carcinoma (RCC), 4 transitional cell tumors, 4 oncocytomas, 37 clear cell renal carcinoma. The CT could correctly characterize the 2 cystic tumors as such, as well as the 9 angiomyolipomas and the 4 transitional cell tumors. The 48 other tumors (1 angiomyolipoma, 1 lymphoma, 1 focal xantogranulomatose pyelonephritis, 1 metanephric adenoma, 3 papillary RCC, 4 oncocytomas, and 37 cell renal carcinomas) remaining were characterized as renal adenocarcinomas and CT staged. Conclusion: CT is a useful method to characterize renal masses since it determines their solid-cystic or fatty structure; aiding in many cases to define a surgical treatment. For the CT staging of renal tumors, the

  19. Cell Cycle Deregulation in Ewing's Sarcoma Pathogenesis

    Directory of Open Access Journals (Sweden)

    Ashley A. Kowalewski

    2011-01-01

    Full Text Available Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22(q24;q12. This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered.

  20. Spirocyclic chromanes exhibit antiplasmodial activities and inhibit all intraerythrocytic life cycle stages

    Science.gov (United States)

    Roberts, Bracken F.; Iyamu, Iredia D.; Lee, Sukjun; Lee, Eunyoung; Ayong, Lawrence; Kyle, Dennis E.; Yuan, Yu; Manetsch, Roman; Chakrabarti, Debopam

    2016-01-01

    We screened a collection of synthetic compounds consisting of natural-product-like substructural motifs to identify a spirocyclic chromane as a novel antiplasmodial pharmacophore using an unbiased cell-based assay. The most active spirocyclic compound UCF 201 exhibits a 50% effective concentration (EC50) of 350 nM against the chloroquine-resistant Dd2 strain and a selectivity over 50 using human liver HepG2 cells. Our analyses of physicochemical properties of UCF 201 showed that it is in compliance with Lipinski's parameters and has an acceptable physicochemical profile. We have performed a limited structure-activity-relationship study with commercially available chromanes preserving the spirocyclic motif. Our evaluation of stage specificities of UCF 201 indicated that the compound is early-acting in blocking parasite development at ring, trophozoite and schizont stages of development as well as merozoite invasion. SPC is an attractive lead candidate scaffold because of its ability to act on all stages of parasite's aexual life cycle unlike current antimalarials. PMID:27054067

  1. Spirocyclic chromanes exhibit antiplasmodial activities and inhibit all intraerythrocytic life cycle stages

    Directory of Open Access Journals (Sweden)

    Bracken F. Roberts

    2016-04-01

    Full Text Available We screened a collection of synthetic compounds consisting of natural-product-like substructural motifs to identify a spirocyclic chromane as a novel antiplasmodial pharmacophore using an unbiased cell-based assay. The most active spirocyclic compound UCF 201 exhibits a 50% effective concentration (EC50 of 350 nM against the chloroquine-resistant Dd2 strain and a selectivity over 50 using human liver HepG2 cells. Our analyses of physicochemical properties of UCF 201 showed that it is in compliance with Lipinski's parameters and has an acceptable physicochemical profile. We have performed a limited structure-activity-relationship study with commercially available chromanes preserving the spirocyclic motif. Our evaluation of stage specificities of UCF 201 indicated that the compound is early-acting in blocking parasite development at ring, trophozoite and schizont stages of development as well as merozoite invasion. SPC is an attractive lead candidate scaffold because of its ability to act on all stages of parasite's aexual life cycle unlike current antimalarials.

  2. REC46 gene of Saccharomyces cerevisiae controls mitotic chromosomal stability, recombination and sporulation: cell-type and life cycle stage specific expression of the rec46-1 mutation

    International Nuclear Information System (INIS)

    Studies of chromosomal recombination during mitosis and meiosis of Saccharomyces cerevisiae have demonstrated that recombination at these two distinct stages of the yeast life cycle proceeds by mechanisms that appear similar but involve discrete mitosis-specific and meiosis-specific properties. UV radiation induced REC mutants are being employed as a genetic tool to identify the partial reactions comprising recombination and the involvement of individual REC gene products in mitotic and meiotic recombination. The sequence of molecular events that results in genetic recombination in eukaryotes is presently ill-defined. Genetic characterization of REC gene mutants and biochemical analyses of them for discrete defects in DNA metabolic proteins and enzymes (in collaboration with the laboratory of Junko Hosoda) are beginning to remedy this gap in the authors knowledge. This report summarizes the genetic properties of the rec46-1 mutation

  3. Cell cycle phases in the unequal mother/daughter cell cycles of Saccharomyces cerevisiae.

    OpenAIRE

    Brewer, B J; Chlebowicz-Sledziewska, E; Fangman, W L

    1984-01-01

    During cell division in the yeast Saccharomyces cerevisiae mother cells produce buds (daughter cells) which are smaller and have longer cell cycles. We performed experiments to compare the lengths of cell cycle phases in mothers and daughters. As anticipated from earlier indirect observations, the longer cell cycle time of daughter cells is accounted for by a longer G1 interval. The S-phase and the G2-phase are of the same duration in mother and daughter cells. An analysis of five isogenic st...

  4. Sonic Hedgehog Opposes Epithelial Cell Cycle Arrest

    OpenAIRE

    Fan, Hongran; Khavari, Paul A

    1999-01-01

    Stratified epithelium displays an equilibrium between proliferation and cell cycle arrest, a balance that is disrupted in basal cell carcinoma (BCC). Sonic hedgehog (Shh) pathway activation appears sufficient to induce BCC, however, the way it does so is unknown. Shh-induced epidermal hyperplasia is accompanied by continued cell proliferation in normally growth arrested suprabasal cells in vivo. Shh-expressing cells fail to exit S and G2/M phases in response to calcium-induced differentiation...

  5. Fuel cell and advanced turbine power cycle

    Energy Technology Data Exchange (ETDEWEB)

    White, D.J. [Solar Turbines, Inc., San Diego, CA (United States)

    1995-10-19

    Solar Turbines, Incorporated (Solar) has a vested interest in the integration of gas turbines and high temperature fuel cells and in particular, solid oxide fuel cells (SOFCs). Solar has identified a parallel path approach to the technology developments needed for future products. The primary approach is to move away from the simple cycle industrial machines of the past and develop as a first step more efficient recuperated engines. This move was prompted by the recognition that the simple cycle machines were rapidly approaching their efficiency limits. Improving the efficiency of simple cycle machines is and will become increasingly more costly. Each efficiency increment will be progressively more costly than the previous step.

  6. Recalled, Present, and Predicted Satisfaction in Stages of the Family Life Cycle in New Zealand

    Science.gov (United States)

    Smart, Mollie S.; Smart, Russell C.

    1975-01-01

    Satisfaction in family living was studied in a New Zealand sample of 191 men and 285 women in the eight stages of the family life cycle. Results were compared with Rollins and Feldman's American sample. (Author)

  7. The cell cycle and acute kidney injury

    OpenAIRE

    Price, Peter M.; Safirstein, Robert L.; Megyesi, Judit

    2009-01-01

    Acute kidney injury (AKI) activates pathways of cell death and cell proliferation. Although seemingly discrete and unrelated mechanisms, these pathways can now be shown to be connected and even to be controlled by similar pathways. The dependence of the severity of renal-cell injury on cell cycle pathways can be used to control and perhaps to prevent acute kidney injury. This review is written to address the correlation between cellular life and death in kidney tubules, especially in acute ki...

  8. A cell cycle and nutritional checkpoint controlling bacterial surface adhesion.

    Directory of Open Access Journals (Sweden)

    Aretha Fiebig

    2014-01-01

    Full Text Available In natural environments, bacteria often adhere to surfaces where they form complex multicellular communities. Surface adherence is determined by the biochemical composition of the cell envelope. We describe a novel regulatory mechanism by which the bacterium, Caulobacter crescentus, integrates cell cycle and nutritional signals to control development of an adhesive envelope structure known as the holdfast. Specifically, we have discovered a 68-residue protein inhibitor of holdfast development (HfiA that directly targets a conserved glycolipid glycosyltransferase required for holdfast production (HfsJ. Multiple cell cycle regulators associate with the hfiA and hfsJ promoters and control their expression, temporally constraining holdfast development to the late stages of G1. HfiA further functions as part of a 'nutritional override' system that decouples holdfast development from the cell cycle in response to nutritional cues. This control mechanism can limit surface adhesion in nutritionally sub-optimal environments without affecting cell cycle progression. We conclude that post-translational regulation of cell envelope enzymes by small proteins like HfiA may provide a general means to modulate the surface properties of bacterial cells.

  9. Evaluation of Uncertainty on the Stages of Business Cycle: Implementation of Quantum Principles

    OpenAIRE

    Anna Svirina; Elena Parfenova; Elena Shurkina

    2014-01-01

    The goal of the research is to propose implementation of quantum principles for evaluation of economic development on stages of business cycle, define the difference between traditional (deterministic) and quantum approaches and to provide quantitative analysis based argumentation for use of quantum economic principles in evaluation of internal and external factors on the stages of business cycle. The object of the study is possibility and reliability of quantum economic principles implementa...

  10. Final Report on Two-Stage Fast Spectrum Fuel Cycle Options

    International Nuclear Information System (INIS)

    This report presents the performance characteristics of two ''two-stage'' fast spectrum fuel cycle options proposed to enhance uranium resource utilization and to reduce nuclear waste generation. One is a two-stage fast spectrum fuel cycle option of continuous recycle of plutonium (Pu) in a fast reactor (FR) and subsequent burning of minor actinides (MAs) in an accelerator-driven system (ADS). The first stage is a sodium-cooled FR fuel cycle starting with low-enriched uranium (LEU) fuel; at the equilibrium cycle, the FR is operated using the recovered Pu and natural uranium without supporting LEU. Pu and uranium (U) are co-extracted from the discharged fuel and recycled in the first stage, and the recovered MAs are sent to the second stage. The second stage is a sodium-cooled ADS in which MAs are burned in an inert matrix fuel form. The discharged fuel of ADS is reprocessed, and all the recovered heavy metals (HMs) are recycled into the ADS. The other is a two-stage FR/ADS fuel cycle option with MA targets loaded in the FR. The recovered MAs are not directly sent to ADS, but partially incinerated in the FR in order to reduce the amount of MAs to be sent to the ADS. This is a heterogeneous recycling option of transuranic (TRU) elements

  11. Impact of Life-Cycle Stage and Gender on the Ability to Balance Work and Family Responsibilities.

    Science.gov (United States)

    Higgins, Christopher; And Others

    1994-01-01

    Examined impact of gender and life-cycle stage on three components of work-family conflict using sample of 3,616 respondents. For men, levels of work-family conflict were moderately lower in each successive life-cycle stage. For women, levels were similar in two early life-cycle stages but were significantly lower in later life-cycle stage.…

  12. Fuel cell hybrid taxi life cycle analysis

    International Nuclear Information System (INIS)

    A small fleet of classic London Taxis (Black cabs) equipped with hydrogen fuel cell power systems is being prepared for demonstration during the 2012 London Olympics. This paper presents a Life Cycle Analysis for these vehicles in terms of energy consumption and CO2 emissions, focusing on the impacts of alternative vehicle technologies for the Taxi, combining the fuel life cycle (Tank-to-Wheel and Well-to-Tank) and vehicle materials Cradle-to-Grave. An internal combustion engine diesel taxi was used as the reference vehicle for the currently available technology. This is compared to battery and fuel cell vehicle configurations. Accordingly, the following energy pathways are compared: diesel, electricity and hydrogen (derived from natural gas steam reforming). Full Life Cycle Analysis, using the PCO-CENEX drive cycle, (derived from actual London Taxi drive cycles) shows that the fuel cell powered vehicle configurations have lower energy consumption (4.34 MJ/km) and CO2 emissions (235 g/km) than both the ICE Diesel (9.54 MJ/km and 738 g/km) and the battery electric vehicle (5.81 MJ/km and 269 g/km). - Highlights: → A Life Cycle Analysis of alternative vehicle technologies for the London Taxi was performed. → The hydrogen powered vehicles have the lowest energy consumption and CO2 emissions results. → A hydrogen powered solution can be a sustainable alternative in a full life cycle framework.

  13. A stochastic spatiotemporal model of a response-regulator network in the Caulobacter crescentus cell cycle

    Science.gov (United States)

    Li, Fei; Subramanian, Kartik; Chen, Minghan; Tyson, John J.; Cao, Yang

    2016-06-01

    The asymmetric cell division cycle in Caulobacter crescentus is controlled by an elaborate molecular mechanism governing the production, activation and spatial localization of a host of interacting proteins. In previous work, we proposed a deterministic mathematical model for the spatiotemporal dynamics of six major regulatory proteins. In this paper, we study a stochastic version of the model, which takes into account molecular fluctuations of these regulatory proteins in space and time during early stages of the cell cycle of wild-type Caulobacter cells. We test the stochastic model with regard to experimental observations of increased variability of cycle time in cells depleted of the divJ gene product. The deterministic model predicts that overexpression of the divK gene blocks cell cycle progression in the stalked stage; however, stochastic simulations suggest that a small fraction of the mutants cells do complete the cell cycle normally.

  14. Improved Gene Targeting through Cell Cycle Synchronization.

    Directory of Open Access Journals (Sweden)

    Vasiliki Tsakraklides

    Full Text Available Gene targeting is a challenge in organisms where non-homologous end-joining is the predominant form of recombination. We show that cell division cycle synchronization can be applied to significantly increase the rate of homologous recombination during transformation. Using hydroxyurea-mediated cell cycle arrest, we obtained improved gene targeting rates in Yarrowia lipolytica, Arxula adeninivorans, Saccharomyces cerevisiae, Kluyveromyces lactis and Pichia pastoris demonstrating the broad applicability of the method. Hydroxyurea treatment enriches for S-phase cells that are active in homologous recombination and enables previously unattainable genomic modifications.

  15. Flavonoids: from cell cycle regulation to biotechnology.

    Science.gov (United States)

    Woo, Ho-Hyung; Jeong, Byeong Ryong; Hawes, Martha C

    2005-03-01

    Flavonoids have been proposed to play diverse roles in plant growth and development, including defense, symbiosis, pollen development and male fertility, polar auxin transport, and protection against ultraviolet radiation. Recently, a new role in cell cycle regulation has emerged. Genetic alteration of glucuronide metabolism by altered expression of a Pisum sativum UDP-glucuronosyltransferase (PsUGT1) results in an altered cell cycle in pea, alfalfa, and Arabidopsis. In alfalfa, altered expression of PsUGT1 results in accumulation of a flavonoid-like compound that suppresses growth of cultured cells. The results are consistent with the hypothesis that PsUGT1 functions by controlling cellular levels of a factor controlling cell cycle (FCC). PMID:15834800

  16. Identification of Paralogous Life-Cycle Stage Specific Cytoskeletal Proteins in the Parasite Trypanosoma brucei

    OpenAIRE

    Neil Portman; Keith Gull

    2014-01-01

    The life cycle of the African trypanosome Trypanosoma brucei, is characterised by a transition between insect and mammalian hosts representing very different environments that present the parasite with very different challenges. These challenges are met by the expression of life-cycle stage-specific cohorts of proteins, which function in systems such as metabolism and immune evasion. These life-cycle transitions are also accompanied by morphological rearrangements orchestrated by microtubule ...

  17. Life-cycle stages, mobility, and metropolitan change: 1. Theoretcal issues

    OpenAIRE

    M J Webber

    1983-01-01

    It is shown how one dynamic element may be incorporated into operational urban models. That element is household mobility, caused by the evolution of households through stages in the life cycle. First, the significance of life-cycle changes as an agent causing intraurban mobility is reviewed; next, a matrix representation of the dynamics of life-cycle changes is examined; and then the properties of that representation are described.

  18. Final Report on Two-Stage Fast Spectrum Fuel Cycle Options

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Won Sik [Purdue Univ., West Lafayette, IN (United States); Lin, C. S. [Purdue Univ., West Lafayette, IN (United States); Hader, J. S. [Purdue Univ., West Lafayette, IN (United States); Park, T. K. [Purdue Univ., West Lafayette, IN (United States); Deng, P. [Purdue Univ., West Lafayette, IN (United States); Yang, G. [Purdue Univ., West Lafayette, IN (United States); Jung, Y. S. [Purdue Univ., West Lafayette, IN (United States); Kim, T. K. [Argonne National Lab. (ANL), Argonne, IL (United States); Stauff, N. E. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2016-01-30

    This report presents the performance characteristics of two “two-stage” fast spectrum fuel cycle options proposed to enhance uranium resource utilization and to reduce nuclear waste generation. One is a two-stage fast spectrum fuel cycle option of continuous recycle of plutonium (Pu) in a fast reactor (FR) and subsequent burning of minor actinides (MAs) in an accelerator-driven system (ADS). The first stage is a sodium-cooled FR fuel cycle starting with low-enriched uranium (LEU) fuel; at the equilibrium cycle, the FR is operated using the recovered Pu and natural uranium without supporting LEU. Pu and uranium (U) are co-extracted from the discharged fuel and recycled in the first stage, and the recovered MAs are sent to the second stage. The second stage is a sodium-cooled ADS in which MAs are burned in an inert matrix fuel form. The discharged fuel of ADS is reprocessed, and all the recovered heavy metals (HMs) are recycled into the ADS. The other is a two-stage FR/ADS fuel cycle option with MA targets loaded in the FR. The recovered MAs are not directly sent to ADS, but partially incinerated in the FR in order to reduce the amount of MAs to be sent to the ADS. This is a heterogeneous recycling option of transuranic (TRU) elements

  19. Signatures of natural selection between life cycle stages separated by metamorphosis in European eel

    DEFF Research Database (Denmark)

    Pujolar, J.M.; Jacobsen, M.W.; Bekkevold, Dorte;

    2015-01-01

    Species showing complex life cycles provide excellent opportunities to study the genetic associations between life cycle stages, as selective pressures may differ before and after metamorphosis. The European eel presents a complex life cycle with two metamorphoses, a first metamorphosis from larvae...... into glass eels (juvenile stage) and a second metamorphosis into silver eels (adult stage). We tested the hypothesis that different genes and gene pathways will be under selection at different life stages when comparing the genetic associations between glass eels and silver eels. Results: We used two...... sets of markers to test for selection: first, we genotyped individuals using a panel of 80 coding-gene single nucleotide polymorphisms (SNPs) developed in American eel; second, we investigated selection at the genome level using a total of 153,423 RAD-sequencing generated SNPs widely distributed across...

  20. Germs within Worms: Localization of Neorickettsia sp. within Life Cycle Stages of the Digenean Plagiorchis elegans.

    Science.gov (United States)

    Greiman, Stephen E; Rikihisa, Yasuko; Cain, Jacob; Vaughan, Jefferson A; Tkach, Vasyl V

    2016-04-15

    Neorickettsiaspp. are bacterial endosymbionts of parasitic flukes (Digenea) that also have the potential to infect and cause disease (e.g., Sennetsu fever) in the vertebrate hosts of the fluke. One of the largest gaps in our knowledge ofNeorickettsiabiology is the very limited information available regarding the localization of the bacterial endosymbiont within its digenean host. In this study, we used indirect immunofluorescence microscopy to visualizeNeorickettsiasp. within several life cycle stages of the digeneanPlagiorchis elegans Individual sporocysts, cercariae, metacercariae, and adults ofP. elegansnaturally infected withNeorickettsiasp. were obtained from our laboratory-maintained life cycle, embedded, sectioned, and prepared for indirect immunofluorescence microscopy using anti-Neorickettsiaristiciihorse serum as the primary antibody.Neorickettsiasp. was found within the tegument of sporocysts, throughout cercarial embryos (germ balls) and fully formed cercariae (within the sporocysts), throughout metacercariae, and within the tegument, parenchyma, vitellaria, uteri, testes, cirrus sacs, and eggs of adults. Interestingly,Neorickettsiasp. was not found within the ovarian tissue. This suggests that vertical transmission ofNeorickettsiawithin adult digeneans occurs via the incorporation of infected vitelline cells into the egg rather than direct infection of the ooplasm of the oocyte, as has been described for other bacterial endosymbionts of invertebrates (e.g.,RickettsiaandWolbachia). PMID:26873314

  1. Identification of Proteins Whose Synthesis Is Modulated During the Cell Cycle of Saccharomyces cerevisiae

    OpenAIRE

    Lörincz, Attila T.; Miller, Mark J.; Xuong, Nguyen-Huu; Geiduschek, E. Peter

    1982-01-01

    We examined the synthesis and turnover of individual proteins in the Saccharomyces cerevisiae cell cycle. Proteins were pulse-labeled with radioactive isotope (35S or 14C) in cells at discrete cycle stages and then resolved on two-dimensional gels and analyzed by a semiautomatic procedure for quantitating gel electropherogram-autoradiographs. The cells were obtained by one of three methods: (i) isolation of synchronous subpopulations of growing cells by zonal centrifugation; (ii) fractionatio...

  2. Performance prediction and parametric analysis of two stage stirling cycle cryocooler

    Science.gov (United States)

    Natu, P. V.; Narayankhedkar, K. G.

    The lowest temperature that can be achieved inStirling cycle cryocooler is governed by various losses. This paper presents performance prediction of Two Stage Stirling Cryocooler(for 20K as the second stage temperature) by using second order analysis which calculates the ideal refrigerating effect at intermediate and final stage temperatures and the ideal power input. The losses are found out for both the stages to determine the actual refrigerating effects and power input. The results obtained are in good agreement with reported values. The performance of the cryocooler is governed by various operating and geometric parameters. Parametric analysis is carried.

  3. Effect of simulated stages of the canine oestrous cycle on Escherichia coli binding to canine endometrium.

    Science.gov (United States)

    Krekeler, N; Lodge, K M; Anderson, G A; Browning, G F; Charles, J A; Wright, P J

    2012-12-01

    Pyometra, a prevalent infectious uterine disease that affects intact middle-aged bitches, is typically associated with Escherichia coli. Our hypotheses were (i) that bacterial adhesion to canine endometrium differs between different stages of the oestrous cycle and (ii) that the adhesin FimH facilitates this adhesion. Twelve post-pubertal, ovariectomized greyhound bitches were treated with exogenous hormones to simulate different stages of the oestrous cycle. Tissue samples from each uterus were incubated with a pathogenic E. coli strain carrying the fimH gene, but no other adhesin genes (P4-wt)--or an E. coli strain in which fimH was insertionally inactivated (P4-∆fimH::kan)--or with phosphate-buffered saline as a negative control. After washing, tissue samples were homogenized for quantification of adherent bacteria. The differences in binding to canine endometrium at different stages of the oestrous cycle were not significant. However, the mean difference in binding of the P4-wt and the P4-∆fimH::kan across all stages of the simulated oestrous cycle was significant (p < 0.001 by paired t-test on geometric means). Individual differences in numbers of P4-wt bacteria bound between dogs might suggest genetic variations or epigenetic differences in FimH receptor expression by the endometrium, unrelated to the stage of the oestrous cycle. PMID:23279531

  4. Identification of paralogous life-cycle stage specific cytoskeletal proteins in the parasite Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Neil Portman

    Full Text Available The life cycle of the African trypanosome Trypanosoma brucei, is characterised by a transition between insect and mammalian hosts representing very different environments that present the parasite with very different challenges. These challenges are met by the expression of life-cycle stage-specific cohorts of proteins, which function in systems such as metabolism and immune evasion. These life-cycle transitions are also accompanied by morphological rearrangements orchestrated by microtubule dynamics and associated proteins of the subpellicular microtubule array. Here we employed a gel-based comparative proteomic technique, Difference Gel Electrophoresis, to identify cytoskeletal proteins that are expressed differentially in mammalian infective and insect form trypanosomes. From this analysis we identified a pair of novel, paralogous proteins, one of which is expressed in the procyclic form and the other in the bloodstream form. We show that these proteins, CAP51 and CAP51V, localise to the subpellicular corset of microtubules and are essential for correct organisation of the cytoskeleton and successful cytokinesis in their respective life cycle stages. We demonstrate for the first time redundancy of function between life-cycle stage specific paralogous sets in the cytoskeleton and reveal modification of cytoskeletal components in situ prior to their removal during differentiation from the bloodstream form to the insect form. These specific results emphasise a more generic concept that the trypanosome genome encodes a cohort of cytoskeletal components that are present in at least two forms with life-cycle stage-specific expression.

  5. Control points within the cell cycle

    International Nuclear Information System (INIS)

    Evidence of the temporal order of chromosomal DNA replication argues favorably for the view that the cell cycle is controlled by genes acting in sequence whose time of expression is determined by mitosis and the amount of nuclear DNA (2C vs 4C) in the cell. Gl and G2 appear to be carbohydrate dependent in that cells starved of either carbohydrate of phosphate fail to make these transitions. Cells deprived of nitrate, however, fail only at Gl to S transition indicating that the controls that operate in G1 differ from those that operate in G2. 46 references, 5 figures

  6. Control points within the cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Van' t Hof, J.

    1984-01-01

    Evidence of the temporal order of chromosomal DNA replication argues favorably for the view that the cell cycle is controlled by genes acting in sequence whose time of expression is determined by mitosis and the amount of nuclear DNA (2C vs 4C) in the cell. Gl and G2 appear to be carbohydrate dependent in that cells starved of either carbohydrate of phosphate fail to make these transitions. Cells deprived of nitrate, however, fail only at Gl to S transition indicating that the controls that operate in G1 differ from those that operate in G2. 46 references, 5 figures.

  7. Mitochondrial dynamics and the cell cycle

    Science.gov (United States)

    Nuclear-mitochondrial (NM) communication impacts many aspects of plant development including vigor, sterility and viability. Dynamic changes in mitochondrial number, shape, size, and cellular location takes place during the cell cycle possibly impacting the process itself and leading to distribution...

  8. Cell Cycle Progression of Human Cells Cultured in Rotating Bioreactor

    Science.gov (United States)

    Parks, Kelsey

    2009-01-01

    Space flight has been shown to alter the astronauts immune systems. Because immune performance is complex and reflects the influence of multiple organ systems within the host, scientists sought to understand the potential impact of microgravity alone on the cellular mechanisms critical to immunity. Lymphocytes and their differentiated immature form, lymphoblasts, play an important and integral role in the body's defense system. T cells, one of the three major types of lymphocytes, play a central role in cell-mediated immunity. They can be distinguished from other lymphocyte types, such as B cells and natural killer cells by the presence of a special receptor on their cell surface called T cell receptors. Reported studies have shown that spaceflight can affect the expression of cell surface markers. Cell surface markers play an important role in the ability of cells to interact and to pass signals between different cells of the same phenotype and cells of different phenotypes. Recent evidence suggests that cell-cycle regulators are essential for T-cell function. To trigger an effective immune response, lymphocytes must proliferate. The objective of this project is to investigate the changes in growth of human cells cultured in rotating bioreactors and to measure the growth rate and the cell cycle distribution for different human cell types. Human lymphocytes and lymphoblasts will be cultured in a bioreactor to simulate aspects of microgravity. The bioreactor is a cylindrical culture vessel that incorporates the aspects of clinostatic rotation of a solid fluid body around a horizontal axis at a constant speed, and compensates gravity by rotation and places cells within the fluid body into a sustained free-fall. Cell cycle progression and cell proliferation of the lymphocytes will be measured for a number of days. In addition, RNA from the cells will be isolated for expression of genes related in cell cycle regulations.

  9. PERIODIZATION LIFE CYCLE STAGE OF AIRPORT DEVELOPMENT UKRAINE UNDER SPECIFICS OF THEIR BEHAVIOR

    Directory of Open Access Journals (Sweden)

    О.М. ЛОЖАЧЕВСЬКА

    2011-12-01

    Full Text Available  In the article the considered problem of division into periods of phases of life cycle of air-ports, in accordance with the features of influence of marketing environment on their activity. Authors offersown vision of problem of phase development of air-ports is offered, in accordance with conception of life cycle of organization. This approach enables to show out Ukrainian air-ports on the new stage of the strategic planning and management.

  10. Staged Combustion Cycle Rocket Engine Design Trade-Offs for Future Advanced Passenger Transport

    OpenAIRE

    Sippel, Martin; Yamashiro, Ryoma

    2012-01-01

    Staged combustion cycle rocket engines with a moderate nominal 16 MPa chamber pressure have been selected as the baseline propulsion system for the visionary intercontinental passenger transport SpaceLiner. Several technical engine design trade-offs are run by numerical simulations and results are pre-sented including: • Fuel rich vs. Full-flow cycle • Useful operational domain in MR • Regenerative cooling options of thrust chamber The engine operational domain is evaluated on ...

  11. FUEL CELL/MICRO-TURBINE COMBINED CYCLE

    Energy Technology Data Exchange (ETDEWEB)

    Larry J. Chaney; Mike R. Tharp; Tom W. Wolf; Tim A. Fuller; Joe J. Hartvigson

    1999-12-01

    A wide variety of conceptual design studies have been conducted that describe ultra-high efficiency fossil power plant cycles. The most promising of these ultra-high efficiency cycles incorporate high temperature fuel cells with a gas turbine. Combining fuel cells with a gas turbine increases overall cycle efficiency while reducing per kilowatt emissions. This study has demonstrated that the unique approach taken to combining a fuel cell and gas turbine has both technical and economic merit. The approach used in this study eliminates most of the gas turbine integration problems associated with hybrid fuel cell turbine systems. By using a micro-turbine, and a non-pressurized fuel cell the total system size (kW) and complexity has been reduced substantially from those presented in other studies, while maintaining over 70% efficiency. The reduced system size can be particularly attractive in the deregulated electrical generation/distribution environment where the market may not demand multi-megawatt central stations systems. The small size also opens up the niche markets to this high efficiency, low emission electrical generation option.

  12. Treatment Options By Stage (Ovarian Germ Cell Tumors)

    Science.gov (United States)

    ... c) cancer cells are found in the pelvic peritoneum. In stage I , cancer is found in one ... in the abdomen ) or in washings of the peritoneum ( tissue lining the peritoneal cavity). Stage II Enlarge ...

  13. The Organizational Life Cycle Stages and Effectiveness : A Study of Swedish Gazelle Companies

    OpenAIRE

    Choi, Ga Eun; Nordström, Christoffer; Llorach, Carlos

    2012-01-01

    The purpose of this thesis is to investigate the life cycle stages of the chosen gazelles in Sweden and identify their effectiveness related to the stages. Furthermore, we study whether the given characteristic of the gazelle companies correspond to the suggested characteristics of the given theoretical framework. Gazelles, as the outstanding performers of both financial profits and job creators of our society, they are always struggling to sustain growth and satisfy market needs in order to ...

  14. Life-cycle analysis of product integrated polymer solar cells

    DEFF Research Database (Denmark)

    Espinosa Martinez, Nieves; García-Valverde, Rafael; Krebs, Frederik C

    2011-01-01

    , switch and a white light emitting semiconductor diode. The polymer solar cell employed in this prototype presents a power conversion efficiency in the range of 2 to 3% yielding energy payback times (EPBT) in the range of 1.3–2 years. Based on this it is worthwhile to undertake a life-cycle study......A life cycle analysis (LCA) on a product integrated polymer solar module is carried out in this study. These assessments are well-known to be useful in developmental stages of a product in order to identify the bottlenecks for the up-scaling in its production phase for several aspects spanning from...... economics through design to functionality. An LCA study was performed to quantify the energy use and greenhouse gas (GHG) emissions from electricity use in the manufacture of a light-weight lamp based on a plastic foil, a lithium-polymer battery, a polymer solar cell, printed circuitry, blocking diode...

  15. Does Arabidopsis thaliana DREAM of cell cycle control?

    Science.gov (United States)

    Fischer, Martin; DeCaprio, James A

    2015-01-01

    Strict temporal control of cell cycle gene expression is essential for all eukaryotes including animals and plants. DREAM complexes have been identified in worm, fly, and mammals, linking several distinct transcription factors to coordinate gene expression throughout the cell cycle. In this issue of The EMBO Journal, Kobayashi et al (2015) identify distinct activator and repressor complexes for genes expressed during the G2 and M phases in Arabidopsis that can be temporarily separated during proliferating and post-mitotic stages of development. The complexes incorporate specific activator and repressor MYB and E2F transcription factors and indicate the possibility of the existence of multiple DREAM complexes in plants. PMID:26089020

  16. Vaginal Cytology of the Laboratory Rat and Mouse: Review and Criteria for the Staging of the Estrous Cycle Using Stained Vaginal Smears.

    Science.gov (United States)

    Cora, Michelle C; Kooistra, Linda; Travlos, Greg

    2015-08-01

    Microscopic evaluation of the types of cells present in vaginal smears has long been used to document the stages of the estrous cycle in laboratory rats and mice and as an index of the functional status of the hypothalamic-pituitary-ovarian axis. The estrous cycle is generally divided into the four stages of proestrus, estrus, metestrus, and diestrus. On cytological evaluation, these stages are defined by the absence, presence, or proportion of 4 basic cell types as well as by the cell density and arrangement of the cells on the slide. Multiple references regarding the cytology of the rat and mouse estrous cycle are available. Many contemporary references and studies, however, have relatively abbreviated definitions of the stages, are in reference to direct wet mount preparations, or lack comprehensive illustrations. This has led to ambiguity and, in some cases, a loss of appreciation for the encountered nuances of dividing a steadily moving cycle into 4 stages. The aim of this review is to provide a detailed description, discussion, and illustration of vaginal cytology of the rat and mouse estrous cycle as it appears on smears stained with metachromatic stains. PMID:25739587

  17. Cell cycle delays in synchronized cell populations following irradiation with heavy ions

    International Nuclear Information System (INIS)

    Mammalian cells subjected to irradiation with heavy ions were investigated for cell cycle delays. The ions used for this purpose included Ne ions in the LET range of 400 keV/μm just as well as uranium ions of 16225 keV/μm. The qualitative changes in cell cycle progression seen after irradiation with Ne ions (400 keV/μm) were similar to those observed in connection with X-rays. Following irradiation with extremely heavy ions (lead, uranium) the majority of cells were even at 45 hours still found to be in the S phase or G2M phase of the first cycle. The delay cross section 'σ-delay' was introduced as a quantity that would permit quantitative comparisons to be carried out between the changes in cell progression and other effects of radiation. In order to evaluate the influence of the number of hits on the radiation effect observed, the size of the cell nucleus was precisely determined with reference to the cycle phase and local cell density. A model to simulate those delay effects was designed in such a way that account is taken of this probability of hit and that the results can be extrapolated from the delay effects after X-irradiation. On the basis of the various probabilities of hit for cells at different cycle stages a model was developed to ascertain the intensified effect following fractionated irradiation with heavy ions. (orig./MG)

  18. RL-10 Based Combined Cycle For A Small Reusable Single-Stage-To-Orbit Launcher

    Science.gov (United States)

    Balepin, Vladimir; Price, John; Filipenco, Victor

    1999-01-01

    This paper discusses a new application of the combined propulsion known as the KLIN(TM) cycle, consisting of a thermally integrated deeply cooled turbojet (DCTJ) and liquid rocket engine (LRE). If based on the RL10 rocket engine family, the KLIN (TM) cycle makes a small single-stage-to-orbit (SSTO) reusable launcher feasible and economically very attractive. Considered in this paper are the concept and parameters of a small SSTO reusable launch vehicle (RLV) powered by the KLIN (TM) cycle (sSSTO(TM)) launcher. Also discussed are the benefits of the small launcher, the reusability, and the combined cycle application. This paper shows the significant reduction of the gross take off weight (GTOW) and dry weight of the KLIN(TM) cycle-powered launcher compared to an all-rocket launcher.

  19. Evaluation of Uncertainty on the Stages of Business Cycle: Implementation of Quantum Principles

    Directory of Open Access Journals (Sweden)

    Anna Svirina

    2014-08-01

    Full Text Available The goal of the research is to propose implementation of quantum principles for evaluation of economic development on stages of business cycle, define the difference between traditional (deterministic and quantum approaches and to provide quantitative analysis based argumentation for use of quantum economic principles in evaluation of internal and external factors on the stages of business cycle. The object of the study is possibility and reliability of quantum economic principles implementation to evaluate economic system performance. The authors analyze existing approaches towards implementation of deterministic, probabilistic and quantum models for estimating internal and external factors on stages of business cycle, define the benchmark for shift from traditional economy models and principles to quantum principles, describe the stages of business cycle from the quantum economics point of view and provide quantitative analysis of deterministic and quantum models quality on the level of enterprise to prove efficiency and reliability of quantum principles based approach. Calculations and data processing were carried out using Microsoft Excel and SSPS Statistics software.

  20. Evaluating Managerial Styles for System Development Life Cycle Stages to Ensure Software Project Success

    Science.gov (United States)

    Kocherla, Showry

    2012-01-01

    Information technology (IT) projects are considered successful if they are completed on time, within budget, and within scope. Even though, the required tools and methodologies are in place, IT projects continue to fail at a higher rate. Current literature lacks explanation for success within the stages of system development life-cycle (SDLC) such…

  1. Satisfaction in Stages of the Life Cycle, Levels of General Happiness and Frequency of Peak Experience

    Science.gov (United States)

    Stewart, Robert A. C.

    1976-01-01

    This study focuses on reported (a) satisfaction in stages of the life cycle; (b) levels of general happiness; and (c) frequency of peak experiences. Subjects were 48 undergraduate students (17 males, 31 females) at Laurentian University, Canada. Results from all three areas in this study accord closely with other relevant published work. (Author)

  2. Influence of Life Cycle Stage on Family Social Climate and Attitudes Toward the Residential Environment.

    Science.gov (United States)

    Inman, Marjorie

    The existing physical forms of housing are not always compatible with prevalent social patterns. To investigate the relationship between family system characteristics and attitudes about residential space, 64 Indiana families in 4 stages of the family life cycle (early years with no children, crowded years with at least one preschool child, peak…

  3. Heat balance analysis of single stage Gifford-McMahon cycle cryorefrigerator

    Science.gov (United States)

    Thirumaleshwar, M.; Subramanyam, S. V.

    A heat balance analysis of single stage Gifford-McMahon cycle cryorefrigerator is presented. Ideal refrigeration, actual refrigeration, net refrigeration and the various losses are tabulated. It is observed that pressure-volume losses account for a major fraction of the total losses.

  4. The cell cycle as a brake for β-cell regeneration from embryonic stem cells

    OpenAIRE

    El-Badawy, Ahmed; El-Badri, Nagwa

    2016-01-01

    The generation of insulin-producing β cells from stem cells in vitro provides a promising source of cells for cell transplantation therapy in diabetes. However, insulin-producing cells generated from human stem cells show deficiency in many functional characteristics compared with pancreatic β cells. Recent reports have shown molecular ties between the cell cycle and the differentiation mechanism of embryonic stem (ES) cells, assuming that cell fate decisions are controlled by the cell cycle ...

  5. System-level design of bacterial cell cycle control

    OpenAIRE

    McAdams, Harley H.; Shapiro, Lucy

    2009-01-01

    Understanding of the cell cycle control logic in Caulobacter has progressed to the point where we now have an integrated view of the operation of an entire bacterial cell cycle system functioning as a state machine. Oscillating levels of a few temporally-controlled master regulator proteins in a cyclical circuit drive cell cycle progression. To a striking degree, the cell cycle regulation is a whole cell phenomenon. Phospho-signaling proteins and proteases dynamically deployed to specific loc...

  6. GATA-3 regulates hematopoietic stem cell maintenance and cell-cycle entry

    OpenAIRE

    Ku, Chia-Jui; Hosoya, Tomonori; Maillard, Ivan; Engel, James Douglas

    2012-01-01

    Maintaining hematopoietic stem cell (HSC) quiescence is a critical property for the life-long generation of blood cells. Approximately 75% of cells in a highly enriched long-term repopulating HSC (LT-HSC) pool (Lin−Sca1+c-KithiCD150+CD48−) are quiescent, with only a small percentage of the LT-HSCs in cycle. Transcription factor GATA-3 is known to be vital for the development of T cells at multiple stages in the thymus and for Th2 differentiation in the peripheral organs. Although it is well d...

  7. Changes of the cell cycle regulators and cell cycle arrest in cervical cancer cells after cisplatin therapy

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To investigate the changes of the cell cycle regulators ATM,Chk2 and p53 and cell cycle arrest in HeLa cells after cisplatin therapy. Methods The proliferation-inhibiting rates of HeLa cells induced by cisplatin of different concentrations were measured by MTT assays. The mRNA and protein expressions of ATM,Chk2 and p53 of HeLa cells with and without cisplatin were detected by RT-PCR and Western blot,respectively. The cell cycle analysis was conducted by flow cytometric analysis. Results Cisplatin...

  8. Risk analysis of the aqueous fast reactor fuel cycle facility in the conceptual design stage

    International Nuclear Information System (INIS)

    This paper describes the radioactive release risk of the advanced aqueous reprocessing and fabrication facility for the fast reactor fuel cycle. Because this advanced facility is still in the conceptual design stage, the risk analysis aims at grasping the entire risk comprehensively as simple as possible. As a potential hazard, it was shown that the main process in the reprocessing and fuel fabrication facilities involved only an order of 10-3 of radioactivity in the single reactor core of large scale. Abnormal phenomena related to radioactive solution that can cause radioactive release from the facility to the environmental atmosphere in a large quantity were identified as follows: in-vessel boiling caused by loss of cooling system, a leak and fire of inflammable organic solvent in a cell, in-vessel boiling due to criticality accident, an explosion. Simplified estimation about the quantitative risk of radioactive release showed that in-vessel boiling due to loss of cooling system had the largest contribution to the non-volatile radioactive substance release in a large quantity and that criticality accidents initiated from incomplete extraction stripping of Pu nuclides were dominant in the release risk of radioactive iodine and noble gas with a short-half-life. (author)

  9. Fucci2a: A bicistronic cell cycle reporter that allows Cre mediated tissue specific expression in mice

    OpenAIRE

    Mort, Richard Lester; Ford, Matthew Jonathan; Sakaue-Sawano, Asako; Lindstrom, Nils Olof; Casadio, Angela; Douglas, Adam Thomas; Keighren, Margaret Anne; Hohenstein, Peter; Miyawaki, Atsushi; Jackson, Ian James

    2014-01-01

    Markers of cell cycle stage allow estimation of cell cycle dynamics in cell culture and during embryonic development. The Fucci system incorporates genetically encoded probes that highlight G1 and S/G2/M phases of the cell cycle allowing live imaging. However the available mouse models that incorporate Fucci are beset by problems with transgene inactivation, varying expression level, lack of conditional potential and/or the need to maintain separate transgenes—there is no transgenic mouse mod...

  10. Centrioles in the cell cycle. I. Epithelial cells

    OpenAIRE

    1982-01-01

    A study was made of the structure of the centrosome in the cell cycle in a nonsynchronous culture of pig kidney embryo (PE) cells. In the spindle pole of the metaphase cell there are two mutually perpendicular centrioles (mother and daughter) which differ in their ultrastructure. An electron-dense halo, which surrounds only the mother centriole and is the site where spindle microtubules converge, disappears at the end of telophase. In metaphase and anaphase, the mother centriole is situated p...

  11. Acanthamoeba induces cell-cycle arrest in host cells

    OpenAIRE

    Sissons, J.; Alsam, S.; Jayasekera, S.; Kim, K S; Stins, M; Khan, Naveed Ahmed

    2004-01-01

    Acanthamoeba can cause fatal granulomatous amoebic encephalitis (GAE) and eye keratitis. However, the pathogenesis and pathophysiology of these emerging diseases remain unclear. In this study, the effects of Acanthamoeba on the host cell cycle using human brain microvascular endothelial cells (HBMEC) and human corneal epithelial cells (HCEC) were determined. Two isolates of Acanthamoeba belonging to the T1 genotype (GAE isolate) and T4 genotype (keratitis isolate) were used, which showed seve...

  12. Molten-Phase Hydrolysis Stage Analysis and Experiments for the Calcium Bromine Thermochemical Cycle

    International Nuclear Information System (INIS)

    The goal of the United States Department of Energy Nuclear Hydrogen Initiative as linked with the Generation IV Nuclear Energy Systems Initiative for Gas Reactor Deployment is to develop a cost-effective, proliferation-resistant, low-greenhouse-gas emissions, and sustainable, nuclear-based energy supply system. The calcium-bromine cycle under development at Argonne National Laboratory combines both experimental and modeling studies of a novel continuous 'hybrid' cycle for hydrogen production, where 'hybrid' means that both nuclear heat and electricity are employed. Engineering the calcium-bromine cycle for continuous operation should facilitate its practical development since there will be an inherent advantage to using components and materials which will operate in a constant, non-cycling chemical and thermal environment. This paper focuses on the first and important calcium bromide hydrolysis stage to generate hydrogen bromide, which when split by electrolysis, produces hydrogen. (authors)

  13. Complex scheme of company image management on the stages of its life cycle

    Directory of Open Access Journals (Sweden)

    A.V. Kolodka

    2014-03-01

    Full Text Available The aim of the article. The aim of the article is to create a common integrated circuit image management during a life-cycle of enterprise based on internal and external economic conditions. The results of the analysis. In the article the general scheme of image management during a life-cycle of enterprise based on internal and external economic conditions is formed. There is no single view on the question of forming general concepts and approaches to image building. That threatens making the correct management actions in developing and strengthening the image by top professionals. In the article several tasks were accomplished for achieving the main goal. The basic concepts of formation and management of the company image are analyzed. According to this the main tasks of image policy on company life-cycle, the activities on the formation of internal and external image were defined. The approaches of the formation and company image management are analyzed. The features and the necessity of using different approaches to image management at each stage of the company life cycle are highlighted. Research results of modern approaches to the company image formation serve the goals of reconstruction a coherent picture of this management problem were developed. The author proved that measures for formation and management of company image should be based on the analysis of existing conditions of its image and stages of its life cycle, which will increase the efficiency of management. Conclusions and directions of further researches. Completed the system analysis of the concepts and approaches to the formation and the company image management, revealed their strengths and weaknesses. The conceptual scheme of the purposeful control of company image on the stages of its life cycle was developed. Recommendations how to use the approaches to manage company image on its life-cycle were proposed.The results obtained allow forming the image policy, which is

  14. High efficiency carbonate fuel cell/turbine hybrid power cycles

    Energy Technology Data Exchange (ETDEWEB)

    Steinfeld, G. [Energy Research Corp., Danbury, CT (United States)

    1995-10-19

    Carbonate fuel cells developed by Energy Research Corporation, in commercial 2.85 MW size, have an efficiency of 57.9 percent. Studies of higher efficiency hybrid power cycles were conducted in cooperation with METC to identify an economically competitive system with an efficiency in excess of 65 percent. A hybrid power cycle was identified that includes a direct carbonate fuel cell, a gas turbine and a steam cycle, which generates power at a LHV efficiency in excess of 70 percent. This new system is called a Tandem Technology Cycle (TTC). In a TTC operating on natural gas fuel, 95 percent of the fuel is mixed with recycled fuel cell anode exhaust, providing water for the reforming of the fuel, and flows to a direct carbonate fuel cell system which generates 72 percent of the power. The portion of the fuel cell anode exhaust which is not recycled, is burned and heat is transferred to the compressed air from a gas turbine, raising its temperature to 1800{degrees}F. The stream is then heated to 2000{degrees}F in the gas turbine burner and expands through the turbine generating 13 percent of the power. Half the exhaust from the gas turbine flows to the anode exhaust burner, and the remainder flows to the fuel cell cathodes providing the O{sub 2} and CO{sub 2} needed in the electrochemical reaction. Exhaust from the fuel cells flows to a steam system which includes a heat recovery steam generator and stages steam turbine which generates 15 percent of the TTC system power. Studies of the TTC for 200-MW and 20-MW size plants quantified performance, emissions and cost-of-electricity, and compared the characteristics of the TTC to gas turbine combined cycles. A 200-MW TTC plant has an efficiency of 72.6 percent, and is relatively insensitive to ambient temperature, but requires a heat exchanger capable of 2000{degrees}F. The estimated cost of electricity is 45.8 mills/kWhr which is not competitive with a combined cycle in installations where fuel cost is under $5.8/MMBtu.

  15. Does thermal variability experienced at the egg stage influence life history traits across life cycle stages in a small invertebrate?

    Directory of Open Access Journals (Sweden)

    Kun Xing

    Full Text Available Although effects of thermal stability on eggs have often been considered in vertebrates, there is little data thermal stability in insect eggs even though these eggs are often exposed in nature to widely fluctuating ambient conditions. The modularity of development in invertebrates might lead to compensation across life cycle stages but this remains to be tested particularly within the context of realistic temperature fluctuations encountered in nature. We simulated natural temperate fluctuations on eggs of the worldwide cruciferous insect pest, the diamondback moth (DBM, Plutella xylostella (L., while maintaining the same mean temperature (25°C±0°C, 25±4°C, 25±6°C, 25±8°C, 25±10°C, 25±12°C and assessed egg development, survival and life history traits across developmental stages. Moderate fluctuations (25±4°C, 25±6°C did not influence performance compared to the constant temperature treatment, and none of the treatments influenced egg survival. However the wide fluctuating temperatures (25±10°C, 25±12°C slowed development time and led to an increase in pre-pupal mass, although these changes did not translate into any effects on longevity or fecundity at the adult stage. These findings indicate that environmental effects can extend across developmental stages despite the modularity of moth development but also highlight that there are few fitness consequences of the most variable thermal conditions likely to be experienced by Plutella xylostella.

  16. Influence of irreversible losses on the performance of a two-stage magnetic Brayton refrigeration cycle

    International Nuclear Information System (INIS)

    The general performance characteristics of a two-stage magnetic Brayton refrigeration cycle consisting of three constant magnetic fields and three irreversible adiabatic processes are investigated. Based on the thermodynamic properties of a magnetic material and the irreversible cycle model of a two-stage Brayton refrigerator, expressions for the cooling load and coefficient of performance of the refrigeration system are derived. The influence of the finite-rate heat transfer in the heat exchange processes, irreversibilities in the three adiabatic processes, ratios of two magnetic fields in the three constant magnetic field processes, and heat leak losses between two heat reservoirs on the performance of the two-stage magnetic Brayton refrigeration cycle are analyzed in detail. Some important performance curves, which can reveal the general characteristics of the refrigeration system, are presented and the maximum values of cooling load and coefficient of performance are numerically calculated. The optimal choices and matches of other parameters at the maximum cooling load or the maximum coefficient of performance are discussed and the optimally operating regions of some important parameters in the refrigeration system are determined. The results obtained here are compared with those derived from other models of the magnetic Brayton refrigeration cycles, and consequently, the advantage of an inter-cooled process is expounded.

  17. Cell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression.

    Directory of Open Access Journals (Sweden)

    Mathieu Dalvai

    Full Text Available Antiestrogens are designed to antagonize hormone induced proliferation and ERalpha target gene expression in mammary tumor cells. Commonly used drugs such as OH-Tamoxifen and ICI 182780 (Fulvestrant block cell cycle progression in G0/G1. Inversely, the effect of cell cycle stage on ER regulated gene expression has not been tested directly. We show that in ERalpha-positive breast cancer cells (MCF-7 the estrogen receptor gene and downstream target genes are cell cycle regulated with expression levels varying as much as three-fold between phases of the cell cycle. Steroid free culture conditions commonly used to assess the effect of hormones or antiestrogens on gene expression also block MCF-7 cells in G1-phase when several ERalpha target genes are overexpressed. Thus, cell cycle effects have to be taken into account when analyzing the impact of hormonal treatments on gene transcription. We found that antiestrogens repress transcription of several ERalpha target genes specifically in S phase. This observation corroborates the more rapid and strong impact of antiestrogen treatments on cell proliferation in thymidine, hydroxyurea or aphidicolin arrested cells and correlates with an increase of apoptosis compared to similar treatments in lovastatin or nocodazol treated cells. Hence, cell cycle effects synergize with the action of antiestrogens. An interesting therapeutic perspective could be to enhance the action of anti-estrogens by associating hormone-therapy with specific cell cycle drugs.

  18. Managing of economic potential of the enterprise at different stages of its life cycle

    Directory of Open Access Journals (Sweden)

    O.I. Maslak

    2014-03-01

    reserves its potential. The fluctuations of the environment and the corresponding internal characteristics of enterprises form the stage of the business cycle, in which the processes of formation, development and utilization potentialare occur. At the same time, management capacity should be in the light of these stages of the life cycle that aims to provide adaptability and efficiency of the company. Thus, an urgent task today is to organize management processes and economic potential businesses considering climate stages of its life cycle. In the life cycle climate offer the sum of the intrinsic characteristics on some stage considering of the environmental factors that have a significant impact on the entity. In the article the main priority areas of capacity on each stage of the life cycle and ways to implement them were suggested. At each stage of the life cycle program of strategic development and program activities are allocated. In this first group are more far-reaching programs for the long term, they aim to develop the existing activities of the company in the future, expand markets and gain leadership in the field of actual entities. Applications of the second group are designed for a short term, their goal is to maximize income at current economic conditions. The choice of such programs or shows a desire guidance in the near future to change the profile of the company, access to new products or insolvency of the entity the further development in this area of activity. The choice of a development program depends on the stage of the life cycle of an enterprise, hidden reserve capacity and ability of the company to quickly activate. Conclusions and directions of further researches. Thus, the constant fluctuation of the environment necessitate the development of control mechanisms that would provide an opportunity to identify and activate reserves passive potential for successful implementation of enterprise development programs, priority in climate certain stages

  19. TWO-STAGE ORDERING DECISION FOR A SHORT-LIFE-CYCLE PRODUCT

    Institute of Scientific and Technical Information of China (English)

    Bin LIU; Jian CHEN; Shu WU; Sifeng LIU

    2006-01-01

    This paper investigates the ordering decision problem for a short-life-cycle product under Bayesian updating. For a product characterized by a single manufacturing cycle and two selling periods, we depict a Two-Stage (TS) ordering strategy with a stochastic dynamic programming model in the view of the whole system, and prove that the expected profit function of the whole system is concave on the first ordering quantity and the remedial ordering quantity, respectively. Then, the optimal ordering decision is developed. Finally, characteristics of the optimal ordering quantities are analyzed with several examples. Our results show that the suggested TS decision model is better than a Quick Response (QR) decision model.

  20. Stages of Small Cell Lung Cancer

    Science.gov (United States)

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  1. Cell cycle variation in x-ray survival for cells from spheroids measured by volume cell sorting

    International Nuclear Information System (INIS)

    Considerable work has been done studying the variation in cell survival as a function of cell cycle position for monolayers or single cells exposed to radiation. Little is known about the effects of multicellular growth on the relative radiation sensitivity of cells in different cell cycle stages. The authors have developed a new technique for measuring the response of cells, using volume cell sorting, which is rapid, non-toxic, and does not require cell synchronization. By combining this technique with selective spheroid dissociation,they have measured the age response of cells located at various depths in EMT6 and Colon 26 spheroids. Although cells in the inner region had mostly G1-phase DNA contents, 15-20% had S- and G2-phase DNA contents. Analysis of these cells using BrdU labeling and flow cytometric analysis with a monoclonal antibody to BrdU indicated that the inner region cells were not synthesizing DNA. Thus, the authors were able to measure the radiation response of cells arrested in G1, S and G2 cell cycle phases. Comparison of inner and outer spheroid regions, and monolayer cultures, indicates that it is improper to extrapolate age response data in standard culture conditions to the situation in spheroids

  2. Hormone-dependence of sarin lethality in rats: Sex differences and stage of the estrous cycle

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Carl D., E-mail: carl.d.smith179.mil@mail.mil; Wright, Linnzi K.M.; Garcia, Gregory E.; Lee, Robyn B.; Lumley, Lucille A.

    2015-09-15

    Chemical warfare nerve agents (CWNAs) are highly toxic compounds that cause a cascade of symptoms and death, if exposed casualties are left untreated. Numerous rodent models have investigated the toxicity and mechanisms of toxicity of CWNAs, but most are limited to male subjects. Given the profound physiological effects of circulating gonadal hormones in female rodents, it is possible that the daily cyclical fluctuations of these hormones affect females' sensitivity to the lethal effects of CWNAs, and previous reports that included female subjects did not control for the stage of the hormonal cycle. The aim of the current study was to determine the 24-hour median lethal dose (LD{sub 50}) of the CWNA sarin in male, ovariectomized (OVEX) female, and female rats during different stages of the estrous cycle (diestrus, proestrus, and estrus). Additionally, baseline activity levels of plasma acetylcholinesterase, butyrylcholinesterase, and carboxylesterase were measured to determine differences among the groups. Results indicated that females in proestrus had a significantly higher LD{sub 50} of sarin compared to OVEX and estrous females. Although some sex differences were observed in the activity levels of plasma esterases, they were not consistent and likely not large enough to significantly affect the LD{sub 50}s. These results suggest that hormonal cyclicity can influence the outcome of CWNA-related studies using female rodents, and that this variability can be minimized by controlling for the stage of the cycle. Additional research is necessary to determine the precise mechanism of the observed differences because it is unlikely to be solely explained by plasma esterase activity. - Highlights: • The LD{sub 50} of sarin was determined in female rats throughout the stages of the estrous cycle. • Females in proestrus had a significantly higher LD{sub 50} compared to estrous or ovariectomized females. • No sex differences were observed between male and female

  3. Hormone-dependence of sarin lethality in rats: Sex differences and stage of the estrous cycle

    International Nuclear Information System (INIS)

    Chemical warfare nerve agents (CWNAs) are highly toxic compounds that cause a cascade of symptoms and death, if exposed casualties are left untreated. Numerous rodent models have investigated the toxicity and mechanisms of toxicity of CWNAs, but most are limited to male subjects. Given the profound physiological effects of circulating gonadal hormones in female rodents, it is possible that the daily cyclical fluctuations of these hormones affect females' sensitivity to the lethal effects of CWNAs, and previous reports that included female subjects did not control for the stage of the hormonal cycle. The aim of the current study was to determine the 24-hour median lethal dose (LD50) of the CWNA sarin in male, ovariectomized (OVEX) female, and female rats during different stages of the estrous cycle (diestrus, proestrus, and estrus). Additionally, baseline activity levels of plasma acetylcholinesterase, butyrylcholinesterase, and carboxylesterase were measured to determine differences among the groups. Results indicated that females in proestrus had a significantly higher LD50 of sarin compared to OVEX and estrous females. Although some sex differences were observed in the activity levels of plasma esterases, they were not consistent and likely not large enough to significantly affect the LD50s. These results suggest that hormonal cyclicity can influence the outcome of CWNA-related studies using female rodents, and that this variability can be minimized by controlling for the stage of the cycle. Additional research is necessary to determine the precise mechanism of the observed differences because it is unlikely to be solely explained by plasma esterase activity. - Highlights: • The LD50 of sarin was determined in female rats throughout the stages of the estrous cycle. • Females in proestrus had a significantly higher LD50 compared to estrous or ovariectomized females. • No sex differences were observed between male and female rats. • It is unlikely that

  4. Feedback and Modularity in Cell Cycle Control

    Science.gov (United States)

    Skotheim, Jan

    2009-03-01

    Underlying the wonderful diversity of natural forms is the ability of an organism to grow into its appropriate shape. Regulation ensures that cells grow, divide and differentiate so that the organism and its constitutive parts are properly proportioned and of suitable size. Although the size-control mechanism active in an individual cell is of fundamental importance to this process, it is difficult to isolate and study in complex multi-cellular systems and remains poorly understood. This motivates our use of the budding yeast model organism, whose Start checkpoint integrates multiple internal (e.g. cell size) and external signals into an irreversible decision to enter the cell cycle. We have endeavored to address the following two questions: What makes the Start transition irreversible? How does a cell compute its own size? I will report on the progress we have made. Our work is part of an emerging framework for understanding biological control circuits, which will allow us to discern the function of natural systems and aid us in engineering synthetic systems.

  5. Activation of the ribosomal RNA genes late in the third cell cycle of porcine embryos

    DEFF Research Database (Denmark)

    Viuff, Dorthe; Greve, Torben; Holm, Peter; Callesen, Henrik; Hyttel, Poul; Thomsen, Preben D

    2002-01-01

    In porcine embryos, nucleoli are first observed during the third postfertilization cell cycle, i.e., at the 4-cell stage. However, direct studies of the initiation of rRNA transcription have not been reported. This transcription was investigated in the present study by simultaneous visualization of...... electron microscopy. In general, the 2-cell and 4-cell embryos fixed at 10 and 20 h postcleavage (hpc) showed no signs of rRNA transcription. Four small clusters of fluorescein isothiocyanate (FITC) labeling were visible in interphase nuclei, consistent with hybridization to the rRNA gene clusters only...... phase during the third cell cycle....

  6. The steady-state transcriptome of the four major life-cycle stages of Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Orlando Ron

    2009-08-01

    Full Text Available Abstract Background Chronic chagasic cardiomyopathy is a debilitating and frequently fatal outcome of human infection with the protozoan parasite, Trypanosoma cruzi. Microarray analysis of gene expression during the T. cruzi life-cycle could be a valuable means of identifying drug and vaccine targets based on their appropriate expression patterns, but results from previous microarray studies in T. cruzi and related kinetoplastid parasites have suggested that the transcript abundances of most genes in these organisms do not vary significantly between life-cycle stages. Results In this study, we used whole genome, oligonucleotide microarrays to globally determine the extent to which T. cruzi regulates mRNA relative abundances over the course of its complete life-cycle. In contrast to previous microarray studies in kinetoplastids, we observed that relative transcript abundances for over 50% of the genes detected on the T. cruzi microarrays were significantly regulated during the T. cruzi life-cycle. The significant regulation of 25 of these genes was confirmed by quantitative reverse-transcriptase PCR (qRT-PCR. The T. cruzi transcriptome also mirrored published protein expression data for several functional groups. Among the differentially regulated genes were members of paralog clusters, nearly 10% of which showed divergent expression patterns between cluster members. Conclusion Taken together, these data support the conclusion that transcript abundance is an important level of gene expression regulation in T. cruzi. Thus, microarray analysis is a valuable screening tool for identifying stage-regulated T. cruzi genes and metabolic pathways.

  7. The Salmon Louse Lepeophtheirus salmonis (Copepoda: Caligidae life cycle has only two Chalimus stages.

    Directory of Open Access Journals (Sweden)

    Lars A Hamre

    Full Text Available Each year the salmon louse (Lepeophtheirussalmonis Krøyer, 1838 causes multi-million dollar commercial losses to the salmon farming industry world-wide, and strict lice control regimes have been put in place to reduce the release of salmon louse larvae from aquaculture facilities into the environment. For half a century, the Lepeophtheirus life cycle has been regarded as the only copepod life cycle including 8 post-nauplius instars as confirmed in four different species, including L. salmonis. Here we prove that the accepted life cycle of the salmon louse is wrong. By observations of chalimus larvae molting in incubators and by morphometric cluster analysis, we show that there are only two chalimus instars: chalimus 1 (comprising the former chalimus I and II stages which are not separated by a molt and chalimus 2 (the former chalimus III and IV stages which are not separated by a molt. Consequently the salmon louse life cycle has only six post-nauplius instars, as in other genera of caligid sea lice and copepods in general. These findings are of fundamental importance in experimental studies as well as for interpretation of salmon louse biology and for control and management of this economically important parasite.

  8. The Life Cycle Completed. Extended Version with New Chapters on the Ninth Stage of Development by Joan M. Erikson.

    Science.gov (United States)

    Erikson, Erik H.

    This expanded edition of a 1982 book by Erik Erikson summarizes his work on the stages of the human life cycle, including chapters on psychosexuality and the cycle of generations, major stages in psychosocial development, and ego and ethos. An additional chapter on the ninth stage sets forth his philosophy on old age--i.e. the 80s and 90s--and how…

  9. Resting stage cells of diatoms in deep waters in Kumano-

    OpenAIRE

    AKIRA, ISHIKAWA; Shingo, Kitami; Ken-Ichiro, Ishii; Toru, NAKAMURA; ICHIRO, IMAI

    2011-01-01

    The abundance and species composition of viable resting stage cells of diatoms were investigated in deep waters (200,500 and 1,000 m depths) collected at neighboring stations in Kumano-Nada, central part of Japan, in April, August and October 2006. Viable resting stage cells were enumerated by the modified extinction dilution method [most probable number (MPN) method] based on incubation. Resting stage cells were detected from all samples, except at 500 m depth in August, in a range of abunda...

  10. Stages of Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... immature teratomas , and malignant germ cell tumors: Mature Teratomas Mature teratomas are the most common type of ... that cause signs and symptoms of disease. Immature Teratomas Immature teratomas also usually occur in the sacrum ...

  11. Staging and imaging of small cell lung cancer

    OpenAIRE

    Kalemkerian, Gregory P.

    2011-01-01

    Abstract Small cell lung cancer (SCLC) has been primarily classified as limited or extensive, with limited stage confined to the primary tumor and regional lymph nodes. In the future, the TNM staging system should be integrated into the classification of SCLC. The appropriate staging work-up for patients with SCLC has traditionally included contrast-enhanced computed tomography (CT) scans of the chest and abdomen, bone scan, and magnetic resonance imaging or CT scan of the brain. Recent data ...

  12. Methodology of life cycle cost with risk expenditure for offshore process at conceptual design stage

    International Nuclear Information System (INIS)

    This study proposed a new LCC (life cycle cost) methodology with the risk expenditure taken into account for comparative evaluation of offshore process options at their conceptual design stage. The risk expenditure consisted of the failure risk expenditure and the accident risk expenditure. The former accounted for the production loss and the maintenance expense due to equipment failures while the latter reflected the asset damage and the fatality worth caused by disastrous accidents such as fire and explosion. It was demonstrated that the new LCC methodology was capable of playing the role of a process selection basis in choosing the best of the liquefaction process options including the power generation systems for a floating LNG (Liquefied natural gas) production facility. Without the risk expenditure, a simple economic comparison apparently favored the mixed refrigerant cycle which had the better efficiency. The new methodology with the risk expenditure, however, indicated that the nitrogen expansion cycle driven by steam turbines should be the optimum choice, mainly due to its better availability and safety. -- Highlights: → The study presented the methodology of the LCC with the risk expenditure for the conceptual design of offshore processes. → The proposed methodology demonstrated the applicability of the liquefaction unit with the power generation system of LNG FPSO. → Without the risk expenditure, a simple economic comparison apparently favored the mixed refrigerant cycle which had the better efficiency. → The new methodology indicated that the nitrogen expansion cycle driven by steam turbines is the optimum choice due to its better availability and safety.

  13. Organic Rankine Cycle recovering stage heat from MSF desalination distillate water

    International Nuclear Information System (INIS)

    Highlights: • The ORC model is validated against measured performance of an existing ORC unit. • This ORC model highlights the importance of refrigerant choice (R245fa performs better than R134a for this specific application). • For heat recovery from desalination plant, ORC evaporator and cooling water temperatures significantly influence the performance. - Abstract: This investigation addresses the potential for heat recovery from Multi Stage Flash (MSF) desalination plant hot distillate water to power an Organic Rankine Cycle (ORC), comparing R134a and R245fa refrigerants as the working fluid. Using design characteristics of an existing ORC unit, the model was first validated against its measured output. The distillate hot water from MSF stages is utilised to provide heat to the ORC and performance is investigated for both working fluids and for the number of MSF stages for heat recovery. For the specific MSF plant investigated, the net produced ORC power is found the highest with extraction up to MSF powering stage 8, generating 359 kW when R245fa is used and 307 kW when R134a is used. Both refrigerants exhibit an increase of power output and decrease of energy efficiency as heat is recovered from more MSF stages. The influence of variation of the evaporator and cooling temperature on ORC performance is demonstrated to be significant for both refrigerants, with R245fa performing better in this specific application

  14. A Novel Inflammation-Based Stage (I Stage) in Patients with Resectable Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Peng-Cheng Chen; Ji-Feng Feng

    2016-01-01

    Background. Inflammation plays a key role in cancer. In the current study, we proposed a novel inflammation-based stage, named I stage, for patients with resectable esophageal squamous cell carcinoma (ESCC). Methods. Three hundred and twenty-three patients with resectable ESCC were enrolled in the current study. The I stage was calculated as follows: patients with high levels of C-reactive protein (CRP) (>10 mg/L), neutrophil-to-lymphocyte ratio (NLR) (>3.5), and platelet-count-to-lymphocyte ...

  15. Influence of duration of fixation on the yield of chromosome aberrations in human lumphocyte culture exposed to γ-radiation at different mitotic cycle stages

    International Nuclear Information System (INIS)

    A comparative study was made of the yield of chromosome aberrations in human lymphocyte culture exposed to 60Co- γ-rays (2 Gy) at different mitotic cycle stages the cells being fixed after 52 and 60 hr. It was shown that with the latter fixation time (60 hr) the frequency of chromosome aberrations after irradiation in G1 stage was substantially lower than that with the former one (52 hr) and, vice versa, it was higher after irradiation in S and G2 stages. The authors discuss the probable causes of the distinctions observed

  16. Influence of duration of fixation on the yield of chromosome aberrations in human lumphocyte culture exposed to. gamma. -radiation at different mitotic cycle stages

    Energy Technology Data Exchange (ETDEWEB)

    Sevan' kaev, A.V.; Bogatykh, B.A.; Lychev, V.A. (Akademiya Meditsinskikh Nauk SSSR, Obninsk. Nauchno-Issledovatel' skij Inst. Meditsinskoj Radiologii)

    A comparative study was made of the yield of chromosome aberrations in human lymphocyte culture exposed to /sup 60/Co- ..gamma..-rays (2 Gy) at different mitotic cycle stages the cells being fixed after 52 and 60 hr. It was shown that with the latter fixation time (60 hr) the frequency of chromosome aberrations after irradiation in G/sub 1/ stage was substantially lower than that with the former one (52 hr) and, vice versa, it was higher after irradiation in S and G/sub 2/ stages. The authors discuss the probable causes of the distinctions observed.

  17. Test sequencing problem arising at the design stage for reducing life cycle cost

    Institute of Scientific and Technical Information of China (English)

    Zhang Shigang; Hu Zheng; Wen Xisen

    2013-01-01

    Previous test sequencing algorithms only consider the execution cost of a test at the application stage.Due to the fact that the placement cost of some tests at the design stage is considerably high compared with the execution cost,the sequential diagnosis strategy obtained by previous methods is actually not optimal from the view of life cycle.In this paper,the test sequencing problem based on life cycle cost is presented.It is formulated as an optimization problem,which is non-deterministic polynomial-time hard (NP-hard).An algorithm and a strategy to improve its computational efficiency are proposed.The formulation and algorithms are tested on various simulated systems and comparisons are made with the extant test sequencing methods.Application on a pump rotational speed control (PRSC) system of a spacecraft is studied in detail.Both the simulation results and the real-world case application results suggest that the solution proposed in this paper can significantly reduce the life cycle cost of a sequential fault diagnosis strategy.

  18. Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived from tumor cells at various malignant stages

    Energy Technology Data Exchange (ETDEWEB)

    Hoshiba, Takashi [Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510 (Japan); International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan); Tanaka, Masaru, E-mail: tanaka@yz.yamagata-u.ac.jp [Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510 (Japan)

    2013-09-20

    Highlights: •Models mimicking ECM in tumor with different malignancy were prepared. •Cancer cell proliferation was suppressed on benign tumor ECM. •Benign tumor cell proliferation was suppressed on cancerous ECM. •Chemoresistance of cancer cell was enhanced on cancerous ECM. -- Abstract: Extracellular matrix (ECM) has been focused to understand tumor progression in addition to the genetic mutation of cancer cells. Here, we prepared “staged tumorigenesis-mimicking matrices” which mimic in vivo ECM in tumor tissue at each malignant stage to understand the roles of ECM in tumor progression. Breast tumor cells, MDA-MB-231 (invasive), MCF-7 (non-invasive), and MCF-10A (benign) cells, were cultured to form their own ECM beneath the cells and formed ECM was prepared as staged tumorigenesis-mimicking matrices by decellularization treatment. Cells showed weak attachment on the matrices derived from MDA-MB-231 cancer cells. The proliferations of MDA-MB-231 and MCF-7 was promoted on the matrices derived from MDA-MB-231 cancer cells whereas MCF-10A cell proliferation was not promoted. MCF-10A cell proliferation was promoted on the matrices derived from MCF-10A cells. Chemoresistance of MDA-MB-231 cells against 5-fluorouracil increased on only matrices derived from MDA-MB-231 cells. Our results showed that the cells showed different behaviors on staged tumorigenesis-mimicking matrices according to the malignancy of cell sources for ECM preparation. Therefore, staged tumorigenesis-mimicking matrices might be a useful in vitro ECM models to investigate the roles of ECM in tumor progression.

  19. A Src inhibitor regulates the cell cycle of human pluripotent stem cells and improves directed differentiation.

    Science.gov (United States)

    Chetty, Sundari; Engquist, Elise N; Mehanna, Elie; Lui, Kathy O; Tsankov, Alexander M; Melton, Douglas A

    2015-09-28

    Driving human pluripotent stem cells (hPSCs) into specific lineages is an inefficient and challenging process. We show that a potent Src inhibitor, PP1, regulates expression of genes involved in the G1 to S phase transition of the cell cycle, activates proteins in the retinoblastoma family, and subsequently increases the differentiation propensities of hPSCs into all three germ layers. We further demonstrate that genetic suppression of Src regulates the activity of the retinoblastoma protein and enhances the differentiation potential of hPSCs across all germ layers. These positive effects extend beyond the initial germ layer specification and enable efficient differentiation at subsequent stages of differentiation. PMID:26416968

  20. Molecular biological mechanism II. Molecular mechanisms of cell cycle regulation

    International Nuclear Information System (INIS)

    The cell cycle in eukaryotes is regulated by central cell cycle controlling protein kinase complexes. These protein kinase complexes consist of a catalytic subunit from the cyclin-dependent protein kinase family (CDK), and a regulatory subunit from the cyclin family. Cyclins are characterised by their periodic cell cycle related synthesis and destruction. Each cell cycle phase is characterised by a specific set of CDKs and cyclins. The activity of CDK/cyclin complexes is mainly regulated on four levels. It is controlled by specific phosphorylation steps, the synthesis and destruction of cyclins, the binding of specific inhibitor proteins, and by active control of their intracellular localisation. At several critical points within the cell cycle, named checkpoints, the integrity of the cellular genome is monitored. If damage to the genome or an unfinished prior cell cycle phase is detected, the cell cycle progression is stopped. These cell cycle blocks are of great importance to secure survival of cells. Their primary importance is to prevent the manifestation and heritable passage of a mutated genome to daughter cells. Damage sensing, DNA repair, cell cycle control and apoptosis are closely linked cellular defence mechanisms to secure genome integrity. Disregulation in one of these defence mechanisms are potentially correlated with an increased cancer risk and therefore in at least some cases with an increased radiation sensitivity. (orig.)

  1. Circulating Tumor DNA in Predicting Outcomes in Patients With Stage IV Head and Neck Cancer or Stage III-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-04-11

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  2. Revealing the cellular localization of STAT1 during the cell cycle by super-resolution imaging

    Science.gov (United States)

    Gao, Jing; Wang, Feng; Liu, Yanhou; Cai, Mingjun; Xu, Haijiao; Jiang, Junguang; Wang, Hongda

    2015-03-01

    Signal transducers and activators of transcription (STATs) can transduce cytokine signals and regulate gene expression. The cellular localization and nuclear trafficking of STAT1, a representative of the STAT family with multiple transcriptional functions, is tightly related with transcription process, which usually happens in the interphase of the cell cycle. However, these priority questions regarding STAT1 distribution and localization at the different cell-cycle stages remain unclear. By using direct stochastic optical reconstruction microscopy (dSTORM), we found that the nuclear expression level of STAT1 increased gradually as the cell cycle carried out, especially after EGF stimulation. Furthermore, STAT1 formed clusters in the whole cell during the cell cycle, with the size and the number of clusters also increasing significantly from G1 to G2 phase, suggesting that transcription and other cell-cycle related activities can promote STAT1 to form more and larger clusters for fast response to signals. Our work reveals that the cellular localization and clustering distribution of STAT1 are associated with the cell cycle, and further provides an insight into the mechanism of cell-cycle regulated STAT1 signal transduction.

  3. THE EFFICIENCY OF PROMOTIONAL INSTRUMENTS RELATED TO THE PRODUCT LIFE CYCLE STAGES

    Directory of Open Access Journals (Sweden)

    MIHAELA MARCU

    2010-01-01

    Full Text Available Regarded as a planning tool, PLC (product life cycle strongly contributes to the identification of the main marketing challenges that may arise throughout the life of a product/service. Thus, the marketing management has the opportunity to develop and implement those solutions designed to optimize each of the 4P of marketing mix: product (quality, price, distribution (placement and promotion. The communication program has an essential role, because the company presents through it its "product" to actual or potential customers in order to convince them of the benefits of purchasing/using it. The efficiency of the promotional instruments involves an appropriate allocation of funds needed to promote the product/service in relation to the stage of its life cycle.

  4. Cell-cycle-independent transitions in temporal identity of mammalian neural progenitor cells

    Science.gov (United States)

    Okamoto, Mayumi; Miyata, Takaki; Konno, Daijiro; Ueda, Hiroki R.; Kasukawa, Takeya; Hashimoto, Mitsuhiro; Matsuzaki, Fumio; Kawaguchi, Ayano

    2016-01-01

    During cerebral development, many types of neurons are sequentially generated by self-renewing progenitor cells called apical progenitors (APs). Temporal changes in AP identity are thought to be responsible for neuronal diversity; however, the mechanisms underlying such changes remain largely unknown. Here we perform single-cell transcriptome analysis of individual progenitors at different developmental stages, and identify a subset of genes whose expression changes over time but is independent of differentiation status. Surprisingly, the pattern of changes in the expression of such temporal-axis genes in APs is unaffected by cell-cycle arrest. Consistent with this, transient cell-cycle arrest of APs in vivo does not prevent descendant neurons from acquiring their correct laminar fates. Analysis of cultured APs reveals that transitions in AP gene expression are driven by both cell-intrinsic and -extrinsic mechanisms. These results suggest that the timing mechanisms controlling AP temporal identity function independently of cell-cycle progression and Notch activation mode. PMID:27094546

  5. The cell cycle of the planctomycete Gemmata obscuriglobus with respect to cell compartmentalization

    Directory of Open Access Journals (Sweden)

    Fuerst John A

    2009-01-01

    well as DNA confirmed the behaviour of the nucleoid and nucleoid envelope during cell division. Electron microscopy of cryosubstituted cells confirmed deductions from light microscopy concerning nucleoid presence in relation to the stage of budding, and showed that the nucleoid was observed to occur in both mother and bud cells only at later budding stages. It further suggested that nucleoid envelope formed only after the nucleoid was translocated into the bud, since envelopes only appeared in more mature buds, while naked nucleoids occurred in smaller buds. Nucleoid envelope appeared to originate from the intracytoplasmic membranes (ICM of both mother cell and bud. There was always a connecting passage between mother cell and bud during the budding process until separation of the two cells. The division cycle of the nucleated planctomycete G. obscuriglobus appears to be a complex process in which chromosomal DNA is transported to the daughter cell bud after initial formation of the bud, and this can be performed repeatedly by a single mother cell. Conclusion The division cycle of the nucleated planctomycete G. obscuriglobus is a complex process in which chromosomal nucleoid DNA is transported to the daughter cell bud after initial formation of a bud without nucleoid. The new bud nucleoid is initially naked and not surrounded by membrane, but eventually acquires a complete nucleoid envelope consisting of two closely apposed membranes as occurs in the mother cell. The membranes of the new nucleoid envelope surrounding the bud nucleoid are derived from intracytoplasmic membranes of both the mother cell and the bud. The cell division of G. obscuriglobus displays some unique features not known in cells of either prokaryotes or eukaryotes.

  6. The ubiquitin-proteasome system in glioma cell cycle control

    Directory of Open Access Journals (Sweden)

    Vlachostergios Panagiotis J

    2012-07-01

    Full Text Available Abstract A major determinant of cell fate is regulation of cell cycle. Tight regulation of this process is lost during the course of development and progression of various tumors. The ubiquitin-proteasome system (UPS constitutes a universal protein degradation pathway, essential for the consistent recycling of a plethora of proteins with distinct structural and functional roles within the cell, including cell cycle regulation. High grade tumors, such as glioblastomas have an inherent potential of escaping cell cycle control mechanisms and are often refractory to conventional treatment. Here, we review the association of UPS with several UPS-targeted proteins and pathways involved in regulation of the cell cycle in malignant gliomas, and discuss the potential role of UPS inhibitors in reinstitution of cell cycle control.

  7. Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

    Science.gov (United States)

    2016-05-02

    Advanced Pleural Malignant Mesothelioma; HLA-A*0201 Positive Cells Present; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pleural Malignant Mesothelioma; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pleural Mesothelioma

  8. Desiccation sensitivity and cell cycle aspects in seeds of Inga vera subsp. affinis

    NARCIS (Netherlands)

    Faria, J.M.R.; Lammeren, van A.A.M.; Hilhorst, H.W.M.

    2004-01-01

    The desiccation sensitivity of seeds of Inga vera Willd. subsp. affinis, a recalcitrant-seeded tree from Brazil, was analysed, focusing on water relations and cell-cycle aspects, including DNA content and the microtubular cytoskeleton. Seeds were collected at four developmental stages, dried to diff

  9. The improvement of approaches to marketing testing of ecological innovative products in the stages of innovative cycle

    OpenAIRE

    Ye.I. Nagornyi; T.V. Kasianenko

    2013-01-01

    The aim of the article. The aim of the article is theoretical justification and improvement of approaches to marketing testing of ecological innovative production in the stages of innovative cycle, and the sequence of decision-making procedures on its readiness to entry into the market by results of testing. The results of the analysis. Launch of the ecological innovative products on the market and providing its passage through the stages of the innovative cycle requires continuous and hig...

  10. First Law Analysis of a Two-stage Ejector-vapor Compression Refrigeration Cycle working with R404A

    OpenAIRE

    Feiza Memet; Daniela-Elena Mitu

    2011-01-01

    The traditional two-stage vapor compression refrigeration cycle might be replaced by a two-stage ejector-vapor compression refrigeration cycle if it is aimed the decrease of irreversibility during expansion. In this respect, the expansion valve is changed with an ejector. The performance improvement is searched in the case of choosing R404A as a refrigerant. Using the ejector as an expansion device ensures a higher value for COP compared to the traditional case. On the basis...

  11. Thermodynamics analysis of a modified dual-evaporator CO2 transcritical refrigeration cycle with two-stage ejector

    International Nuclear Information System (INIS)

    In this paper, a modified dual-evaporator CO2 transcritical refrigeration cycle with two-stage ejector (MDRC) is proposed. In MDRC, the two-stage ejector are employed to recover the expansion work from cycle throttling processes and enhance the system performance and obtain dual-temperature refrigeration simultaneously. The effects of some key parameters on the thermodynamic performance of the modified cycle are theoretically investigated based on energetic and exergetic analyses. The simulation results for the modified cycle show that two-stage ejector exhibits more effective system performance improvement than the single ejector in CO2 dual-temperature refrigeration cycle, and the improvements of the maximum system COP (coefficient of performance) and system exergy efficiency could reach 37.61% and 31.9% over those of the conventional dual-evaporator cycle under the given operating conditions. The exergetic analysis for each component at optimum discharge pressure indicates that the gas cooler, compressor, two-stage ejector and expansion valves contribute main portion to the total system exergy destruction, and the exergy destruction caused by the two-stage ejector could amount to 16.91% of the exergy input. The performance characteristics of the proposed cycle show its promise in dual-evaporator refrigeration system. - Highlights: • Two-stage ejector is used in dual-evaporator CO2 transcritical refrigeration cycle. • Energetic and exergetic methods are carried out to analyze the system performance. • The modified cycle could obtain dual-temperature refrigeration simultaneously. • Two-stage ejector could effectively improve system COP and exergy efficiency

  12. A cell cycle timer for asymmetric spindle positioning.

    Directory of Open Access Journals (Sweden)

    Erin K McCarthy Campbell

    2009-04-01

    Full Text Available The displacement of the mitotic spindle to one side of a cell is important for many cells to divide unequally. While recent progress has begun to unveil some of the molecular mechanisms of mitotic spindle displacement, far less is known about how spindle displacement is precisely timed. A conserved mitotic progression mechanism is known to time events in dividing cells, although this has never been linked to spindle displacement. This mechanism involves the anaphase-promoting complex (APC, its activator Cdc20/Fizzy, its degradation target cyclin, and cyclin-dependent kinase (CDK. Here we show that these components comprise a previously unrecognized timer for spindle displacement. In the Caenorhabditis elegans zygote, mitotic spindle displacement begins at a precise time, soon after chromosomes congress to the metaphase plate. We found that reducing the function of the proteasome, the APC, or Cdc20/Fizzy delayed spindle displacement. Conversely, inactivating CDK in prometaphase caused the spindle to displace early. The consequence of experimentally unlinking spindle displacement from this timing mechanism was the premature displacement of incompletely assembled components of the mitotic spindle. We conclude that in this system, asymmetric positioning of the mitotic spindle is normally delayed for a short time until the APC inactivates CDK, and that this delay ensures that the spindle does not begin to move until it is fully assembled. To our knowledge, this is the first demonstration that mitotic progression times spindle displacement in the asymmetric division of an animal cell. We speculate that this link between the cell cycle and asymmetric cell division might be evolutionarily conserved, because the mitotic spindle is displaced at a similar stage of mitosis during asymmetric cell divisions in diverse systems.

  13. Update in non small- cell lung cancer staging

    OpenAIRE

    Salgado, RA; Snoeckx, A.; Spinhoven, M; Beeck, B Op de; Corthouts, B; Parizel, PM

    2013-01-01

    Significant progress has been made with the introduction of the TNM-7 staging system for non-small cell lung cancer (NSCLC). Constituting the first major revision in 12 years, the seventh edition of NSCLC TNM (TNM-7) is based on the recommendations from the International Association for the Study of Lung Cancer (IASLC) Lung Cancer Staging Project of 2007. This new TNM iteration includes a subset analysis on SCLC and carcinoid tumors.A thorough understanding of its principles by the radiologis...

  14. Staging of Cervical Lymph Nodes in Oral Squamous Cell Carcinoma

    DEFF Research Database (Denmark)

    Norling, Rikke; Buron, Birgitte Marie Due; Therkildsen, Marianne Hamilton;

    2014-01-01

    INTRODUCTION: Clinical staging of patients with oral squamous cell carcinoma (OSCC) is crucial for the choice of treatment. Computed tomography (CT) and/or magnetic resonance imaging (MRI) are typically recommended and used for staging of the cervical lymph nodes (LNs). Although ultrasonography (US...... patients (6%) were over-staged by US. CONCLUSION: The addition of US to the clinical work-up of patients with cN0 OSCC increases the detection of metastases, thus US potentially reduces the number of patients requiring a secondary neck surgery after sentinel node biopsy....

  15. Limit Cycle Oscillations in Pacemaker Cells

    CERN Document Server

    Endresen, L P; Endresen, Lars Petter; Skarland, Nils

    1999-01-01

    In recent decades, several mathematical models describing the pacemaker activity of the rabbit sinoatrial node have been developed. We demonstrate that it is not possible to establish the existence, uniqueness, and stability of a limit cycle oscillation in those models. Instead we observe an infinite number of limit cycles. We then display numerical results from a new model, with a limit cycle that can be reached from many different initial conditions.

  16. Ocean acidification affects redox-balance and ion-homeostasis in the life-cycle stages of Emiliania huxleyi.

    Directory of Open Access Journals (Sweden)

    Sebastian D Rokitta

    Full Text Available Ocean Acidification (OA has been shown to affect photosynthesis and calcification in the coccolithophore Emiliania huxleyi, a cosmopolitan calcifier that significantly contributes to the regulation of the biological carbon pumps. Its non-calcifying, haploid life-cycle stage was found to be relatively unaffected by OA with respect to biomass production. Deeper insights into physiological key processes and their dependence on environmental factors are lacking, but are required to understand and possibly estimate the dynamics of carbon cycling in present and future oceans. Therefore, calcifying diploid and non-calcifying haploid cells were acclimated to present and future CO(2 partial pressures (pCO(2; 38.5 Pa vs. 101.3 Pa CO(2 under low and high light (50 vs. 300 µmol photons m(-2 s(-1. Comparative microarray-based transcriptome profiling was used to screen for the underlying cellular processes and allowed to follow up interpretations derived from physiological data. In the diplont, the observed increases in biomass production under OA are likely caused by stimulated production of glycoconjugates and lipids. The observed lowered calcification under OA can be attributed to impaired signal-transduction and ion-transport. The haplont utilizes distinct genes and metabolic pathways, reflecting the stage-specific usage of certain portions of the genome. With respect to functionality and energy-dependence, however, the transcriptomic OA-responses resemble those of the diplont. In both life-cycle stages, OA affects the cellular redox-state as a master regulator and thereby causes a metabolic shift from oxidative towards reductive pathways, which involves a reconstellation of carbon flux networks within and across compartments. Whereas signal transduction and ion-homeostasis appear equally OA-sensitive under both light intensities, the effects on carbon metabolism and light physiology are clearly modulated by light availability. These interactive effects

  17. Accuracy of preoperative CT T staging of renal cell carcinoma: which features predict advanced stage?

    International Nuclear Information System (INIS)

    Aims: To characterise CT findings in renal cell carcinoma (RCC), and establish which features are associated with higher clinical T stage disease, and to evaluate patterns of discrepancy between radiological and pathological staging of RCC. Materials and methods: Preoperative CT studies of 92 patients with 94 pathologically proven RCCs were retrospectively reviewed. CT stage was compared with pathological stage using the American Joint Committee on Cancer (AJCC), 7th edition (2010). The presence or absence of tumour necrosis, perinephric fat standing, thickening of Gerota's fascia, collateral vessels were noted, and correlated with pT stage. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) for predicting pT stage ≥pT3a were derived separately for different predictors using cross-tabulations. Results: Twenty-four lesions were pathological stage T1a, 21 were T1b, seven were T2a, 25 were T3a, 11 were T3b, four were T3c, and two were T4. There were no stage T2b. Sixty-three (67%) patients had necrosis, 27 (29%) thickening of Gerota's fascia (1 T1a), 25 had collateral vessels (0 T1a), 28 (30%) had fat stranding of <2 mm, 20 (21%) of 2–5mm and one (1%) of >5 mm. For pT stage ≥pT3a, the presence of perinephric fat stranding had a sensitivity, specificity, PPV and NPV of 74%, 65%, 63%, and 76%, respectively. Presence of tumour necrosis had a sensitivity, specificity, PPV, and NPV of 81%, 44%, 54%, and 72%, respectively. Thickening of Gerota's fascia had a sensitivity, specificity, PPV, and NPV of 52%, 90%, 81% and 70%, respectively; and enlarged collateral vessels had a sensitivity, specificity, PPV, and NPV value of 52%, 94%, 88%, and 71% respectively. Conclusion: The presence of perinephric stranding and tumour necrosis were not reliable signs for pT stage >T3a. Thickening of Gerota's fascia and the presence of collateral vessels in the peri- or paranephric fat had 90% and 94% specificity, with 82% and 88

  18. Systems Level Modeling of the Cell Cycle Using Budding Yeast

    Directory of Open Access Journals (Sweden)

    D.R. Kim

    2007-01-01

    Full Text Available Proteins involved in the regulation of the cell cycle are highly conserved across all eukaryotes, and so a relatively simple eukaryote such as yeast can provide insight into a variety of cell cycle perturbations including those that occur in human cancer. To date, the budding yeast Saccharomyces cerevisiae has provided the largest amount of experimental and modeling data on the progression of the cell cycle, making it a logical choice for in-depth studies of this process. Moreover, the advent of methods for collection of high-throughput genome, transcriptome, and proteome data has provided a means to collect and precisely quantify simultaneous cell cycle gene transcript and protein levels, permitting modeling of the cell cycle on the systems level. With the appropriate mathematical framework and suffi cient and accurate data on cell cycle components, it should be possible to create a model of the cell cycle that not only effectively describes its operation, but can also predict responses to perturbations such as variation in protein levels and responses to external stimuli including targeted inhibition by drugs. In this review, we summarize existing data on the yeast cell cycle, proteomics technologies for quantifying cell cycle proteins, and the mathematical frameworks that can integrate this data into representative and effective models. Systems level modeling of the cell cycle will require the integration of high-quality data with the appropriate mathematical framework, which can currently be attained through the combination of dynamic modeling based on proteomics data and using yeast as a model organism.

  19. WNT5A modulates cell cycle progression and contributes to the chemoresistance in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    Wei Wei; Hui-Hui Sun; Na Li; Hong-Yue Li; Xin Li; Qiang Li; Xiao-Hong Shen

    2014-01-01

    BACKGROUND: Although there are many studies on the mechanism of chemoresistance in cancers, studies on the relations between WNT5A and chemoresistance in pancreatic cancer are rare. The present study was to examine the role of WNT5A in the regulation of cell cycle progression and in chemoresistance in pancreatic cancer tissues and cell lines. METHODS: Fresh pancreatic cancer and paracarcinoma tissues were obtained from 32 patients. The expressions of WNT5A, AKT/p-AKT and Cyclin D1 were detected by immunohistochemistry, and the correlation between WNT5A expression and clinicopathological characteristics was analyzed. The relationship between WNT5A expression and gemcitabine resistance was studied in PANC-1 and MIAPaCa2 cell lines. The effect of WNT5A on the regulation of cell cycle and gemcitabine cytotoxicity were investigated. The associations among the expressions of p-AKT, Cyclin D1 and WNT5A were also analyzed in cell lines and the effect of WNT5A on restriction-point (R-point) progression was evaluated. RESULTS: WNT5A, p-AKT and Cyclin D1 were highly expressed in pancreatic cancer tissues, and the WNT5A expression was correlated with the TNM stages. In vitro, WNT5A expression was associated with gemcitabine chemoresistance. The percentage of cells was increased in G0/G1 phase and decreased in S phase after knockdown of WNT5A in PANC-1. WNT5A promoted Cyclin D1 expression through phosphorylation of AKT which consequently enhanced G1-S transition and gemcitabine resistance. Furthermore, WNT5A enhanced the cell cycle progression toward R-point through regulation of retinoblastoma protein (pRb) and pRb-E2F complex formation. CONCLUSIONS: WNT5A induced chemoresistance by regulation of G1-S transition in pancreatic cancer cells. WNT5A might serve as a predictor of gemcitabine response and as a potential target for tumor chemotherapy.

  20. Magnetocaloric cycle with six stages: Possible application of graphene at low temperature

    International Nuclear Information System (INIS)

    The present work proposes a thermodynamic hexacycle based on the magnetocaloric oscillations of graphene, which has either a positive or negative adiabatic temperature change depending on the final value of the magnetic field change. For instance, for graphenes at 25 K, an applied field of 2.06 T/1.87 T promotes a temperature change of ca. −25 K/+3 K. The hexacycle is based on the Brayton cycle and instead of the usual four steps, it has six stages, taking advantage of the extra cooling provided by the inverse adiabatic temperature change. This proposal opens doors for magnetic cooling applications at low temperatures

  1. The Cell Cycle: An Activity Using Paper Plates to Represent Time Spent in Phases of the Cell Cycle

    Science.gov (United States)

    Scherer, Yvette D.

    2014-01-01

    In this activity, students are given the opportunity to combine skills in math and geometry for a biology lesson in the cell cycle. Students utilize the data they collect and analyze from an online onion-root-tip activity to create a paper-plate time clock representing a 24-hour cell cycle. By dividing the paper plate into appropriate phases of…

  2. Magnetic resonance imaging in the staging of renal cell carcinoma

    International Nuclear Information System (INIS)

    Eighteen patients with renal neoplasm underwent magnetic resonance imaging (MRI) using a 1.5 Tesla superconducting magnetic system and spin echo images were obtained by quick scan technique under holding breath. MR images were interpreted independently of the computerized tomography (CT) findings. The preoperative stagings of the 18 renal carcinomas, as judged by MRI, were compared with those obtained at laparotomy. The anatomic staging was correctly performed by MRI in 13 patients (72 %). In the patients who had intrarenal small tumor with normal renal contour, MRI demonstrated a solid mass clearly distinguishable from surrounding renal parenchyma using the paramagnetic contrast agent (gadolinium-DTPA). When compared with results of evaluation by CT in staging, MRI appeared to have several advantages in determination of whole mass; the detection of tumor thrombus into renal vein and inferior vena cava; and the evaluation of direct tumor invasion of adjacent organs. MRI should play an important role in the staging of renal cell carcinoma. (author)

  3. Low Doses of Cisplatin Induce Gene Alterations, Cell Cycle Arrest, and Apoptosis in Human Promyelocytic Leukemia Cells.

    Science.gov (United States)

    Velma, Venkatramreddy; Dasari, Shaloam R; Tchounwou, Paul B

    2016-01-01

    Cisplatin is a known antitumor drug, but its mechanisms of action are not fully elucidated. In this research, we studied the anticancer potential of cisplatin at doses of 1, 2, or 3 µM using HL-60 cells as a test model. We investigated cisplatin effects at the molecular level using RNA sequencing, cell cycle analysis, and apoptotic assay after 24, 48, 72, and 96 hours of treatment. The results show that many genes responsible for molecular and cellular functions were significantly altered. Cisplatin treatment also caused the cells to be arrested at the DNA synthesis phase, and as the time increases, the cells gradually accumulated at the sub-G1 phase. Also, as the dose increases, a significant number of cells entered into the apoptotic and necrotic stages. Altogether, the data show that low doses of cisplatin significantly impact the viability of HL-60 cells, through modulation of gene expression, cell cycle, and apoptosis. PMID:27594783

  4. Cell Cycle Related Differentiation of Bone Marrow Cells into Lung Cells

    Energy Technology Data Exchange (ETDEWEB)

    Dooner, Mark; Aliotta, Jason M.; Pimental, Jeffrey; Dooner, Gerri J.; Abedi, Mehrdad; Colvin, Gerald; Liu, Qin; Weier, Heinz-Ulli; Dooner, Mark S.; Quesenberry, Peter J.

    2007-12-31

    Green-fluorescent protein (GFP) labeled marrow cells transplanted into lethally irradiated mice can be detected in the lungs of transplanted mice and have been shown to express lung specific proteins while lacking the expression of hematopoietic markers. We have studied marrow cells induced to transit cell cycle by exposure to IL-3, IL-6, IL-11 and steel factor at different times of culture corresponding to different phases of cell cycle. We have found that marrow cells at the G1/S interface have a 3-fold increase in cells which assume a lung phenotype and that this increase is no longer seen in late S/G2. These cells have been characterized as GFP{sup +} CD45{sup -} and GFP{sup +} cytokeratin{sup +}. Thus marrow cells with the capacity to convert into cells with a lung phenotype after transplantation show a reversible increase with cytokine induced cell cycle transit. Previous studies have shown the phenotype of bone marrow stem cells fluctuates reversibly as these cells traverse cell cycle, leading to a continuum model of stem cell regulation. The present studies indicate that marrow stem cell production of nonhematopoietic cells also fluctuates on a continuum.

  5. Humanized Mouse Models to Study Cell-Mediated Immune Responses to Liver-Stage Malaria Vaccines.

    Science.gov (United States)

    Good, Michael F; Hawkes, Michael T; Yanow, Stephanie K

    2015-11-01

    Malaria vaccine development is hampered by the lack of small animal models that recapitulate human immune responses to Plasmodium falciparum. We review the burgeoning literature on humanized mice for P. falciparum infection, including challenges in engraftment of human immune cells, hepatocytes, and erythrocytes. Recent advances in immune-compromised mouse models and stem cell technology have already enabled proof of concept that the entire parasite life cycle can be sustained in a murine model and that adaptive human immune responses to several parasite stages can be measured. Nonetheless, optimization is needed to achieve a reproducible and relevant murine model for malaria vaccine development. This review is focused on the complexities of T cell development in a mouse humanized with both a lymphoid system and hepatocytes. An understanding of this will facilitate the use of humanized mice in the development of liver-stage vaccines. PMID:26458783

  6. CDK inhibitors, p21Cip1 and p27Kip1, participate in cell cycle exit of mammalian cardiomyocytes

    International Nuclear Information System (INIS)

    Highlights: •Expression of p21 and p27 in the hearts showed a peak during postnatal stages. •p21 and p27 bound to cyclin E, cyclin A and CDK2 in the hearts at postnatal stages. •Cardiomyocytes in both KO mice showed failure in the cell cycle exit at G1-phase. •These data show the first apparent phenotypes in the hearts of Cip/Kip KO mice. -- Abstract: Mammalian cardiomyocytes actively proliferate during embryonic stages, following which cardiomyocytes exit their cell cycle after birth. The irreversible cell cycle exit inhibits cardiac regeneration by the proliferation of pre-existing cardiomyocytes. Exactly how the cell cycle exit occurs remains largely unknown. Previously, we showed that cyclin E- and cyclin A-CDK activities are inhibited before the CDKs levels decrease in postnatal stages. This result suggests that factors such as CDK inhibitors (CKIs) inhibit CDK activities, and contribute to the cell cycle exit. In the present study, we focused on a Cip/Kip family, which can inhibit cyclin E- and cyclin A-CDK activities. Expression of p21Cip1 and p27Kip1 but not p57Kip2 showed a peak around postnatal day 5, when cyclin E- and cyclin A-CDK activities start to decrease. p21Cip1 and p27Kip1 bound to cyclin E, cyclin A and CDK2 at postnatal stages. Cell cycle distribution patterns of postnatal cardiomyocytes in p21Cip1 and p27Kip1 knockout mice showed failure in the cell cycle exit at G1-phase, and endoreplication. These results indicate that p21Cip1 and p27Kip play important roles in the cell cycle exit of postnatal cardiomyocytes

  7. In situ cell cycle phase determination using Raman spectroscopy

    Science.gov (United States)

    Oshima, Yusuke; Takenaka, Tatsuji; Sato, Hidetoshi; Furihata, Chie

    2010-02-01

    Raman spectroscopy is a powerful tool for analysis of the chemical composition in living tissue and cells without destructive processes such as fixation, immunostaining, and fluorescence labeling. Raman microspectroscopic technique enables us to obtain a high quality spectrum from a single living cell. We demonstrated in situ cell cycle analysis with Raman microspectroscopy with the excitation wavelength of 532 nm. Cell cycle phases, G0/G1 and G2/M were able to be identified in the present study. The result of in situ Raman analysis was evaluated with flow cytometry analysis. Although the Raman spectra of living cells showed complex patterns during cell cycle, several Raman bands could be useful as markers for the cell cycle identification. A single cell analysis using Raman microspectroscopy predicted a possibility to observe directly molecular dynamics intracellular molecules of proteins, lipids and nucleic acids. Our current study focused on cytoplasm region and resonant Raman signals of cytochrome c in mitochondrion, and discussed how the Raman signals from cellular components contribute to the Raman spectral changes in cell cycle change in the human living cell (lung cancer cell).

  8. The Late Stage of T Cell Development within Mouse Thymus

    Institute of Scientific and Technical Information of China (English)

    Weifeng Chen

    2004-01-01

    After positive selection and lineage commitment, the TCRαβ+CD4/CD8 SP medullary thymocytes migrate into and reside in thymic medulla, where they undergo an ordered program of late stage of T cell functional maturation and negative selection to delete self-reactive clones by apoptosis. Accomplishment of this final differentiation pathway, a physiological T cell repertoire is formed : T cells acquire immunocompetence to respond to foreign antigens and tolerance to self-antigens, ready for the emigration to homing to the T cell regions of peripheral lymphoid organs and tissues. In this review, emphases are put on introducing the approaches applied in this area and our own observations. Basically, we have analyzed the late stage of medullary thymocyte phenotypic differentiation pathways of both CD4 SP and CD8 SP medullary thymocytes and the concomitant functional maturation pathway, in particular, of CD4 SP thymocytes. It is to provide a standard to compare the functional capacity of the cells at the developmental stages induced by different conditions. The cellular and molecular basis of this differentiation process has been partially described. Cellular & Molecular Immunology. 2004;1(1):3-11.

  9. The Late Stage of T Cell Development within Mouse Thymus

    Institute of Scientific and Technical Information of China (English)

    WeifengChen

    2004-01-01

    After positive selection and lineage commitment, the TCRαβ+CD4/CD8 SP medullary thymocytes migrate into and reside in thymic medulla, where they undergo an ordered program of late stage of T cell functional maturation and negative selection to delete self-reactive clones by apoptosis. Accomplishment of this final differentiation pathway, a physiological T cell repertoire is formed: T cells acquire immunocompetence to respond to foreign antigens and tolerance to self-antigens, ready for the emigration to homing to the T cell regions of peripheral lymphoid organs and tissues. In this review, emphases are put on introducing the approaches applied in this area and our own observations. Basically, we have analyzed the late stage of medullary thymocyte phenotypic differentiation pathways of both CD4 SP and CD8 SP medullary thymocytes and the concomitant functional maturation pathway, in particular, of CD4 SP thymocytes. It is to provide a standard to compare the functional capacity of the cells at the developmental stages induced by different conditions. The cellular and molecular basis of this differentiation process has been partially described. Cellular & Molecular Immunology. 2004;1(1):3-11.

  10. Focus on Merkel cell carcinoma: diagnosis and staging

    Energy Technology Data Exchange (ETDEWEB)

    Grandhaye, Marion; Teixeira, Pedro Gondim; Blum, Alain [Imagerie Guilloz CHU de Nancy Hopital Central, Nancy (France); Henrot, Philippe [Service de Radiologie Institut de Cancerologie de Lorraine, Vandoeuvre les Nancy (France); Morel, Olivier [Medecine Nucleaire CHU Nancy Hopital Brabois, Vancoeuvre les Nancy (France); Sirveaux, Francois [Service de Chirurgie Centre chirurgical Emile Galle, Nancy (France); Verhaeghe, Jean-Luc [Service de Chirurgie Institut de Cancerologie de Lorraine, Vandoeuvre les Nancy (France)

    2015-06-01

    Merkel cell carcinoma is a rare lymphophilic skin tumor of neuroendocrine origin with the potential for rapid progression. Small, localized lesions are diagnosed and treated clinically, but advanced tumors often undergo imaging evaluation. Due to its rarity, radiologists are unaware of evocative imaging features and usually do not consider Merkel cell carcinoma in the differential diagnosis of soft tissue tumors. Appropriate staging is important to determine appropriate treatment and has an impact on patient prognosis. Multimodality imaging is usually needed, and there is no consensus on the optimal imaging strategy. The purpose of this article is to review various aspects of Merkel cell carcinoma imaging and look in detail at how optimal multimodality staging should be carried out. (orig.)

  11. Sea urchin akt activity is Runx-dependent and required for post-cleavage stage cell division

    KAUST Repository

    Robertson, Anthony J.

    2013-03-25

    In animal development following the initial cleavage stage of embryogenesis, the cell cycle becomes dependent on intercellular signaling and controlled by the genomically encoded ontogenetic program. Runx transcription factors are critical regulators of metazoan developmental signaling, and we have shown that the sea urchin Runx gene runt-1, which is globally expressed during early embryogenesis, functions in support of blastula stage cell proliferation and expression of the mitogenic genes pkc1, cyclinD, and several wnts. To obtain a more comprehensive list of early runt-1 regulatory targets, we screened a Strongylocentrotus purpuratus microarray to identify genes mis-expressed in mid-blastula stage runt-1 morphants. This analysis showed that loss of Runx function perturbs the expression of multiple genes involved in cell division, including the pro-growth and survival kinase Akt (PKB), which is significantly underexpressed in runt-1 morphants. Further genomic analysis revealed that Akt is encoded by two genes in the S. purpuratus genome, akt-1 and akt-2, both of which contain numerous canonical Runx target sequences. The transcripts of both genes accumulate several fold during blastula stage, contingent on runt-1 expression. Inhibiting Akt expression or activity causes blastula stage cell cycle arrest, whereas overexpression of akt-1 mRNA rescues cell proliferation in runt-1 morphants. These results indicate that post-cleavage stage cell division requires Runx-dependent expression of akt.

  12. Divergence to apoptosis from ROS induced cell cycle arrest: Effect of cadmium

    International Nuclear Information System (INIS)

    Recently, the role of cadmium (Cd) in immunosupression has gained importance. Nevertheless, the signaling pathways underlying cadmium-induced immune cell death remains largely unclear. In accordance to our previous in vivo report, and to evaluate the further details of the mechanism, we have investigated the effects of cadmium (CdCl2, H2O) on cell cycle regulation and apoptosis in splenocytes in vitro. Our results have revealed that reactive oxygen species (ROS) and p21 are involved in cell cycle arrest in a p53 independent manner but late hour apoptotic response was accompanied by the p53 up-regulation, loss of mitochondrial transmembrane potential (MTP), down-regulation of Bcl-xl, activation of caspase-3 and release of cytochrome c (Cyt c). However, pifithrin alfa (PFT-α), an inhibitor of p53, fails to rescue the cells from the cadmium-induced cell cycle arrest but prevents Bcl-xl down-regulation and loss of Δψm, which indicates that there is an involvement of p53 in apoptosis. In contrast, treatment with N-acetyl cysteine (NAC) can prevent cell cycle arrest and p21 up-regulation at early hours. Although it is clear that, NAC has no effect on apoptosis, p53 expression and MPT changes at late stage events. Taken together, we have demonstrated that cadmium promotes ROS generation, which potently initiates the cell cycle arrest at early hours and finally induces p53-dependent apoptosis at later part of the event.

  13. Staphylococcal Enterotoxin O Exhibits Cell Cycle Modulating Activity

    Science.gov (United States)

    Hodille, Elisabeth; Alekseeva, Ludmila; Berkova, Nadia; Serrier, Asma; Badiou, Cedric; Gilquin, Benoit; Brun, Virginie; Vandenesch, François; Terman, David S.; Lina, Gerard

    2016-01-01

    Maintenance of an intact epithelial barrier constitutes a pivotal defense mechanism against infections. Staphylococcus aureus is a versatile pathogen that produces multiple factors including exotoxins that promote tissue alterations. The aim of the present study is to investigate the cytopathic effect of staphylococcal exotoxins SEA, SEG, SEI, SElM, SElN and SElO on the cell cycle of various human cell lines. Among all tested exotoxins only SEIO inhibited the proliferation of a broad panel of human tumor cell lines in vitro. Evaluation of a LDH release and a DNA fragmentation of host cells exposed to SEIO revealed that the toxin does not induce necrosis or apoptosis. Analysis of the DNA content of tumor cells synchronized by serum starvation after exposure to SEIO showed G0/G1 cell cycle delay. The cell cycle modulating feature of SEIO was confirmed by the flow cytometry analysis of synchronized cells exposed to supernatants of isogenic S. aureus strains wherein only supernatant of the SElO producing strain induced G0/G1 phase delay. The results of yeast-two-hybrid analysis indicated that SEIO’s potential partner is cullin-3, involved in the transition from G1 to S phase. In conclusion, we provide evidence that SEIO inhibits cell proliferation without inducing cell death, by delaying host cell entry into the G0/G1 phase of the cell cycle. We speculate that this unique cell cycle modulating feature allows SEIO producing bacteria to gain advantage by arresting the cell cycle of target cells as part of a broader invasive strategy. PMID:27148168

  14. Dual Pressure versus Hybrid Recuperation in an Integrated Solid Oxide Fuel Cell Cycle – Steam Cycle

    DEFF Research Database (Denmark)

    Rokni, Masoud

    2014-01-01

    steam in a HRSG (heat recovery steam generator). The bottoming steam cycle was modeled with two configurations: (1) a simple single pressure level and (2) a dual pressure level with both a reheat and a pre-heater. The SOFC stacks in the present SOFC-ST hybrid cycles were not pressurized. The dual......A SOFC (solid oxide fuel cell) cycle running on natural gas was integrated with a ST (steam turbine) cycle. The fuel is desulfurized and pre-reformed before entering the SOFC. A burner was used to combust the remaining fuel after the SOFC stacks. The off-gases from the burner were used to produce...... pressure configuration steam cycle combined with SOFC cycle (SOFC-ST) was new and has not been studied previously. In each of the configuration, a hybrid recuperator was used to recovery the remaining energy of the off-gases after the HRSG. Thus, four different plants system setups were compared to each...

  15. Involvement of insulin in early development of mouse one-cell stage embryos

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Recent studies have suggested that growth factors and hormones play important roles in cell prolif-eration and differentiation during early embryonic development. In the present study, we examined the expression and localization of insulin in the mouse oocytes and one-cell stage embryos by quantitative ELISA, RT-PCR, Western blot and immunofluorescence. In the mouse oocytes and one-cell stage em-bryos, expression of insulin was uniformly distributed in the cytoplasm. We also examined the expres-sion, activity and localization of mTOR (mammalian target of rapamycin) and p70S6K. The expression of mTOR and p70S6K was not significantly different at the cell cycle of mouse one-cell stage embryos. mTOR and S6K were distributed evenly in the cytoplasm at G1, G2 and M phase phase, but at S phase, the distribution of mTOR and S6K was around the pronucleus. At different phases, the activity of mTOR fluctuated. We also used the PI3K specific inhibitor-Wortmannin to investigate the cleavage rate of eggs. The result showed that the rate obviously decreased. When the mTOR specific inhibitor Rapa-mycin was used, the first mitotic division of the mouse one-cell stage embryo was delayed. These re-sults suggested that insulin was expressed both in mouse oocytes and one-cell stage embryos, and may play functional roles in regulation of mouse early embryogenesis by activating the signal pathway of PI3K/PKB/mTOR/S6K.

  16. A revision of the Dictyostelium discoideum cell cycle.

    Science.gov (United States)

    Weijer, C J; Duschl, G; David, C N

    1984-08-01

    We have investigated the Dictyostelium discoideum cell cycle using fluorometric determinations of cellular and nuclear DNA contents in exponentially growing cultures and in synchronized cultures. Almost all cells are in G2 during both growth and development. There is no G1 period, S phase is less than 0.5 h, and G2 has an average length of 6.5 h in axenically grown cells. Mitochondrial DNA, which constitutes about half of the total DNA, is replicated throughout the cell cycle. There is no difference in the nuclear DNA contents of axenically grown and bacterially grown cells. Thus the long cell cycle in axenically grown cells is due to a lengthening of the G2 phase. PMID:6389576

  17. Cell-cycle inhibition by Helicobacter pylori L-asparaginase.

    Directory of Open Access Journals (Sweden)

    Claudia Scotti

    Full Text Available Helicobacter pylori (H. pylori is a major human pathogen causing chronic gastritis, peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. One of the mechanisms whereby it induces damage depends on its interference with proliferation of host tissues. We here describe the discovery of a novel bacterial factor able to inhibit the cell-cycle of exposed cells, both of gastric and non-gastric origin. An integrated approach was adopted to isolate and characterise the molecule from the bacterial culture filtrate produced in a protein-free medium: size-exclusion chromatography, non-reducing gel electrophoresis, mass spectrometry, mutant analysis, recombinant protein expression and enzymatic assays. L-asparaginase was identified as the factor responsible for cell-cycle inhibition of fibroblasts and gastric cell lines. Its effect on cell-cycle was confirmed by inhibitors, a knockout strain and the action of recombinant L-asparaginase on cell lines. Interference with cell-cycle in vitro depended on cell genotype and was related to the expression levels of the concurrent enzyme asparagine synthetase. Bacterial subcellular distribution of L-asparaginase was also analysed along with its immunogenicity. H. pylori L-asparaginase is a novel antigen that functions as a cell-cycle inhibitor of fibroblasts and gastric cell lines. We give evidence supporting a role in the pathogenesis of H. pylori-related diseases and discuss its potential diagnostic application.

  18. Studies on regulation of the cell cycle in fission yeast.

    Directory of Open Access Journals (Sweden)

    Miroslava Požgajová

    2015-05-01

    Full Text Available All living organisms including plants and animals are composed of millions of cells. These cells perform different functions for the organism although they possess the same chromosomes and carry the same genetic information. Thus, to be able to understand multicellular organism we need to understand the life cycle of individual cells from which the organism comprises. The cell cycle is the life cycle of a single cell in the plant or animal body. It involves series of events in which components of the cell doubles and afterwards equally segregate into daughter cells. Such process ensures growth of the organism, and specialized reductional cell division which leads to production of gamets, assures sexual reproduction. Cell cycle is divided in the G1, S, G2 and M phase. Two gap-phases (G1 and G2 separate S phase (or synthesis and M phase which stays either for mitosis or meiosis. Essential for normal life progression and reproduction is correct chromosome segregation during mitosis and meiosis. Defects in the division program lead to aneuploidy, which in turn leads to birth defects, miscarriages or cancer. Even thou, researchers invented much about the regulation of the cell cycle, there is still long way to understand the complexity of the regulatory machineries that ensure proper segregation of chromosomes. In this paper we would like to describe techniques and materials we use for our studies on chromosome segregation in the model organism Schizosaccharomyces pombe.

  19. Differential expression of glycosomal and mitochondrial proteins in the two major life-cycle stages of Trypanosoma brucei.

    Science.gov (United States)

    Vertommen, Didier; Van Roy, Joris; Szikora, Jean-Pierre; Rider, Mark H; Michels, Paul A M; Opperdoes, Fred R

    2008-04-01

    Label-free semi-quantitative differential three-dimensional liquid chromatography coupled to mass spectrometry (3D-LC-MS/MS) was used to compare the glycosomal and mitochondrial proteomes of the bloodstream- and insect-form of Trypanosoma brucei. The abundance of glycosomal marker proteins identified in the two life-cycle stages corresponded well with the relative importance of biochemical pathways present in the glycosomes of the two stages and the peptide spectral count ratios of selected enzymes were in good agreement with published data about their enzymatic specific activities. This approach proved extremely useful for the generation of large scale proteomics data for the comparison of different life-cycle stages. Several proteins involved in oxidative stress protection, sugar-nucleotide synthesis, purine salvage, nucleotide-monophosphate formation and purine-nucleotide cycle were identified as glycosomal proteins. PMID:18242729

  20. Thermodynamic Analysis of Double-Stage Compression Transcritical CO2 Refrigeration Cycles with an Expander

    OpenAIRE

    Zhenying Zhang; Lirui Tong; Xingguo Wang

    2015-01-01

    Four different double-compression CO2 transcritical refrigeration cycles are studied: double-compression external intercooler cycle (DCEI), double-compression external intercooler cycle with an expander (DCEIE), double-compression flash intercooler cycle (DCFI), double-compression flash intercooler cycle with an expander (DCFIE). The results showed that the optimum gas cooler pressure and optimum intermediate pressure of the flash intercooler cycles are lower than that of the external interco...

  1. The Architectural Organization of Human Stem Cell Cycle Regulatory Machinery

    OpenAIRE

    Stein, Gary S.; Stein, Janet L.; van Wijnen, Andre J.; Lian, Jane B.; Montecino, Martin; Medina, Ricardo(Instituto de Matemática e Computação, Universidade Federal de Itajubá, Itajubá, Minas Gerais, Brazil); Kapinas, Kristie; Ghule, Prachi; Grandy, Rodrigo; Zaidi, Sayyed K.; Becker, Klaus A.

    2012-01-01

    Two striking features of human embryonic stem cells that support biological activity are an abbreviated cell cycle and reduced complexity to nuclear organization. The potential implications for rapid proliferation of human embryonic stem cells within the context of sustaining pluripotency, suppressing phenotypic gene expression and linkage to simplicity in the architectural compartmentalization of regulatory machinery in nuclear microenvironments is explored. Characterization of the molecular...

  2. Molecular signatures of cell cycle transcripts in the pathogenesis of Glial tumors

    Directory of Open Access Journals (Sweden)

    Bhattacharya Rabindra

    2004-01-01

    Full Text Available Abstract Background Astrocytic brain tumors are among the most lethal and morbid tumors of adults, often occurring during the prime of life. These tumors form an interesting group of cancer to understand the molecular mechanism of pathogenesis. Histological grading of Astrocytoma based on WHO classification does not provide complete information on the proliferation potential and biological behavior of the tumors. It is known that cancer results from the disruption of the orderly regulated cycle of replication and division. In the present study, we made an attempt to identify the cell cycle signatures and their involvement in the clinical aggressiveness of gliomas. Methods The variation in expression of various cell cycle genes was studied in different stages of glial tumor progression (low and high grades, and the results were compared with their corresponding expression levels in the normal brain tissue. Macroarray analysis was used for the purpose. Results Macroarray analysis of 114 cell cycle genes in different grades of glioma indicated differential expression pattern in 34% of the gene transcripts, when compared to the normal tissue. Majority of the transcripts belong to the intracellular kinase networks, cell cycle regulating kinases, transcription factors and transcription activators. Conclusion Based on the observation in the expression pattern in low grade and high grade gliomas, it can be suggested that the upregulation of cell cycle activators are seen as an early event in glioma; however, in malignancy it is not the cell cycle activators alone, which are involved in tumorigenesis. Understanding the molecular details of cell cycle regulation and checkpoint abnormalities in cancer could offer an insight into potential therapeutic strategies.

  3. Thermodynamic Analysis of Double-Stage Compression Transcritical CO2 Refrigeration Cycles with an Expander

    Directory of Open Access Journals (Sweden)

    Zhenying Zhang

    2015-04-01

    Full Text Available Four different double-compression CO2 transcritical refrigeration cycles are studied: double-compression external intercooler cycle (DCEI, double-compression external intercooler cycle with an expander (DCEIE, double-compression flash intercooler cycle (DCFI, double-compression flash intercooler cycle with an expander (DCFIE. The results showed that the optimum gas cooler pressure and optimum intermediate pressure of the flash intercooler cycles are lower than that of the external intercooler cycle. The use of an expander in the DCEI cycle leads to a decrease of the optimum gas cooler pressure and little variation of the optimum intermediate pressure. However, the replacement of the throttle valve with an expander in the DCFI cycle results in little variation of the optimal gas cooler pressure and an increase of the optimum intermediate pressure. The DCFI cycle outperforms the DCEI cycle under all the chosen operating conditions. The DCEIE cycle outperforms the DCFIE cycle when the evaporating temperature exceeds 0 °C or the gas cooler outlet temperature surpasses 35 °C. When the gas cooler exit temperature varies from 32 °C to 48 °C, the DCEI cycle, DCEIE cycle, DCFI cycle and DCFIE cycle yield averaged 4.6%, 29.2%, 12.9% and 22.3% COP improvement, respectively, over the basic cycle.

  4. Quantification of mast cells in different stages of periodontal disease

    Directory of Open Access Journals (Sweden)

    Marjanović Dragan

    2016-01-01

    Full Text Available Background/Aim. Mast cells are mononuclear cells originating from bone marrow. They produce various biologically active substances, which allow them to actively participate in immune and inflammatory processes associated with periodontal disease. The study focused on distribution and density of mast cells in healthy gingiva as well as in different stages of periodontal disease. Methods. The material used for this purpose was gingival biopsies taken from 96 patients classified into 4 groups: healthy gingiva, gingivitis, initial and severe periodontal disease. Toluidine blue staining according to Spicer was utilized for identifying mast cells. Results. Basing on our study, the density of mast cells in the gingival tissue increases with the progression of the infection, which means they are more numerous in gingivitis compared to healthy gingiva, as well as in periodontal disease compared to gingivitis. Conclusion. Increase in the number of mast cells in the infected gingiva can be correlated with an increased influx of inflammatory cells from blood circulation into the gingival stroma, as well as with the collagen lysis, since these cells produce substances with collagenolytic potential. Based on the distribution of mast cells, it could be concluded that in the evolution of periodontal disease there are significant dynamic alterations in migration and localization of these cells.

  5. First Law Analysis of a Two-stage Ejector-vapor Compression Refrigeration Cycle working with R404A

    Directory of Open Access Journals (Sweden)

    Feiza Memet

    2011-10-01

    Full Text Available The traditional two-stage vapor compression refrigeration cycle might be replaced by a two-stage ejector-vapor compression refrigeration cycle if it is aimed the decrease of irreversibility during expansion. In this respect, the expansion valve is changed with an ejector. The performance improvement is searched in the case of choosing R404A as a refrigerant. Using the ejector as an expansion device ensures a higher value for COP compared to the traditional case. On the basis of the ejector approach it possible to identify the highest COP value for a given condensation temperature, when the evaporation temperature varies.

  6. Large scale spontaneous synchronization of cell cycles in amoebae

    Science.gov (United States)

    Segota, Igor; Boulet, Laurent; Franck, Carl

    2014-03-01

    Unicellular eukaryotic amoebae Dictyostelium discoideum are generally believed to grow in their vegetative state as single cells until starvation, when their collective aspect emerges and they differentiate to form a multicellular slime mold. While major efforts continue to be aimed at their starvation-induced social aspect, our understanding of population dynamics and cell cycle in the vegetative growth phase has remained incomplete. We show that substrate-growtn cell populations spontaneously synchronize their cell cycles within several hours. These collective population-wide cell cycle oscillations span millimeter length scales and can be completely suppressed by washing away putative cell-secreted signals, implying signaling by means of a diffusible growth factor or mitogen. These observations give strong evidence for collective proliferation behavior in the vegetative state and provide opportunities for synchronization theories beyond classic Kuramoto models.

  7. Effects of canine serum collected from dogs at different estrous cycle stages on in vitro nuclear maturation of canine oocytes.

    Science.gov (United States)

    Oh, Hyun Ju; Fibrianto, Yuda Heru; Kim, Min Kyu; Jang, Goo; Hossein, M Shamim; Kim, Hye Jin; Kang, Sung Keun; Lee, Byeong Chun; Hwang, Woo Suk

    2005-08-01

    Canine oocytes are ovulated at prophase of the first meiotic division and undergo maturation in the distal part of the oviduct for at least 48-72 h. Because of these differences from other domestic mammals, the efficiency of in vitro maturation (IVM) of canine oocyte is very low. The present study was conducted to evaluate the effects of canine serum on IVM of canine oocytes recovered from ovaries in various reproductive states (follicular, luteal or anestrous stages). Oocytes were recovered by mincing ovaries from bitches presented for ovariohysterectomy at various stages of the estrous cycle. Heat-inactivated canine serum was prepared with blood taken from dogs at the anestrous, estrous or diestrous stage of the estrous cycle as determined by progesterone concentration and vaginal cytology. Oocytes were cultured for 72 h in tissue culture medium (TCM)-199 supplemented with 10% canine anestrous, estrous or diestrous serum or fetal bovine serum (FBS) (experiment 1), or supplemented with 0 (control), 5%, 10% or 20% canine estrous serum (experiment 2). In experiment 1, IVM of oocytes collected at the follicular stage of the estrous cycle to metaphase II (MII) stage was higher (p < 0.05) with canine estrous serum (14.2%) than with canine anestrous (5.2%) or diestrous serum (6.3%), FBS (2.2%) or in the control (2.2%). In experiment 2, oocytes collected at the follicular stage of the estrous cycle cultured in TCM-199 with 10% canine estrous serum showed a higher maturation rate to MII stage (13.5%, p < 0.05) compared with those cultured with 5% (1.3% MII) or 20% canine estrous serum (5.1% MII) or the control (2.7% MII). In conclusion, our results demonstrate that supplementing culture medium with 10% canine estrous serum improves IVM of canine follicular stage oocytes. PMID:16261767

  8. Cell cycle deregulation by methyl isocyanate: Implications in liver carcinogenesis.

    Science.gov (United States)

    Panwar, Hariom; Raghuram, Gorantla V; Jain, Deepika; Ahirwar, Alok K; Khan, Saba; Jain, Subodh K; Pathak, Neelam; Banerjee, Smita; Maudar, Kewal K; Mishra, Pradyumna K

    2014-03-01

    Liver is often exposed to plethora of chemical toxins. Owing to its profound physiological role and central function in metabolism and homeostasis, pertinent succession of cell cycle in liver epithelial cells is of prime importance to maintain cellular proliferation. Although recent evidence has displayed a strong association between exposures to methyl isocyanate (MIC), one of the most toxic isocyanates, and neoplastic transformation, molecular characterization of the longitudinal effects of MIC on cell cycle regulation has never been performed. Here, we sequentially delineated the status of different proteins arbitrating the deregulation of cell cycle in liver epithelial cells treated with MIC. Our data reaffirms the oncogenic capability of MIC with elevated DNA damage response proteins pATM and γ-H2AX, deregulation of DNA damage check point genes CHK1 and CHK2, altered expression of p53 and p21 proteins involved in cell cycle arrest with perturbation in GADD-45 expression in the treated cells. Further, alterations in cyclin A, cyclin E, CDK2 levels along with overexpression of mitotic spindle checkpoints proteins Aurora A/B, centrosomal pericentrin protein, chromosomal aberrations, and loss of Pot1a was observed. Thus, MIC impacts key proteins involved in cell cycle regulation to trigger genomic instability as a possible mechanism of developmental basis of liver carcinogenesis. PMID:22223508

  9. P27 in cell cycle control and cancer

    DEFF Research Database (Denmark)

    Møller, Michael Boe

    In order to survive, cells need tight control of cell cycle progression. The control mechanisms are often lost in human cancer cells. The cell cycle is driven forward by cyclin-dependent kinases (CDKs). The CDK inhibitors (CKIs) are important regulators of the CDKs. As the name implies, CKIs were...... distinct NHL entities however, shortened survival seems to correlate with high expression of p27. For definitive assessment of the role played by p27 in lymphomagenesis, and the prognostic value of p27 in these tumors, further studies of distinct NHL entities are needed. This review addresses the function...

  10. Thermally regenerative hydrogen/oxygen fuel cell power cycles

    Science.gov (United States)

    Morehouse, J. H.

    1986-01-01

    Two innovative thermodynamic power cycles are analytically examined for future engineering feasibility. The power cycles use a hydrogen-oxygen fuel cell for electrical energy production and use the thermal dissociation of water for regeneration of the hydrogen and oxygen. The TDS (thermal dissociation system) uses a thermal energy input at over 2000 K to thermally dissociate the water. The other cycle, the HTE (high temperature electrolyzer) system, dissociates the water using an electrolyzer operating at high temperature (1300 K) which receives its electrical energy from the fuel cell. The primary advantages of these cycles is that they are basically a no moving parts system, thus having the potential for long life and high reliability, and they have the potential for high thermal efficiency. Both cycles are shown to be classical heat engines with ideal efficiency close to Carnot cycle efficiency. The feasibility of constructing actual cycles is investigated by examining process irreversibilities and device efficiencies for the two types of cycles. The results show that while the processes and devices of the 2000 K TDS exceed current technology limits, the high temperature electrolyzer system appears to be a state-of-the-art technology development. The requirements for very high electrolyzer and fuel cell efficiencies are seen as determining the feasbility of the HTE system, and these high efficiency devices are currently being developed. It is concluded that a proof-of-concept HTE system experiment can and should be conducted.

  11. Small-scale hydrogen liquefaction with a two-stage Gifford-McMahon cycle refrigerator

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Akihiro; Maeda, Tetsuhiko; Ito, Hiroshi [National Institute of Advanced Industrial Science and Technology, Energy Technology Research Institute, 1-2-1 Namiki, Tsukuba East, Tsukuba, Ibaraki 305-8564 (Japan); Masuda, Masao; Kawakami, Yoshiaki; Kato, Atsushi [Takasago Thermal Engineering Co., Ltd., Research and Development Center, 3150 Iiyama Atsugi City, Kanagawa 243-0213 (Japan); Tange, Manabu [Shibaura Institute of Technology, Department of Mechanical Engineering, 3-7-5 Toyosu Koto-ku, Tokyo 135-8548 (Japan); Takahashi, Toru [University of Tsukuba, Department of Engineering Mechanics and Energy, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573 (Japan); Matsuo, Masahiro [JECC Torisha Co., Ltd., 2-8-52 Yoshinodai, Kawagoe, Saitama 350-0833 (Japan)

    2010-09-15

    We manufactured a small-scale hydrogen liquefier with a two-stage 10 K Gifford-McMahon cycle (GM) refrigerator. It had a hydrogen tank with the volume of 30 L that was surrounded by a radiation shield. This liquefier continuously liquefied gaseous hydrogen with the volumetric flow rate of 12.1 NL/min. It corresponds to the liquefaction rate of 19.9 L/day for liquid hydrogen. We proposed a simple estimation method for the liquefaction rate and confirmed that the estimation method well explained the experimental result. To evaluate the estimation method, we applied the estimation method to other liquefiers. In case of a liquefier with the GM refrigerator, we confirmed the estimation method was available for predicting the liquefaction rate. However, in case of a liquefier with the pulse tube refrigerator, the results of the estimation indicated small values as compared with the experimental data. We discuss the details about the estimation method of the liquefaction rate for the small-scale liquefiers. (author)

  12. Diagnostic importance of CT in early stage renal cell carcinoma

    International Nuclear Information System (INIS)

    Our experience of finding a small renal cell carcinoma by CT suggested the diagnostic importance of CT in the early stage of the tumor. The patient was a forty-year-old woman who had suffered several times from pyelonephritis. She consulted us for detailed examination. IVP showed only slight deformity like a calceal diverticulum at the upper. pole of the left kidney. Ultrasonic tomography failed to expose the region. Enhanced CT revealed a small space occupying lesion like a simple renal cyst at the region, though plain CT revealed no abnormal findings. From the comparison of these two CT, she was diagnosed to have renal cell carcinoma which was confirmed by renal arteriography. Subsequently, transabdominal left nephrectomy was performed. Pathological diagnosis was renal cell carcinoma (clear cell type). The tumor size was very small, 1.5 cm in diameter. Comparison of plain and enhanced CT were considered important to diagnose a small tumor, and CT is now the most useful examination to detect early stage renal cell carcinoma. (author)

  13. The timing of T cell priming and cycling

    Directory of Open Access Journals (Sweden)

    Reinhard eObst

    2015-11-01

    Full Text Available The proliferation of specific lymphocytes is the central tenet of the clonal selection paradigm. Antigen recognition by T cells triggers a series of events that produces expanded clones of differentiated effector cells. TCR signaling events are detectable within seconds and minutes and are likely to continue for hours and days in vivo. Here, I review the work done on the importance of TCR signals in the later part of the expansion phase of the primary T cell response, primarily regarding the regulation of the cell cycle in CD4+ and CD8+ cells. The results suggest a degree of programming by early signals for effector differentiation, particularly in the CD8+ T cell compartment, with optimal expansion supported by persistent antigen presentation later on. Differences to CD4+ T cell expansion and new avenues towards a molecular understanding of cell cycle regulation in lymphocytes are discussed.

  14. Targeting the cancer cell cycle by cold atmospheric plasma

    Science.gov (United States)

    Volotskova, O.; Hawley, T. S.; Stepp, M. A.; Keidar, M.

    2012-09-01

    Cold atmospheric plasma (CAP), a technology based on quasi-neutral ionized gas at low temperatures, is currently being evaluated as a new highly selective alternative addition to existing cancer therapies. Here, we present a first attempt to identify the mechanism of CAP action. CAP induced a robust ~2-fold G2/M increase in two different types of cancer cells with different degrees of tumorigenicity. We hypothesize that the increased sensitivity of cancer cells to CAP treatment is caused by differences in the distribution of cancer cells and normal cells within the cell cycle. The expression of γH2A.X (pSer139), an oxidative stress reporter indicating S-phase damage, is enhanced specifically within CAP treated cells in the S phase of the cell cycle. Together with a significant decrease in EdU-incorporation after CAP, these data suggest that tumorigenic cancer cells are more susceptible to CAP treatment.

  15. Development of a Two-Stage Microalgae Dewatering Process - A Life Cycle Assessment Approach.

    Science.gov (United States)

    Soomro, Rizwan R; Ndikubwimana, Theoneste; Zeng, Xianhai; Lu, Yinghua; Lin, Lu; Danquah, Michael K

    2016-01-01

    Even though microalgal biomass is leading the third generation biofuel research, significant effort is required to establish an economically viable commercial-scale microalgal biofuel production system. Whilst a significant amount of work has been reported on large-scale cultivation of microalgae using photo-bioreactors and pond systems, research focus on establishing high performance downstream dewatering operations for large-scale processing under optimal economy is limited. The enormous amount of energy and associated cost required for dewatering large-volume microalgal cultures has been the primary hindrance to the development of the needed biomass quantity for industrial-scale microalgal biofuels production. The extremely dilute nature of large-volume microalgal suspension and the small size of microalgae cells in suspension create a significant processing cost during dewatering and this has raised major concerns towards the economic success of commercial-scale microalgal biofuel production as an alternative to conventional petroleum fuels. This article reports an effective framework to assess the performance of different dewatering technologies as the basis to establish an effective two-stage dewatering system. Bioflocculation coupled with tangential flow filtration (TFF) emerged a promising technique with total energy input of 0.041 kWh, 0.05 kg CO2 emissions and a cost of $ 0.0043 for producing 1 kg of microalgae biomass. A streamlined process for operational analysis of two-stage microalgae dewatering technique, encompassing energy input, carbon dioxide emission, and process cost, is presented. PMID:26904075

  16. Development of a Two-Stage Microalgae Dewatering Process – A Life Cycle Assessment Approach

    Science.gov (United States)

    Soomro, Rizwan R.; Zeng, Xianhai; Lu, Yinghua; Lin, Lu; Danquah, Michael K.

    2016-01-01

    Even though microalgal biomass is leading the third generation biofuel research, significant effort is required to establish an economically viable commercial-scale microalgal biofuel production system. Whilst a significant amount of work has been reported on large-scale cultivation of microalgae using photo-bioreactors and pond systems, research focus on establishing high performance downstream dewatering operations for large-scale processing under optimal economy is limited. The enormous amount of energy and associated cost required for dewatering large-volume microalgal cultures has been the primary hindrance to the development of the needed biomass quantity for industrial-scale microalgal biofuels production. The extremely dilute nature of large-volume microalgal suspension and the small size of microalgae cells in suspension create a significant processing cost during dewatering and this has raised major concerns towards the economic success of commercial-scale microalgal biofuel production as an alternative to conventional petroleum fuels. This article reports an effective framework to assess the performance of different dewatering technologies as the basis to establish an effective two-stage dewatering system. Bioflocculation coupled with tangential flow filtration (TFF) emerged a promising technique with total energy input of 0.041 kWh, 0.05 kg CO2 emissions and a cost of $ 0.0043 for producing 1 kg of microalgae biomass. A streamlined process for operational analysis of two-stage microalgae dewatering technique, encompassing energy input, carbon dioxide emission, and process cost, is presented. PMID:26904075

  17. Stage-by-Stage and Parallel Flow Path Compressor Modeling for a Variable Cycle Engine, NASA Advanced Air Vehicles Program - Commercial Supersonic Technology Project - AeroServoElasticity

    Science.gov (United States)

    Kopasakis, George; Connolly, Joseph W.; Cheng, Larry

    2015-01-01

    This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

  18. Erlotinib Hydrochloride and Radiation Therapy in Stage III-IV Squamous Cell Cancer of the Head and Neck

    Science.gov (United States)

    2012-10-30

    Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity

  19. Cell cycle effects for radiosensitivity after heavy ion exposure

    International Nuclear Information System (INIS)

    In order to study the relative contribution of the two major DNA double-strand break (DSB) repair pathways, non-homologous end-joining (NHEJ) and homologous recombinational repair (HRR), to the repair of DSBs and non-DSB clustered DNA damage induced by high linear energy transfer (LET) ionizing radiation through the cell cycle, we exposed wild type (WT), NHEJ-deficient, and HRR-deficient Chinese hamster ovary (CHO) cells synchronized by mitotic shake-off to accelerated heavy ions and X-rays. The cell cycle-dependent variation in survival observed in WT cells after X-irradiation was not observed after exposure to 500 MeV/amu iron ions. Non-homologous end joining (NHEJ) and homologous recombinational repair (HRR)-defective cells showed different patterns of cell cycle-dependent radiosensitivity after X-irradiation compared to WT cells, that were likewise significantly attenuated after iron ion exposures. Higher relative biological effectiveness for several other accelerated heavy ions (C, Ne, Si, Ar) of differing LETs was observed for cells exposed in S phase compared to cells exposed in G1. We also observed that HRR deficiency, unlike NHEJ deficiency, did not affect the progression of irradiated G2 cells into mitosis, thus contributing to increased cell killing observed in G2-phase HRR-deficient cells. The HRR-deficient cells showed significantly increased levels of chromatid-type aberrations that correlated with their cell cycle pattern of survival after both X- and iron ion irradiation. Our results suggest that high LET radiation produces not only complex DSBs but also complex non-DSB clustered lesions that specifically require the HRR-mediated repair of these lesions if encountered during DNA replication. In this year, we focused on Fanconi Anemia DNA repair pathway. Only FancA mutant cells showed hypersensitivity to high LET ionizing radiation among other FancC, FancD1, FancD2, and FancG mutant cells. (author)

  20. Cell Cycle Inhibition without Disruption of Neurogenesis Is a Strategy for Treatment of Aberrant Cell Cycle Diseases: An Update

    OpenAIRE

    Da-Zhi Liu; Ander, Bradley P.

    2012-01-01

    Since publishing our earlier report describing a strategy for the treatment of central nervous system (CNS) diseases by inhibiting the cell cycle and without disrupting neurogenesis (Liu et al. 2010), we now update and extend this strategy to applications in the treatment of cancers as well. Here, we put forth the concept of “aberrant cell cycle diseases” to include both cancer and CNS diseases, the two unrelated disease types on the surface, by focusing on a common mechanism in each aberr...

  1. Cell cycle synchronization of embryonic stem cells: Effect of serum deprivation on the differentiation of embryonic bodies in vitro

    International Nuclear Information System (INIS)

    Research on stem-cell transplantation has indicated that the success of transplantation largely depends on synchronizing donor cells into the G0/G1 phase. In this study, we investigated the profile of embryonic stem (ES) cell synchronization and its effect on the formation of embryonic bodies (EBs) using cell culture with serum deprivation. The D3 cell line of ES cells was used, and parameters such as cell proliferation and activity, EB formation, and expression of stage-specific embryonic antigen-1 and Oct-4 were investigated. Results showed that the percentage of G0/G1 stage in serum deprivation culture is significantly higher than that in culture with serum supplementation. Synchronized ES cells can reenter the normal cell cycle successfully after serum supply. EBs formed from synchronized ES cells have higher totipotency capability to differentiate into functional neuronal cells than EBs formed from unsynchronized ES cells. Our study provides a method for ES treatment before cell transplantation that possibly helps to decrease the rate of cell death after transplantation

  2. Low-density microarray analysis of TGFβ1-dependent cell cycle regulation in human breast adenocarcinoma MCF7 cell line

    Directory of Open Access Journals (Sweden)

    Dubrovska A. M.

    2014-03-01

    Full Text Available Transforming growth factor β1 (TGFβ1 is a growth regulator that has antiproliferative effects on a range of epithelial cells at the early stages and promoting tumorigenesis at the later stages of cancer progression. The molecular mechanisms of a duel role of TGFβ1 in tumor growth regulation remain poorly understood. Aim. To analyze the TGFβ1-dependent cell cycle regulation of tumorigenic breast epithelial cells. Methods. Our present study was designed to examine the regulatory effect of TGFβ1 on the expression of a panel of 96 genes which are known to be critically involved in cell cycle regulation. GEArray Q series Human Cell Cycle Gene Array was applied to profile the gene expression changes in MCF7 human breast adenocarcinoma cell line treated with TGFβ1. Results. The gene expression array data enabled us to reveal the molecular regulators that might connect TGFβ1 signaling to the promoting of the tumor growth, e. g. retinoblastoma protein (pRB1, check-point kinase 2 (Chk2, breast cancer 1, early onset (BRCA1, DNA damage checkpoint protein RAD9, cyclin-dependent kinase 2 (CDK2, cyclin D1 (CCND1. Conclusions. The uncovering of the key signaling modules involved in TGFβ1- dependent signaling might provide an insight into the mechanisms of TGFβ1-dependent tumor growth and can be beneficial for the development of novel therapeutic approaches.

  3. Creatine kinase in cell cycle regulation and cancer.

    Science.gov (United States)

    Yan, Yong-Bin

    2016-08-01

    The phosphocreatine-creatine kinase (CK) shuttle system is increasingly recognized as a fundamental mechanism for ATP homeostasis in both excitable and non-excitable cells. Many intracellular processes are ATP dependent. Cell division is a process requiring a rapid rate of energy turnover. Cell cycle regulation is also a key point to understanding the mechanisms underlying cancer progression. It has been known for about 40 years that aberrant CK levels are associated with various cancers and for over 30 years that CK is involved in mitosis regulation. However, the underlying molecular mechanisms have not been investigated sufficiently until recently. By maintaining ATP at sites of high-energy demand, CK can regulate cell cycle progression by affecting the intracellular energy status as well as by influencing signaling pathways that are essential to activate cell division and cytoskeleton reorganization. Aberrant CK levels may impair cell viability under normal or stressed conditions and induce cell death. The involvement of CK in cell cycle regulation and cellular energy metabolism makes it a potential diagnostic biomarker and therapeutic target in cancer. To understand the multiple physiological/pathological functions of CK, it is necessary to identify CK-binding partners and regulators including proteins, non-coding RNAs and participating endogenous small molecular weight chemical compounds. This review will focus on molecular mechanisms of CK in cell cycle regulation and cancer progression. It will also discuss the implications of recent mechanistic studies, the emerging problems and future challenges of the multifunctional enzyme CK. PMID:27020776

  4. Nanosecond pulsed electric fields and the cell cycle

    Science.gov (United States)

    Mahlke, Megan A.

    Exposure to nanosecond pulsed electrical fields (nsPEFs) can cause poration of external and internal cell membranes, DNA damage, and disassociation of cytoskeletal components, all of which are capable of disrupting a cell's ability to replicate. The phase of the cell cycle at the time of exposure is linked to differential sensitivities to nsPEFs across cell lines, as DNA structure, membrane elasticity, and cytoskeletal structure change dramatically during the cell cycle. Additionally, nsPEFs are capable of activating cell cycle checkpoints, which could lead to apoptosis or slow population growth. NsPEFs are emerging as a method for treating tumors via apoptotic induction; therefore, investigating the relevance of nsPEFs and the cell cycle could translate into improved efficacy in tumor treatment. Populations of Jurkat and Chinese Hamster Ovary (CHO) cells were examined post-exposure (10 ns pulse trains at 150kV/cm) by analysis of DNA content via propidium iodide staining and flow cytometric analysis at various time points (1, 6, and 12h post-exposure) to determine population distribution in cell cycle phases. Additionally, CHO and Jurkat cells were synchronized in G1/S and G2/M phases, pulsed, and analyzed to evaluate the role of cell cycle phase in survival of nsPEFs. CHO populations appeared similar to sham populations post-nsPEFs but exhibited arrest in the G1 phase at 6h after exposure. Jurkat cells exhibited increased cell death after nsPEFs compared to CHO cells but did not exhibit checkpoint arrest at any observed time point. The G1/S phase checkpoint is partially controlled by the action of p53; the lack of an active p53 response in Jurkat cells could contribute to their ability to pass this checkpoint and resist cell cycle arrest. Both cell lines exhibited increased sensitivity to nsPEFs in G2/M phase. Live imaging of CHO cells after nsPEF exposure supports the theory of G1/S phase arrest, as a reduced number of cells undergo mitosis within 24 h when

  5. Mitochondrial Regulation of Cell Cycle and Proliferation

    OpenAIRE

    Antico Arciuch, Valeria Gabriela; Elguero, María Eugenia; Poderoso, Juan José; Carreras, María Cecilia

    2012-01-01

    Eukaryotic mitochondria resulted from symbiotic incorporation of α-proteobacteria into ancient archaea species. During evolution, mitochondria lost most of the prokaryotic bacterial genes and only conserved a small fraction including those encoding 13 proteins of the respiratory chain. In this process, many functions were transferred to the host cells, but mitochondria gained a central role in the regulation of cell proliferation and apoptosis, and in the modulation of metabolism; accordingly...

  6. Energy Efficiency as a Factor of Engineering Product Competitiveness and its Formation on Product Economic Life Cycle Stages

    Directory of Open Access Journals (Sweden)

    Ivan V. Evstratov

    2011-11-01

    Full Text Available This article discusses the concept of energy efficiency of enterprises and engineering products. The author research how energy efficiency effect on engineering product competitiveness and how rate of enterprise and engineering product formation on stages of the economic product life cycle.

  7. Energy Efficiency as a Factor of Engineering Product Competitiveness and its Formation on Product Economic Life Cycle Stages

    OpenAIRE

    Ivan V. Evstratov

    2011-01-01

    This article discusses the concept of energy efficiency of enterprises and engineering products. The author research how energy efficiency effect on engineering product competitiveness and how rate of enterprise and engineering product formation on stages of the economic product life cycle.

  8. Personal Authority via Termination of the Intergenerational Hierarchical Boundary: A "New" Stage in the Family Life Cycle.

    Science.gov (United States)

    Williamson, Donald S.

    1981-01-01

    Proposes and describes a stage in the family life cycle which terminates the hierarchical boundary between the adult client and the older parents. Describes the process of redistribution of power that establishes a peer relationship between the first and second generations. (Author)

  9. The epigenetic regulation of cell cycle and chromatin dynamic by sirtuins

    OpenAIRE

    Martínez Redondo, Paloma

    2014-01-01

    Tesi realitzada a l'Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) The chromatin consists of a hierarchical and dynamical structure that is modulated during the different cell cycle stages in order to maintain genome integrity and preserve the genetic information coded in the DNA. The dynamic structure of the chromatin depends on the coordination of the different chromatin remodeling processes: histone modifications, chromatin remodeling enzymes/complexes, DNA methylation and chr...

  10. Toxoplasma gondii sequesters centromeres to a specific nuclear region throughout the cell cycle

    OpenAIRE

    Brooks, Carrie F; Francia, Maria E.; Gissot, Mathieu; Croken, Matthew M.; Kim, Kami; Striepen, Boris

    2011-01-01

    Members of the eukaryotic phylum Apicomplexa are the cause of important human diseases including malaria, toxoplasmosis, and cryptosporidiosis. These obligate intracellular parasites produce new invasive stages through a complex budding process. The budding cycle is remarkably flexible and can produce varied numbers of progeny to adapt to different host-cell niches. How this complex process is coordinated remains poorly understood. Using Toxoplasma gondii as a genetic model, we show that a ke...

  11. The cell cycle-regulated genes of Schizosaccharomyces pombe.

    Directory of Open Access Journals (Sweden)

    Anna Oliva

    2005-07-01

    Full Text Available Many genes are regulated as an innate part of the eukaryotic cell cycle, and a complex transcriptional network helps enable the cyclic behavior of dividing cells. This transcriptional network has been studied in Saccharomyces cerevisiae (budding yeast and elsewhere. To provide more perspective on these regulatory mechanisms, we have used microarrays to measure gene expression through the cell cycle of Schizosaccharomyces pombe (fission yeast. The 750 genes with the most significant oscillations were identified and analyzed. There were two broad waves of cell cycle transcription, one in early/mid G2 phase, and the other near the G2/M transition. The early/mid G2 wave included many genes involved in ribosome biogenesis, possibly explaining the cell cycle oscillation in protein synthesis in S. pombe. The G2/M wave included at least three distinctly regulated clusters of genes: one large cluster including mitosis, mitotic exit, and cell separation functions, one small cluster dedicated to DNA replication, and another small cluster dedicated to cytokinesis and division. S. pombe cell cycle genes have relatively long, complex promoters containing groups of multiple DNA sequence motifs, often of two, three, or more different kinds. Many of the genes, transcription factors, and regulatory mechanisms are conserved between S. pombe and S. cerevisiae. Finally, we found preliminary evidence for a nearly genome-wide oscillation in gene expression: 2,000 or more genes undergo slight oscillations in expression as a function of the cell cycle, although whether this is adaptive, or incidental to other events in the cell, such as chromatin condensation, we do not know.

  12. CycleBase.org - a comprehensive multi-organism online database of cell-cycle experiments

    DEFF Research Database (Denmark)

    Gauthier, Nicholas Paul; Larsen, Malene Erup; Wernersson, Rasmus;

    2007-01-01

    The past decade has seen the publication of a large number of cell-cycle microarray studies and many more are in the pipeline. However, data from these experiments are not easy to access, combine and evaluate. We have developed a centralized database with an easy-to-use interface, Cyclebase.......org, for viewing and downloading these data. The user interface facilitates searches for genes of interest as well as downloads of genome-wide results. Individual genes are displayed with graphs of expression profiles throughout the cell cycle from all available experiments. These expression profiles are...

  13. Cell cycle effects for radiosensitivity after heavy ion exposure

    International Nuclear Information System (INIS)

    In order to study the relative contribution of the two major DNA double-strand break (DSB) repair pathways, non-homologous end-joining (NHEJ) and homologous recombinational repair (HRR), to the repair of DSBs and non-DSB clustered DNA damage induced by high linear energy transfer (LET) ionizing radiation through the cell cycle, we exposed wild type (WT), NHEJ-deficient, and HRR-deficient Chinese hamster ovary (CHO) cells synchronized by mitotic shake-off to accelerated heavy ions and X-rays. The cell cycle-dependent variation in survival observed in WT cells after X-irradiation was not observed after exposure to 500 MeV/amu iron ions. Non-homologous end joining (NHEJ) and homologous recombinational repair (HRR)-defective cells showed different patterns of cell cycle-dependent radiosensitivity after X-irradiation compared to WT cells, that were likewise significantly attenuated after iron ion exposures. Higher relative biological effectiveness for several other accelerated heavy ions (C, Ne, Si, Ar) of differing LETs was observed for cells exposed in S phase compared to cells exposed in G1. We also observed that HRR deficiency, unlike NHEJ deficiency, did not affect the progression of irradiated G2 cells into mitosis, thus contributing to increased cell killing observed in G2-phase HRR-deficient cells. The HRR-deficient cells showed significantly increased levels of chromatid-type aberrations that correlated with their cell cycle pattern of survival after both X- and iron ion irradiation. Our results suggest that high LET radiation produces not only complex DSBs but also complex non-DSB clustered lesions that specifically require the HRR-mediated repair of these lesions if encountered during DNA replication. (author)

  14. Patterns of cell division revealed by transcriptional regulation of genes during the cell cycle in plants.

    OpenAIRE

    Fobert, P R; Coen, E S; Murphy, G. J.; Doonan, J H

    1994-01-01

    Transcripts from five cell cycle related genes accumulate in isolated cells dispersed throughout the actively dividing regions of plant meristems. We propose that this pattern reflects gene expression during particular phases of the cell division cycle. The high proportion of isolated cells suggests that synchrony between daughter cells is rapidly lost following mitosis. This is the first time that such a cell specific expression pattern has been described in a higher organism. Counterstainin...

  15. Cell cycle sibling rivalry: Cdc2 vs. Cdk2.

    Science.gov (United States)

    Kaldis, Philipp; Aleem, Eiman

    2005-11-01

    It has been long believed that the cyclin-dependent kinase 2 (Cdk2) binds to cyclin E or cyclin A and exclusively promotes the G1/S phase transition and that Cdc2/cyclin B complexes play a major role in mitosis. We now provide evidence that Cdc2 binds to cyclin E (in addition to cyclin A and B) and is able to promote the G1/S transition. This new concept indicates that both Cdk2 and/or Cdc2 can drive cells through G1/S phase in parallel. In this review we discuss the classic cell cycle model and how results from knockout mice provide new evidence that refute this model. We focus on the roles of Cdc2 and p27 in regulating the mammalian cell cycle and propose a new model for cell cycle regulation that accommodates these novel findings. PMID:16258277

  16. Using a GFP-gene fusion technique to study the cell cycle-dependent distribution of calmodulin in living cells

    Institute of Scientific and Technical Information of China (English)

    李朝军; 吕品; 张东才

    1999-01-01

    In this study, a green fluorescent protein (GFP)-calmodulin (CaM) fusion gene method was used to examine the distribution of calmodulin during various stages of cell cycle. First, it was found that the distribution of CaM in living cells changes with the cell cycle. CaM was found mainly in the cytoplasm during G1 phase. It began to move into the nucleus when the cell entered S phase. At G2 phase, CaM became more concentrated in the nucleus than in cytoplasm. Second, the accumulation of CaM in the nucleus during G2 phase appeared to be related to the onset of mitosis, since inhibiting the activation of CaM at this stage resulted in blocking the nuclear membrane breakdown and chromatin condensation. Finally, after the cell entered mitosis, a high concentration of CaM was found at the polar regions of the mitotic spindle. At this time, inhibiting the activity of CaM would cause a disruption of the spindle structure. The relationship between the stage-specific distribution of CaM and its function in regulat

  17. Regional nodal relapse in surgically staged Merkel cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hoeller, Ulrike; Mueller, Thomas; Schubert, Tina; Budach, Volker; Ghadjar, Pirus [Charite Universitaetsmedizin Berlin, Department of Radiation Oncology, Berlin (Germany); Brenner, Winfried [Charite Universitaetsmedizin Berlin, Department of Nuclear Medicine, Berlin (Germany); Kiecker, Felix [Charite Universitaetsmedizin Berlin, Department of Dermatology, Berlin (Germany); Schicke, Bernd [Tumor Center Berlin, Berlin (Germany); Haase, Oliver [Charite Universitaetsmedizin Berlin, Department of Surgery, Berlin (Germany)

    2014-10-08

    The nodal relapse pattern of surgically staged Merkel cell carcinoma (MCC) with/without elective nodal radiotherapy (RT) was studied in a single institution. A total of 51 patients with MCC, 33 % UICC stage I, 14 % II, 53 % III (4 lymph node metastases of unknown primary) were eligible. All patients had surgical staging: 23 patients sentinel node biopsy (SNB), 22 patients SNB followed by lymphadenectomy (LAD) and 6 patients LAD. In all, 94 % of the primary tumors (PT) were completely resected; 57 % of patients received RT, 51 % of known PT sites, 33 % (8/24 patients) regional RT to snN0 nodes and 68 % (17/27 patients) to pN+ nodes, mean reference dose 51.5 and 50 Gy, respectively. Mean follow-up was 6 years (range 2-14 years). A total of 22 % (11/51) patients developed regional relapses (RR); the 5-year RR rate was 27 %. In snN0 sites (stage I/II), relapse occurred in 5 of 14 nonirradiated vs. none of 8 irradiated sites (p = 0.054), resulting in a 5-year RR rate of 33 % versus 0 % (p = 0.16). The crude RR rate was lower in stage I (12 %, 2/17 patients) than for stage II (43 %, 3/7 patients). In stage III (pN+), RR appeared to be less frequent in irradiated sites (18 %, 3/14 patients) compared with nonirradiated sites (33 %, 3/10 patients, p = 0.45) with 5-year RR rates of 23 % vs. 34 %, respectively. Our data suggest that adjuvant nodal RT plays a major role even if the sentinel nodes were negative. Adjuvant RT of the lymph nodes in patients with stage IIa tumors and RT after LAD in stage III tumors is proposed and should be evaluated prospectively. (orig.) [German] Untersucht wurde das regionaere Rezidivmuster des Merkelzell-Karzinoms (MCC) nach chirurgischem Staging und stadienadaptierter Therapie. Eingeschlossen wurden 51 Patienten mit lokalisiertem MCC: 33 % hatten UICC-Stadium-I-, 14 % -II-, 53 % -III-Tumoren (davon 4 Lymphknotenmetastasen eines unbekannten Primaertumors). Alle Patienten erhielten ein chirurgisches Staging: 23 Waechterlymphknotenbiopsien (SNB

  18. Time course of morphine's effects on adult hippocampal subgranular zone reveals preferential inhibition of cells in S phase of the cell cycle and a subpopulation of immature neurons.

    Science.gov (United States)

    Arguello, A A; Harburg, G C; Schonborn, J R; Mandyam, C D; Yamaguchi, M; Eisch, A J

    2008-11-11

    Opiates, such as morphine, decrease neurogenesis in the adult hippocampal subgranular zone (SGZ), raising the possibility that decreased neurogenesis contributes to opiate-induced cognitive deficits. However, there is an incomplete understanding of how alterations in cell cycle progression and progenitor maturation contribute to this decrease. The present study examined how morphine regulates progenitor cell cycle, cell death and immature SGZ neurons (experiment 1) as well as the progression of SGZ progenitors through key stages of maturation (experiment 2). In experiment 1, mice received sham or morphine pellets (s.c., 0 and 48 h) and bromodeoxyuridine (BrdU) 2 h prior to sacrifice (24, 72 or 96 h). Morphine decreased both the number of S phase and total cycling cells, as there were fewer cells immunoreactive (IR) for the S phase marker BrdU and the cell cycle marker Ki67. The percentage of Ki67-IR cells that were BrdU-IR was decreased after 24 but not 96 h of morphine, suggesting a disproportionate effect on S phase cells relative to all cycling cells at this time point. Cell death (activated caspase-3 counts) was increased after 24 but not 96 h. In experiment 2, nestin-green fluorescent protein (GFP) mice given BrdU 1 day prior to morphine or sham surgery (0 and 48 h, sacrifice 96 h) had fewer Ki67-IR cells, but no change in BrdU-IR cell number, suggesting that this population of BrdU-IR cells was less sensitive to morphine. Interestingly, examination of key stages of progenitor cell maturation revealed that morphine increased the percent of BrdU-IR cells that were type 2b and decreased the percent that were immature neurons. These data suggest that chronic morphine decreases SGZ neurogenesis by inhibiting dividing cells, particularly those in S phase, and progenitor cell progression to a more mature neuronal stage. PMID:18832014

  19. Cell Division, a new open access online forum for and from the cell cycle community

    Directory of Open Access Journals (Sweden)

    Kaldis Philipp

    2006-04-01

    Full Text Available Abstract Cell Division is a new, open access, peer-reviewed online journal that publishes cutting-edge articles, commentaries and reviews on all exciting aspects of cell cycle control in eukaryotes. A major goal of this new journal is to publish timely and significant studies on the aberrations of the cell cycle network that occur in cancer and other diseases.

  20. Entrainability of cell cycle oscillator models with exponential growth of cell mass.

    Science.gov (United States)

    Nakao, Mitsuyuki; Enkhkhudulmur, Tsog-Erdene; Katayama, Norihiro; Karashima, Akihiro

    2014-01-01

    Among various aspects of cell cycle, understanding synchronization mechanism of cell cycle is important because of the following reasons. (1)Cycles of cell assembly should synchronize to form an organ. (2) Synchronizing cell cycles are required to experimental analysis of regulatory mechanisms of cell cycles. (3) Cell cycle has a distinct phase relationship with the other biological rhythms such as circadian rhythm. However, forced as well as mutual entrainment mechanisms are not clearly known. In this study, we investigated entrainability of cell cycle models of yeast cell under the periodic forcing to both of the cell mass and molecular dynamics. Dynamics of models under study involve the cell mass growing exponentially. In our result, they are shown to allow only a limited frequency range for being entrained by the periodic forcing. In contrast, models with linear growth are shown to be entrained in a wider frequency range. It is concluded that if the cell mass is included in the cell cycle regulation, its entrainability is sensitive to a shape of growth curve assumed in the model. PMID:25571564

  1. Periodic synthesis of phospholipids during the Caulobacter crescentus cell cycle.

    OpenAIRE

    O'Neill, E A; Bender, R A

    1987-01-01

    Net phospholipid synthesis is discontinuous during the Caulobacter crescentus cell cycle with synthesis restricted to two discrete periods. The first period of net phospholipid synthesis begins in the swarmer cell shortly after cell division and ends at about the time when DNA replication initiates. The second period of phospholipid synthesis begins at a time when DNA replication is about two-thirds complete and ends at about the same time that DNA replication terminates. Thus, considerable D...

  2. Cell cycle related /sup 125/IUDR-induced-division delay

    International Nuclear Information System (INIS)

    A series of experiments were run to determine if /sup 125/I-decays, in /sup 125/IUdR labeled DNA, specifically accumulated at 1, 3, 5, 7 and 9 hours after plating labeled mitotic cells caused a change in the rate or time of cell entry into mitosis. To accomplish this, a pool of labeled mitotic cells was selected in mitosis and plated in replicate flasks. /sup 125/I decays were accumulated in groups of cells by cooling (40C) for 2 hours starting at the designated times. After rewarding, colcemid was added to arrest cells in mitosis. The rate of cell progression into mitosis for each cell cycle time of accumulation was determined by scoring the mitotic index of cells sampled as a function of time after addition of the colcemid. The results are summarized: (1) Decays from /sup 125/I in /sup 125/I(UdR) labeled DNA reduced the rate of cell progression into mitosis and delayed the time of initiation of mitosis. (2) The reduced rate of progression and the delayed time of initiation of mitosis were independent of the cell cycle time that /sup 125/I-decays were accumulated. (3) The reduced rate of progression after cell cycle accumulation of /sup 125/I decay was statistically indistinguishable from the corresponding controls. (4) The delayed initiation of mitosis after specific cell cycle accumulation of /sup 125/I- decays was greater than the corresponding control. The relationship of these data to DNA and non-DNA division delay target(s) is emphasized

  3. Potent inhibition of late stages of hepadnavirus replication by a modified cell penetrating peptide

    DEFF Research Database (Denmark)

    Abdul, Fabien; Ndeboko, Bénédicte; Buronfosse, Thierry;

    2012-01-01

    Cationic cell-penetrating peptides (CPPs) and their lipid domain-conjugates (CatLip) are agents for the delivery of (uncharged) biologically active molecules into the cell. Using infection and transfection assays we surprisingly discovered that CatLip peptides were able to inhibit replication of...... particle secretion. This is the first report showing that a CPP is able to drastically block hepadnaviral release from infected cells by altering late stages of viral morphogenesis via interference with enveloped particle formation, without affecting naked nucleocapsid egress, thus giving a view inside the...... mode of inhibition. Deca-(Arg)8 may be a useful tool for elucidating the hepadnaviral secretory pathway, which is not yet fully understood. Moreover we provide the first evidence that a modified CPP displays a novel antiviral mechanism targeting another step of viral life cycle compared to what has...

  4. Ionizing radiation and cell cycle progression in ataxia telangiectasia

    International Nuclear Information System (INIS)

    Exposure of mammalian cells to ionizing radiation causes delay in normal progress through the cell cycle at a number of different checkpoints. Abnormalities in these checkpoints have been described for ataxia telangiectasia cells after irradiation. In this report we show that these abnormalities occur at different phases in the cell cycle in several ataxia telangiectasia lymphoblastoid cells. Ataxia telangiectasia cells, synchronized in late G1 phase with either mimosine or aphidicolin and exposed to radiation, showed a reduced delay in entering S phase compared to irradiated control cells. Failure to exhibit G1-phase delay in ataxia telangiectasia cells is accompanied by a reduced ability of radiation to activate the product of the tumor suppressor gene p53, a protein involved in G1/S-phase delay. When the progress of irradiated G1-phase cells was followed into the subsequent G2 and G1 phases ataxia telangiectasia cells showed a more pronounced accumulation in G2 phase than control cells. When cells were irradiated in S phase and extent of delay was more evident in G2 phase and ataxia telangiectasia cells were delayed to a greater extent. These results suggest that the lack of initial delay in both G1 and S phases to the radiosensitivity observed in this syndrome. 26 refs., 3 figs., 2 tabs

  5. Regulation of apoptosis and cell cycle in irradiated mouse brain

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Won Yong; Song, Mi Hee; Hung, Eun Ji; Seong, Jin Sil; Suh, Chang Ok [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    2001-06-01

    To investigate the regulation of apoptosis and cell cycle in mouse brain irradiation. 8-week old male mice, C57B 1/6J were given whole body {gamma} -radiation with a single dose of 25 Gy using Cobalt 60 irradiator. At different times 1, 2, 4, 8 and 24hr after irradiation, mice were killed and brain tissues were collected. Apoptotic cells were scored by TUNEL assay. Expression of p53, Bcl-2, and Bax and cell cycle regulating molecules; cyclins BI, D1, E and cdk2, cdk4, p34{sup cdc2} were analysed by Western blotting. Cell cycle was analysed by flow cytometry. The peak of radiation induced apoptosis is shown at 8 hour after radiation. With a single 25 Gy irradiation, the peak of apoptotic index in C57B1/6J is 24.0{+-}0.25 (p<0.05) at 8 hour after radiation. Radiation upregulated the expression of p53/tubulin, Bax/tubulin, and Bcl-2/tubulin with 1.3, 1.1 and 1.45 fold increase, respectively were shown at the peak level at 8 hour after radiation. The levels of cell cycle regulating molecules after radiation are not changed significantly except cyclin D1 with 1.3 fold increase. Fractions of Go-G 1, G2-M and S phase in the cell cycle does not specific changes by time. In mouse brain tissue, radiation induced apoptosis is particularly shown in a specific area, subependyma. These results and lack of radiation induced changes in cell cycle offer better understanding of radiation response of normal brain tissue.

  6. Regulation of apoptosis and cell cycle in irradiated mouse brain

    International Nuclear Information System (INIS)

    To investigate the regulation of apoptosis and cell cycle in mouse brain irradiation. 8-week old male mice, C57B 1/6J were given whole body γ -radiation with a single dose of 25 Gy using Cobalt 60 irradiator. At different times 1, 2, 4, 8 and 24hr after irradiation, mice were killed and brain tissues were collected. Apoptotic cells were scored by TUNEL assay. Expression of p53, Bcl-2, and Bax and cell cycle regulating molecules; cyclins BI, D1, E and cdk2, cdk4, p34cdc2 were analysed by Western blotting. Cell cycle was analysed by flow cytometry. The peak of radiation induced apoptosis is shown at 8 hour after radiation. With a single 25 Gy irradiation, the peak of apoptotic index in C57B1/6J is 24.0±0.25 (p<0.05) at 8 hour after radiation. Radiation upregulated the expression of p53/tubulin, Bax/tubulin, and Bcl-2/tubulin with 1.3, 1.1 and 1.45 fold increase, respectively were shown at the peak level at 8 hour after radiation. The levels of cell cycle regulating molecules after radiation are not changed significantly except cyclin D1 with 1.3 fold increase. Fractions of Go-G 1, G2-M and S phase in the cell cycle does not specific changes by time. In mouse brain tissue, radiation induced apoptosis is particularly shown in a specific area, subependyma. These results and lack of radiation induced changes in cell cycle offer better understanding of radiation response of normal brain tissue

  7. Non-Small Cell Lung Cancer: Screening, Diagnosis, and Staging

    OpenAIRE

    Ferreira, J; Magalhães, M; Rocha, E; Marques, F

    2012-01-01

    Lung cancer is the leading cause of cancer deaths worldwide. Tobacco consumption is the primary cause of lung cancer, accounting for more than 85% 90% of all lung cancer deaths. Non-small cell lung cancer accounts for about 85% of all lung cancers. Several studies have shown that low-dose helical CT of the lung detects more nodules and lung cancers, including early-stage cancers, than does chest radiography. The National Lung Cancer Screening Trial results show that three annual roun...

  8. Viral infections and cell cycle G2/M regulation

    Institute of Scientific and Technical Information of China (English)

    Richard Y.ZHAO; Robert T.ELDER

    2005-01-01

    Progression of cells from G2 phase of the cell cycle to mitosis is a tightly regulated cellular process that requires activation of the Cdc2 kinase, which determines onset of mitosis in all eukaryotic cells. In both human and fission yeast(Schizosaccharomyces pombe) cells, the activity of Cdc2 is regulated in part by the phosphorylation status of tyrosine 15(Tyr15) on Cdc2, which is phosphorylated by Wee1 kinase during late G2 and is rapidly dephosphorylated by the Cdc25 tyrosine phosphatase to trigger entry into mitosis. These Cdc2 regulators are the downstream targets of two well-characterized G2/M checkpoint pathways which prevent cells from entering mitosis when cellular DNA is damaged or when DNA replication is inhibited. Increasing evidence suggests that Cdc2 is also commonly targeted by viral proteins,which modulate host cell cycle machinery to benefit viral survival or replication. In this review, we describe the effect of viral protein R (Vpr) encoded by human immunodeficiency virus type 1 (HIV-1) on cell cycle G2/M regulation. Based on our current knowledge about this viral effect, we hypothesize that Vpr induces cell cycle G2 arrest through a mechanism that is to some extent different from the classic G2/M checkpoints. One the unique features distinguishing Vpr-induced G2 arrest from the classic checkpoints is the role of phosphatase 2A (PP2A) in Vpr-induced G2 arrest.Interestingly, PP2A is targeted by a number of other viral proteins including SV40 small T antigen, polyomavirus T antigen, HTLV Tax and adenovirus E4orf4. Thus an in-depth understanding of the molecular mechanisms underlying Vpr-induced G2 arrest will provide additional insights into the basic biology of cell cycle G2/M regulation and into the biological significance of this effect during host-pathogen interactions.

  9. Thermal stress cycling of GaAs solar cells

    Science.gov (United States)

    Janousek, B. K.; Francis, R. W.; Wendt, J. P.

    1985-01-01

    A thermal cycling experiment was performed on GaAs solar cells to establish the electrical and structural integrity of these cells under the temperature conditions of a simulated low-Earth orbit of 3-year duration. Thirty single junction GaAs cells were obtained and tests were performed to establish the beginning-of-life characteristics of these cells. The tests consisted of cell I-V power output curves, from which were obtained short-circuit current, open circuit voltage, fill factor, and cell efficiency, and optical micrographs, spectral response, and ion microprobe mass analysis (IMMA) depth profiles on both the front surfaces and the front metallic contacts of the cells. Following 5,000 thermal cycles, the performance of the cells was reexamined in addition to any factors which might contribute to performance degradation. It is established that, after 5,000 thermal cycles, the cells retain their power output with no loss of structural integrity or change in physical appearance.

  10. Labeling of lectin receptors during the cell cycle.

    Science.gov (United States)

    Garrido, J

    1976-12-01

    Labeling of lectin receptors during the cell cycle. (Localizabión de receptores para lectinas durante el ciclo celular). Arch. Biol. Med. Exper. 10: 100-104, 1976. The topographic distribution of specific cell surface receptors for concanavalin A and wheat germ agglutinin was studied by ultrastructural labeling in the course of the cell cycle. C12TSV5 cells were synchronized by double thymidine block or mechanical selection (shakeoff). They were labeled by means of lectin-peroxidase techniques while in G1 S, G2 and M phases of the cycle. The results obtained were similar for both lectins employed. Interphase cells (G1 S, G2) present a stlihtly discontinous labeling pattern that is similar to the one observed on unsynchronized cells of the same line. Cells in mitosis, on the contrary, present a highly discontinous distribution of reaction product. This pattern disappears after the cells enters G1 and is not present on mitotic cells fixed in aldehyde prior to labeling. PMID:1030938

  11. A combined gas cooled nuclear reactor and fuel cell cycle

    Science.gov (United States)

    Palmer, David J.

    Rising oil costs, global warming, national security concerns, economic concerns and escalating energy demands are forcing the engineering communities to explore methods to address these concerns. It is the intention of this thesis to offer a proposal for a novel design of a combined cycle, an advanced nuclear helium reactor/solid oxide fuel cell (SOFC) plant that will help to mitigate some of the above concerns. Moreover, the adoption of this proposal may help to reinvigorate the Nuclear Power industry while providing a practical method to foster the development of a hydrogen economy. Specifically, this thesis concentrates on the importance of the U.S. Nuclear Navy adopting this novel design for its nuclear electric vessels of the future with discussion on efficiency and thermodynamic performance characteristics related to the combined cycle. Thus, the goals and objectives are to develop an innovative combined cycle that provides a solution to the stated concerns and show that it provides superior performance. In order to show performance, it is necessary to develop a rigorous thermodynamic model and computer program to analyze the SOFC in relation with the overall cycle. A large increase in efficiency over the conventional pressurized water reactor cycle is realized. Both sides of the cycle achieve higher efficiencies at partial loads which is extremely important as most naval vessels operate at partial loads as well as the fact that traditional gas turbines operating alone have poor performance at reduced speeds. Furthermore, each side of the cycle provides important benefits to the other side. The high temperature exhaust from the overall exothermic reaction of the fuel cell provides heat for the reheater allowing for an overall increase in power on the nuclear side of the cycle. Likewise, the high temperature helium exiting the nuclear reactor provides a controllable method to stabilize the fuel cell at an optimal temperature band even during transients helping

  12. High efficiency fuel cell/advanced turbine power cycles

    Energy Technology Data Exchange (ETDEWEB)

    Morehead, H. [Westinghouse Electric Corp., Orlando, FL (United States)

    1995-10-19

    An outline of the Westinghouse high-efficiency fuel cell/advanced turbine power cycle is presented. The following topics are discussed: The Westinghouse SOFC pilot manufacturing facility, cell scale-up plan, pressure effects on SOFC power and efficiency, sureCell versus conventional gas turbine plants, sureCell product line for distributed power applications, 20 MW pressurized-SOFC/gas turbine power plant, 10 MW SOFC/CT power plant, sureCell plant concept design requirements, and Westinghouse SOFC market entry.

  13. Evolution of cell cycle control: same molecular machines, different regulation

    DEFF Research Database (Denmark)

    de Lichtenberg, Ulrik; Jensen, Thomas Skøt; Brunak, Søren;

    2007-01-01

    Decades of research has together with the availability of whole genomes made it clear that many of the core components involved in the cell cycle are conserved across eukaryotes, both functionally and structurally. These proteins are organized in complexes and modules that are activated or...... layers of regulation together control the activity of cell cycle complexes and how this regulation has evolved. The results show surprisingly poor conservation of both the transcriptional and the post-translation regulation of individual genes and proteins; however, the changes in one layer of regulation...... are often mirrored by changes in other layers, implying that independent layers of control coevolve. By taking a bird's eye view of the cell cycle, we demonstrate how the modular organization of cellular systems possesses a built-in flexibility, which allows evolution to find many different solutions...

  14. Mediastinal Staging in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Gamliel, Ziv

    2016-07-01

    In the absence of distant metastases, lung cancer treatment is determined by the results of mediastinal lymph node staging. Occult mediastinal lymph node metastases can be missed by radiologic and needle-based staging methods. Aggressive staging of mediastinal lymph nodes improves staging accuracy. Improved accuracy of mediastinal lymph node staging results in more appropriate lung cancer treatment. Improved accuracy of mediastinal lymph node staging can improve stage-specific survival from lung cancer. PMID:27261911

  15. UV-induced changes in cell cycle and gene expression within rabbit lens epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Sidjanin, D. [Northern Illinois Univ., De Kalb, IL (United States). Dept. of Biological Sciences; Grdina, D. [Argonne National Lab., IL (United States); Woloschak, G.E. [Northern Illinois Univ., De Kalb, IL (United States). Dept. of Biological Sciences

    1994-11-01

    Damage to lens epithelial cells is a probable initiation process in cataract formation induced by ultraviolet radiation. These experiments investigated the ability of 254 nm radiation on cell cycle progression and gene expression in rabbit lens epithelial cell line N/N1003A. No changes in expression of c-fos, c-jun, alpha- tubulin, or vimentin was observed following UV exposure. Using flow cytometry, an accumulation of cells in G1/S phase of the cell cycle 1 hr following exposure. The observed changes in gene expression, especially the decreased histone transcripts reported here may play a role in UV induced inhibition of cell cycle progression.

  16. Stage I squamous cell carcinoma of the vulva

    Energy Technology Data Exchange (ETDEWEB)

    Simonsen, E.; Johnsson, J.E.; Trope, C.; Alm, P.; Ranstam, J.

    1984-01-01

    Eighty-six patients with invasive squamous cell carcinoma of the vulva stage I were followed for 2 to 20 years after surgical treatment varying from local excision to radical vulvectomy with inguinal lymph node dissection. The results are presented and the prognosis discussed in relation to the radicality of the surgical intervention, the degree of tumour differentiation, the morphologic properties of tumour cell population, and the tumour host relationship. The most important prognostic factor seemed to be the radicality of the surgical intervention. To reduce patient morbidity in radical surgery while still achieving a comparable survival rate an operative approach with less than radical vulvectomy, inguinal dissections or pelvic lymphadenectomy, or both, is proposed for selected patients. (orig.).

  17. Stage I squamous cell carcinoma of the vulva

    International Nuclear Information System (INIS)

    Eighty-six patients with invasive squamous cell carcinoma of the vulva stage I were followed for 2 to 20 years after surgical treatment varying from local excision to radical vulvectomy with inguinal lymph node dissection. The results are presented and the prognosis discussed in relation to the radicality of the surgical intervention, the degree of tumour differentiation, the morphologic properties of tumour cell population, and the tumour host relationship. The most important prognostic factor seemed to be the radicality of the surgical intervention. To reduce patient morbidity in radical surgery while still achieving a comparable survival rate an operative approach with less than radical vulvectomy, inguinal dissections or pelvic lymphadenectomy, or both, is proposed for selected patients. (orig.)

  18. Influence of chlorine dioxide on cell death and cell cycle of human gingival fibroblasts

    OpenAIRE

    Nishikiori, Ryo; Nomura, Yuji; Sawajiri, Masahiko; Masuki, Kohei; Hirata, Isao; Okazaki, Masayuki

    2008-01-01

    Objectives: The effects of chlorine dioxide (ClO2), sodium hypochlorite (NaOCl), and hydrogen peroxide (H2O2) on cell death and the cell cycle of human gingival fibroblast (HGF) cells were examined. Methods: The inhibition of HGF cell growth was evaluated using a Cell Counting Kit-8. The cell cycle was assessed with propidium iodide-stained cells (distribution of cells in G0/G1, S, G2/M phases) using flow cytometry. The patterns of cell death (necrosis and apoptosis) were analyzed using f...

  19. Thermodynamic analysis and optimization of a two-stage organic Rankine cycle for liquefied natural gas cryogenic exergy recovery

    International Nuclear Information System (INIS)

    A two-stage ORC (organic Rankine cycle) is proposed, by which low-grade heat of exhaust flue gas of a 123.5 MW gas-steam combined cycle power generating unit, as well as the cryogenic energy of LNG (liquefied natural gas) can be effectively recovered and utilized. R227ea and R116 are selected as working fluids for the system. Based on the thermodynamic mathematical models, the effects of key design parameters, including that of turbine inlet pressures, mass flow rates of working fluids and outlet steam fractions of evaporators on the system performance are investigated from the view of both thermodynamics and economics with CPP (cost per net power output) as the objective function. The results obtained the optimal inlet pressure of turbines, under which, the CPP has the minimum value. It is found that the CPP also decreases with the mass flow rate of R227ea and R116. The rate of absorbed heat in top cycle to that in bottom cycle has a positive impact on CPP, but very weak. The optimized two-stage ORC system can output net work with 1776.44 kW with the thermal efficiency of 25.64% and exergy efficiency of 31.02%. Cost per net power output is 6.3$/W, while the LNG temperature can be raised to 283.15 K. - Highlights: • Two-stage organic Rankine cycle is proposed to recover both exhaust heat of flue gas and LNG cryogenic exergy. • Flue gas from a gas-steam combined cycle power plant and LNG are employed as heat source and heat sink, respectively. • Thermodynamic and economic mathematical models are established. • Parameter optimization is studied and optimal design with the CPP of 6.3$/W is obtained. • Effects of key thermodynamic design parameters on system performance are investigated

  20. Evolution of cell cycle control: same molecular machines, different regulation

    DEFF Research Database (Denmark)

    de Lichtenberg, Ulrik; Jensen, Thomas Skøt; Brunak, Søren; Bork, Peer; Jensen, Lars Juhl

    layers of regulation together control the activity of cell cycle complexes and how this regulation has evolved. The results show surprisingly poor conservation of both the transcriptional and the post-translation regulation of individual genes and proteins; however, the changes in one layer of regulation...... are often mirrored by changes in other layers, implying that independent layers of control coevolve. By taking a bird's eye view of the cell cycle, we demonstrate how the modular organization of cellular systems possesses a built-in flexibility, which allows evolution to find many different solutions...... for assembling the same molecular machines just in time for action....

  1. E2F-1 has dual roles depending on the cell cycle

    Directory of Open Access Journals (Sweden)

    Fikret Sahin, Todd L. Sladek

    2010-01-01

    Full Text Available The E2F family of transcription factors play a critical role in the control of cell proliferation. E2F-1 is the major cellular target of pRB and is regulated by pRB during cell proliferation. E2F-1-mediated activation and repression of target genes occurs in different settings. The role of E2F-1 and E2F-1/pRB complexes in regulation of different target genes, and in cycling versus quiescent cells, is unclear. In this study, effects of free E2F-1 (doesn't complex with pRb and E2F-1/pRb complex, on E2F-1 target gene expression were compared in different cell growth conditions. Findings suggest that E2F-1 acts in different ways, not only depending on the target gene but also depending on different stages of the cell cycle. For example, E2F-1 acts as part of the repression complex with pRB in the expression of DHFR, b-myb, TK and cdc2 in asynchronously growing cells; on the other hand, E2F-1 acts as an activator in the expression of the same genes in cells that are re-entering the cycle.

  2. Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-04-05

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma; Stage IIIA Lung Adenocarcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Large Cell Lung Carcinoma; Stage IIIB Lung Adenocarcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Non-Small Cell Lung Cancer

  3. Fucci2a: a bicistronic cell cycle reporter that allows Cre mediated tissue specific expression in mice.

    Science.gov (United States)

    Mort, Richard Lester; Ford, Matthew Jonathan; Sakaue-Sawano, Asako; Lindstrom, Nils Olof; Casadio, Angela; Douglas, Adam Thomas; Keighren, Margaret Anne; Hohenstein, Peter; Miyawaki, Atsushi; Jackson, Ian James

    2014-01-01

    Markers of cell cycle stage allow estimation of cell cycle dynamics in cell culture and during embryonic development. The Fucci system incorporates genetically encoded probes that highlight G1 and S/G2/M phases of the cell cycle allowing live imaging. However the available mouse models that incorporate Fucci are beset by problems with transgene inactivation, varying expression level, lack of conditional potential and/or the need to maintain separate transgenes-there is no transgenic mouse model that solves all these problems. To address these shortfalls we re-engineered the Fucci system to create 2 bicistronic Fucci variants incorporating both probes fused using the Thosea asigna virus 2A (T2A) self cleaving peptide. We characterize these variants in stable 3T3 cell lines. One of the variants (termed Fucci2a) faithfully recapitulated the nuclear localization and cell cycle stage specific florescence of the original Fucci system. We go on to develop a conditional mouse allele (R26Fucci2aR) carefully designed for high, inducible, ubiquitous expression allowing investigation of cell cycle status in single cell lineages within the developing embryo. We demonstrate the utility of R26Fucci2aR for live imaging by using high resolution confocal microscopy of ex vivo lung, kidney and neural crest development. Using our 3T3 system we describe and validate a method to estimate cell cycle times from relatively short time-lapse sequences that we then apply to our neural crest data. The Fucci2a system and the R26Fucci2aR mouse model are compelling new tools for the investigation of cell cycle dynamics in cell culture and during mouse embryonic development. PMID:25486356

  4. The Coordination of Centrosome Reproduction with Nuclear Events of the Cell Cycle in the Sea Urchin Zygote

    OpenAIRE

    Hinchcliffe, Edward H.; Cassels, Grizzel O.; Rieder, Conly L.; Sluder, Greenfield

    1998-01-01

    Centrosomes repeatedly reproduce in sea urchin zygotes arrested in S phase, whether cyclin-dependent kinase 1–cyclin B (Cdk1-B) activity remains at prefertilization levels or rises to mitotic values. In contrast, when zygotes are arrested in mitosis using cyclin B Δ-90, anaphase occurs at the normal time, yet centrosomes do not reproduce. Together, these results reveal the cell cycle stage specificity for centrosome reproduction and demonstrate that neither the level nor the cycling of Cdk1-B...

  5. Staging and differential diagnosis of renal cell carcinoma

    International Nuclear Information System (INIS)

    The usefulness of magnetic resonance imaging (MRI) was compared with that of computed tomography (CT). Twenty-nine patients with renal cell carcinoma, 3 with angiomyolipomas and 1 with renal pelvic cancer, were examined by both MRI and CT. MRI and CT showed similar results in staging cases of renal cell carcinoma. However, MRI may be more sensitive in detecting the venous extension, metastatic adenopathy, and adjacent organ invasion. In predicting the involvement of perinephric fat, however, MRI is only marginally superior to CT. To demonstrate the usefulness of MRI in differentiating renal cell carcinoma from other renal tumors, the density of renal tumor and that of the psoas muscle were determined using a densitiometer, and the percent (%) contrast (the intensity of the renal tumor / the intensity of the psoas muscle x100) was calculated. In most patients with clear cell type renal carcinoma, the % contrast value in the T1 weighted images was about 100. In the T2 weighted images, the maximum value of the % contrast value was 50 or less in most patients. In one patient with spindle cell type (sarcomatoid type) carcinoma, the % contrast value was 109 in the T1 weighted images, but was 65 - 85, at most, in the T2 weighted images. In patients with renal angiomyolipomas, the % contrast values were calculated exclusive of the fatty components. The % contrast value of the T1 weighted images was 50 or less in all 3 patients, and that of the T2 weighted images was 50 or more in 2 patients and 21 - 38 in the others. Calculation of the % contrast value may possibly enable one to differentiate between various types of renal cell carcinoma and other renal masses. (author)

  6. Effects of cell cycle noise on excitable gene circuits

    CERN Document Server

    Veliz-Cuba, Alan; Bennett, Matthew R; Josić, Krešimir; Ott, William

    2016-01-01

    We assess the impact of cell cycle noise on gene circuit dynamics. For bistable genetic switches and excitable circuits, we find that transitions between metastable states most likely occur just after cell division and that this concentration effect intensifies in the presence of transcriptional delay. We explain this concentration effect with a 3-states stochastic model. For genetic oscillators, we quantify the temporal correlations between daughter cells induced by cell division. Temporal correlations must be captured properly in order to accurately quantify noise sources within gene networks.

  7. Divergence to apoptosis from ROS induced cell cycle arrest: Effect of cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Soumya; Kundu, Subhadip; Sengupta, Suman [Department of Environmental Science, University of Kalyani, West Bengal 741235 (India); Department of Zoology, University of Calcutta, Calcutta-700019, West Bengal (India); Bhattacharyya, Arindam, E-mail: arindam19@yahoo.com [Department of Environmental Science, University of Kalyani, West Bengal 741235 (India); Department of Zoology, University of Calcutta, Calcutta-700019, West Bengal (India)

    2009-04-26

    Recently, the role of cadmium (Cd) in immunosupression has gained importance. Nevertheless, the signaling pathways underlying cadmium-induced immune cell death remains largely unclear. In accordance to our previous in vivo report, and to evaluate the further details of the mechanism, we have investigated the effects of cadmium (CdCl{sub 2}, H{sub 2}O) on cell cycle regulation and apoptosis in splenocytes in vitro. Our results have revealed that reactive oxygen species (ROS) and p21 are involved in cell cycle arrest in a p53 independent manner but late hour apoptotic response was accompanied by the p53 up-regulation, loss of mitochondrial transmembrane potential (MTP), down-regulation of Bcl-xl, activation of caspase-3 and release of cytochrome c (Cyt c). However, pifithrin alfa (PFT-{alpha}), an inhibitor of p53, fails to rescue the cells from the cadmium-induced cell cycle arrest but prevents Bcl-xl down-regulation and loss of {Delta}{psi}{sub m}, which indicates that there is an involvement of p53 in apoptosis. In contrast, treatment with N-acetyl cysteine (NAC) can prevent cell cycle arrest and p21 up-regulation at early hours. Although it is clear that, NAC has no effect on apoptosis, p53 expression and MPT changes at late stage events. Taken together, we have demonstrated that cadmium promotes ROS generation, which potently initiates the cell cycle arrest at early hours and finally induces p53-dependent apoptosis at later part of the event.

  8. Cell cycle control of DNA joint molecule resolution.

    Science.gov (United States)

    Wild, Philipp; Matos, Joao

    2016-06-01

    The establishment of stable interactions between chromosomes underpins vital cellular processes such as recombinational DNA repair and bipolar chromosome segregation. On the other hand, timely disengagement of persistent connections is necessary to assure efficient partitioning of the replicated genome prior to cell division. Whereas great progress has been made in defining how cohesin-mediated chromosomal interactions are disengaged as cells prepare to undergo chromosome segregation, little is known about the metabolism of DNA joint molecules (JMs), generated during the repair of chromosomal lesions. Recent work on Mus81 and Yen1/GEN1, two conserved structure-selective endonucleases, revealed unforeseen links between JM-processing and cell cycle progression. Cell cycle kinases and phosphatases control Mus81 and Yen1/GEN1 to restrain deleterious JM-processing during S-phase, while safeguarding chromosome segregation during mitosis. PMID:26970388

  9. Ovarian Follicular Fluid Constituents in Relation to Stage of Estrus Cycle and Size of the Follicle in Buffalo

    OpenAIRE

    Hussein H. A.; M. R.; Abd Ellah; Derar; D. R.

    2010-01-01

    The goal of the present study was to evaluate the difference in constituent of the ovarian follicular fluid in different stages of the estrus cycle and in medium and large sized follicle and also to evaluate the relation between serum and follicular fluid constituents in cyclic buffalos. A total of 34 clinically healthy buffalo (Bubals bubals), aged 7-10 years, were sent for slaughter in Moesha Abattoir, Assiut province in winter 2009. Blood samples and the whole genital tract of each animal ...

  10. Are technological gatekeepers constraining my cluster? Unfolding the paradox of gatekeepers resilience across cluster life cycle stages

    OpenAIRE

    Jose-Luis Hervas-Oliver

    2012-01-01

    The economic geography literature assumes that large leading firms (technology gatekeepers)(TGs) with high absorptive capacity and high-intensity R&D expenditures, shape the district learning process. However, there is an absence in the literature of a dynamic analysis of the role of the TG. Instead, most of the evidence provided is set at a single point in time and considers only one stage of the cluster life cycle (CLC). This paper challenges the aforementioned assumption, and introduces in...

  11. Targeting the life cycle stages of the Diamond Black Moth (Plutella Xylostella) with three different parasitoid wasps

    OpenAIRE

    Faithpraise, F O; Idung, J; Chatwin, C R; Young, R C D; Birch, P.

    2014-01-01

    A continuous time model of the interaction between crop insect pests and naturally beneficial pest enemies is created using a set of simultaneous, non-linear, ordinary differential equations incorporating natural death rates based on the Weibull distribution. The crop pest is present in all its life-cycle stages of: egg, larva, pupa and adult. The beneficial insects, parasitoid wasps, may be present in either or all parasitized: eggs, larva and pupa. Population modelling is used to estimate t...

  12. Management accounting and control systems used by R&D intensive firms in different organizational life-cycle stages

    OpenAIRE

    Silvola, H. (Hanna)

    2007-01-01

    Abstract This dissertation investigates the use of management accounting and control systems in R&D intensive firms in different organizational life-cycle stages. The thesis consists of four essays focusing on two categories of management accounting and control systems: capital budgeting decisions and management control systems. First, we investigate the evaluation and financing of investment projects in R&D intensive firms. Second, we moreover investigate how R&D intensive fir...

  13. Preoperative concurrent chemoradiotherapy for unresectable stage III nonsmall cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: We carried out a Phase II trial in an attempt to improve resectability and survivability of inoperable Stage III A and III B nonsmall cell lung cancer (NSCLC) patients by implementing a neoadjuvant chemoradiotherapy treatment program. Methods and Materials: Thirty-six patients with locally advanced Stage III NSCLC received neoadjuvant therapy consisting of 50.4 Gy in 5.5 weeks concurrent with two cycles of chemotherapy, using cisplatin and etoposide. No postsurgical consolidation therapy was given. Results: Assessment at 3 to 6 weeks after treatment suggested that 26 (72%) patients had been rendered resectable. Toxicities were common but usually tolerable; however, one toxic death occurred. Of 24 patients who proceeded to thoracotomy, complete resection was achieved in 20 (56%). There were two surgically related deaths. Surgical-pathological staging showed downstaging in 18 patients, including complete sterilization of the tumor in 3 (8%). The median survival for all 36 patients is 15 months, but at the time of analysis, median survival of resectable patients had not been reached. The actuarial 2-year survival is 39% for all study groups, 57% for resectable patients, and 16% for the remaining (p < 0.005). Conclusions: While this preoperative neoadjuvant appears to improve survival of patients with Stage III NSCLC, comparison with previous reports of other similar trials indicate a superior survival advantage in association with higher doses of radiotherapy

  14. Plant Characteristics of an Integrated Solid Oxide Fuel Cell Cycle and a Steam Cycle

    DEFF Research Database (Denmark)

    Rokni, Masoud

    2010-01-01

    Plant characteristics of a system containing a solid oxide fuel cell (SOFC) cycle on the top of a Rankine cycle were investigated. Natural gas (NG) was used as the fuel for the plant. A desulfurization reactor removes the sulfur content in the fuel, while a pre-reformer broke down the heavier...... hydrocarbons in an adiabatic steam reformer (ASR). The pre-treated fuel then entered to the anode side of the SOFC. The remaining fuels after the SOFC stacks entered a catalytic burner for further combusting. The burned gases from the burner were then used to produce steam for the Rankine cycle in a heat...... and the pre-reformer reactor had no effect on the plant efficiency, which was also true when decreasing the anode temperature. However, increasing the cathode temperature had a significant effect on the plant efficiency. In addition, decreasing the SOFC utilization factor from 0.8 to 0.7, increases...

  15. Life cycle assessment of hydrogen production and fuel cell systems

    International Nuclear Information System (INIS)

    This paper details life cycle assessment (LCA) of hydrogen production and fuel cell system. LCA is a key tool in hydrogen and fuel cell technologies for design, analysis, development; manufacture, applications etc. Energy efficiencies and greenhouse gases and air pollution emissions have been evaluated in all process steps including crude oil and natural gas pipeline transportation, crude oil distillation, natural gas reprocessing, wind and solar electricity generation , hydrogen production through water electrolysis and gasoline and hydrogen distribution and utilization

  16. Testing a Mathematical Model of the Yeast Cell Cycle

    OpenAIRE

    Cross, Frederick R.; Archambault, Vincent; Miller, Mary; Klovstad, Martha

    2002-01-01

    We derived novel, testable predictions from a mathematical model of the budding yeast cell cycle. A key qualitative prediction of bistability was confirmed in a strain simultaneously lacking cdc14 and G1 cyclins. The model correctly predicted quantitative dependence of cell size on gene dosage of the G1 cyclin CLN3, but it incorrectly predicted strong genetic interactions between G1 cyclins and the anaphase- promoting complex specificity factor Cdh1. To provide cons...

  17. Intercellular communication is cell cycle modulated during early Xenopus laevis development

    OpenAIRE

    1990-01-01

    We investigated intercellular communication during the seventh and tenth cell cycles of Xenopus laevis development using microinjection of Lucifer yellow and FITC-dextran as well as freeze-fracture electron microscopy. We found that gap junction-mediated dye coupling visualized using Lucifer yellow was strongly cell cycle modulated in the tenth cell cycle. Cytoplasmic bridge-mediated dye coupling visualized via FITC-dextran was also, of course, cell cycle modulated. The basis of cell cycle-mo...

  18. Technoeconomy of different solid oxide fuel cell based hybrid cycle

    DEFF Research Database (Denmark)

    Rokni, Masoud

    2014-01-01

    Gas turbine, steam turbine and heat engine (Stirling engine) is used as bottoming cycle for a solid oxide fuel cell plant to compare different plants efficiencies, CO2 emissionsand plants cost in terms of $/kW. Each plant is then integrated with biomass gasification and finally six plants...

  19. Refined life-cycle assessment of polymer solar cells

    DEFF Research Database (Denmark)

    Lenzmann, F.; Kroon, J.; Andriessen, R.; Espinosa Martinez, Nieves; Garcia-Valverde, R.; Krebs, Frederik C; Ossenbrink, H.; Jager-Waldau, A.; Helm, P.

    A refined life-cycle assessment of polymer solar cells is presented with a focus on critical components, i.e. the transparent conductive ITO layer and the encapsulation components. This present analysis gives a comprehensive sketch of the full environmental potential of polymer-OPV in comparison...

  20. Life cycle sustainability of solid oxide fuel cells: From methodological aspects to system implications

    Science.gov (United States)

    Mehmeti, Andi; McPhail, Stephen J.; Pumiglia, Davide; Carlini, Maurizio

    2016-09-01

    This study reviews the status of life cycle assessment (LCA) of Solid Oxide Fuel Cells (SOFCs) and methodological aspects, communicates SOFC environmental performance, and compares the environmental performance with competing power production technologies using a life cycle perspective. Results indicate that power generation using SOFCs can make a significant contribution to the aspired-to greener energy future. Despite superior environmental performance, empirical studies indicate that economic performance is predominantly the highest-ranked criterion in the decision making process. Future LCA studies should attempt to employ comprehensive dynamic multi-criteria environmental impact analysis coupled with economic aspects, to allow a robust comparison of results. A methodology framework is proposed to achieve simultaneously ambitious socio-economic and environmental objectives considering all life cycle stages and their impacts.

  1. Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence.

    Science.gov (United States)

    Chen, San-Yuan; Liu, Geng-Hung; Chao, Wen-Ying; Shi, Chung-Sheng; Lin, Ching-Yen; Lim, Yun-Ping; Lu, Chieh-Hsiang; Lai, Peng-Yeh; Chen, Hau-Ren; Lee, Ying-Ray

    2016-01-01

    Oral squamous cell carcinoma (OSCC), an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL), a natural compound isolated from Piper longum L., in human OSCC cells. The effects of PL on cell proliferation, the cell cycle, apoptosis, senescence and reactive oxygen species (ROS) levels in human OSCC cells were investigated. PL effectively inhibited cell growth, caused cell cycle arrest and induced apoptosis and senescence in OSCC cells. Moreover, PL-mediated anti-human OSCC behavior was inhibited by an ROS scavenger N-acetyl-l-cysteine (NAC) treatment, suggesting that regulation of ROS was involved in the mechanism of the anticancer activity of PL. These findings suggest that PL suppresses tumor growth by regulating the cell cycle and inducing apoptosis and senescence and is a potential chemotherapy agent for human OSCC cells. PMID:27120594

  2. Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence

    Directory of Open Access Journals (Sweden)

    San-Yuan Chen

    2016-04-01

    Full Text Available Oral squamous cell carcinoma (OSCC, an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL, a natural compound isolated from Piper longum L., in human OSCC cells. The effects of PL on cell proliferation, the cell cycle, apoptosis, senescence and reactive oxygen species (ROS levels in human OSCC cells were investigated. PL effectively inhibited cell growth, caused cell cycle arrest and induced apoptosis and senescence in OSCC cells. Moreover, PL-mediated anti-human OSCC behavior was inhibited by an ROS scavenger N-acetyl-l-cysteine (NAC treatment, suggesting that regulation of ROS was involved in the mechanism of the anticancer activity of PL. These findings suggest that PL suppresses tumor growth by regulating the cell cycle and inducing apoptosis and senescence and is a potential chemotherapy agent for human OSCC cells.

  3. NSA2, a novel nucleolus protein regulates cell proliferation and cell cycle

    International Nuclear Information System (INIS)

    NSA2 (Nop seven-associated 2) was previously identified in a high throughput screen of novel human genes associated with cell proliferation, and the NSA2 protein is evolutionarily conserved across different species. In this study, we revealed that NSA2 is broadly expressed in human tissues and cultured cell lines, and located in the nucleolus of the cell. Both of the putative nuclear localization signals (NLSs) of NSA2, also overlapped with nucleolar localization signals (NoLSs), are capable of directing nucleolar accumulation. Moreover, over-expression of the NSA2 protein promoted cell growth in different cell lines and regulated the G1/S transition in the cell cycle. SiRNA silencing of the NSA2 transcript attenuated the cell growth and dramatically blocked the cell cycle in G1/S transition. Our results demonstrated that NSA2 is a nucleolar protein involved in cell proliferation and cell cycle regulation.

  4. Helquat dye for staining dead cells, fluorescence activated cell sorting (FACS) and cell cycle analysis

    Czech Academy of Sciences Publication Activity Database

    Joshi, Vishwas; Kužmová, Erika; Kozák, Jaroslav; Bednárová, Lucie; Císařová, I.; Hájek, Miroslav; Teplý, Filip

    Praha: Czech Chemical Society, 2015. s. 86. [Liblice 2015. Advances in Organic , Bioorganic and Pharmaceutical Chemistry /50./. 06.11.2015-08.11.2015, Olomouc] R&D Projects: GA ČR GA13-19213S Institutional support: RVO:61388963 Keywords : helquat dye * FACS * cell cycle analysis Subject RIV: CC - Organic Chemistry

  5. Detection, staging and clinical implications of renal cell carcinoma

    International Nuclear Information System (INIS)

    To compare the epidemiologic, clinical and pathologic characteristics of symptomatic and incidental renal cell carcinoma (RCC)in Jordan.Results were compared with published Western figure. Records of 119 patients with renal tumors diagnosed during the period January1992 to December 2001at Jordan University of Science and Technology, Irbid, Jordan were reviewed. Age,gender, radiologic and biologic workup, treatment,features of tumor were reviewed. The mean patient age was 54 and the male to female ratio was 3.4:1. 26% of tumors were discoverd accidentlly.The incidental detction group had significantly small size of tumor.,lower stage and lower histological grading.In symptomatic group woman have significantly lower mean size of tumor than men. A radical nephrectomy was performed in 92% of the cases, and in 8% of the cases, conservative mangement was adopted. The present study showed that the incidence rate of RCC in Jordan is less than Western countries. Significant number of RCC were detected incidently with lower pathological stage and grade. Subsequently these clinically and histologically less aggressive lesions lead to better survival. These data efforts should be directed to the devlopment of screening protocol to detect these lesions early. (author)

  6. Coal in a sustainable society. Stage 1: life cycle analysis of steel and electricity production in Australia

    International Nuclear Information System (INIS)

    This article reports on the first stage of a larger project aimed at understanding and supporting coal's role in a sustainable society. In this stage, the impacts of steel and electricity production in Australia were considered in a sustainability context by using: 1. Life cycle analysis (LCA) to determine environmental impacts based on greenhouse gas emissions, SOx, NOx, suspended particulate matter (SPM) emissions and fresh water consumption-including the key issues identified in the 1999 UNEP assessment of global issues [UNEP 1999]. A much wider range of impacts is being considered in Stage II of the study. 2. A qualitative assessment of social impacts, not based on LCA. 3. A quantitative assessment of the greenhouse effects on economics, based on a range of hypothetical carbon equivalent penalties. While this paper reports only the LCA part of the study, the full report is available from www.sustainabletechnology.com.au. Copyright (2000) CSIRO Energy Technology and Exploration and Mining

  7. Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer

    International Nuclear Information System (INIS)

    Standard therapy for metastatic non small cell lung cancer (NSCLC) includes palliative systemic chemotherapy and/or radiotherapy. Recent studies of patients with limited metastases treated with curative-intent stereotactic body radiation therapy (SBRT) have shown encouraging survival. We hypothesized that patients treated with SBRT for limited metastases have comparable outcomes with those treated with curative-intent radiation for Stage III NSCLC. We retrospectively reviewed the records of NSCLC patients treated with curative-intent radiotherapy at the University of Rochester from 2000-2008. We identified 3 groups of patients with NSCLC: stage III, stage IV, and recurrent stage IV (initial stage I-II). All stage IV NSCLC patients treated with SBRT had ≤ 8 lesions. Of 146 patients, 88% had KPS ≥ 80%, 30% had > 5% weight loss, and 95% were smokers. The 5-year OS from date of NSCLC diagnosis for stage III, initial stage IV and recurrent stage IV was 7%, 14%, and 27% respectively. The 5-year OS from date of metastatic diagnosis was significantly (p < 0.00001) superior among those with limited metastases (≤ 8 lesions) versus stage III patients who developed extensive metastases not amenable to SBRT (14% vs. 0%). Stage IV NSCLC is a heterogeneous patient population, with a selected cohort apparently faring better than Stage III patients. Though patients with limited metastases are favorably selected by virtue of more indolent disease and/or less bulky disease burden, perhaps staging these patients differently is appropriate for prognostic and treatment characterization. Aggressive local therapy may be indicated in these patients, though prospective clinical studies are needed

  8. Tocilizumab unmasks a stage-dependent interleukin-6 component in statin-induced apoptosis of metastatic melanoma cells.

    Science.gov (United States)

    Minichsdorfer, Christoph; Wasinger, Christine; Sieczkowski, Evelyn; Atil, Bihter; Hohenegger, Martin

    2015-08-01

    The interleukin (IL)-6 inhibits the growth of early-stage melanoma cells, but not metastatic cells. Metastatic melanoma cells are susceptible to statin-induced apoptosis, but this is not clear for early-stage melanoma cells. This study aimed to investigate the IL-6 susceptibility of melanoma cells from different stages in the presence of simvastatin to overcome loss of growth arrest. ELISA was used to detect secreted IL-6 in human melanoma cells. The effects of IL-6 were measured by western blots for STAT3 and Bcl-2 family proteins. Apoptosis and proliferation were measured by caspase 3 activity, Annexin V staining, cell cycle analysis, and a wound-healing assay. Human metastatic melanoma cells A375 and 518A2 secrete high amounts of IL-6, in contrast to early-stage WM35 cells. Canonical IL-6 signaling is intact in these cells, documented by transient phosphorylation of STAT3. Although WM35 cells are highly resistant to simvastatin-induced apoptosis, coadministration with IL-6 enhanced the susceptibility to undergo apoptosis. This proapoptotic effect of IL-6 might be explained by a downregulation of Bcl-XL, observed only in WM35 cells. Furthermore, the IL-6 receptor blocking antibody tocilizumab was coadministered and unmasked an IL-6-sensitive proportion in the simvastatin-induced caspase 3 activity of metastatic melanoma cells. These results confirm that simvastatin facilitates apoptosis in combination with IL-6. Although endogenous IL-6 secretion is sufficient in metastatic melanoma cells, exogenously added IL-6 is needed for WM35 cells. This effect may explain the failure of simvastatin to reduce melanoma incidence in clinical trials and meta-analyses. PMID:26020489

  9. The Interplay between Cell Wall Mechanical Properties and the Cell Cycle in Staphylococcus aureus

    OpenAIRE

    Bailey, Richard G.; Turner, Robert D.; Mullin, Nic; Clarke, Nigel,; Foster, Simon J.; Hobbs, Jamie K.

    2014-01-01

    The nanoscale mechanical properties of live Staphylococcus aureus cells during different phases of growth were studied by atomic force microscopy. Indentation to different depths provided access to both local cell wall mechanical properties and whole-cell properties, including a component related to cell turgor pressure. Local cell wall properties were found to change in a characteristic manner throughout the division cycle. Splitting of the cell into two daughter cells followed a local softe...

  10. Changes in phosphorylation pattern of regulatory proteins after X-irradiation of mouse embryos during 2-cell stage

    International Nuclear Information System (INIS)

    Phosphoproteins are the major key molecules responsible for the regulation of the complex network of cellular responses to external signals. Especially the signal transduction pathways and the control of the cell cycle are regulated by phosphorylated enzymes and substrate molecules. Studies have identified the phosphorylation of tyrosine residues to be one of the crucial mechanisms mediating the proliferation and differentiation of cells. The aim of our study was to analyze the patterns of phosphoproteins of murine preimplantation embryos after irradiation with various doses (3-6 Gy). We tried to find out if there are changes in phosphorylation patterns at the transition from the four-cell stage to the eight-cell stage which are a result of a dose dependent radiation effect. Investigations were made to prove which influence X-irradiation has on regulatory mechanisms during the third cell cycle. We tried to characterize proteins with an altered phosphorylation pattern to find out if these proteins could be regulatory elements involved in the cell cycle control. (author)

  11. GLI1 is involved in cell cycle regulation and proliferation of NT2 embryonal carcinoma stem cells

    DEFF Research Database (Denmark)

    Vestergaard, Janni; Lind-Thomsen, Allan; Pedersen, Mikkel W.;

    2008-01-01

    of altered HH signaling are interpreted by specific cell types. We have investigated the role of the HH transcription factor glioma-associated oncogene homolog 1 (GLI1) in the human Ntera2=D1 (NT2) embryonal carcinoma stem cell line. The study revealed that expression of GLI1 and its direct transcriptional...... target Patched (PTCH) is downregulated in the early stages of retinoic acid-induced neuronal differentiation of NT2 cells. To identify transcriptional targets of the HH transcription factor GLI1 in NT2 cells, we performed global expression profiling following GLI1 RNA interference (RNAi). Of the similar...... to 8500 transcripts represented on the microarrays, expression of 88 genes was downregulated and expression of 26 genes was upregulated. Nineteen of these genes are involved in cell cycle and proliferation. Further, GLI1 RNAi leads to a significant decrease in NT2 proliferation and changes expression of G...

  12. Pre-operative concurrent chemoradiotherapy for stage IIIA (N2) Non-Small cell lung cancer

    International Nuclear Information System (INIS)

    This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45-67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in 12, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal lymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intraventous cis-Platin (100 mg/m2) on day 1 and oral Etoposide (50 mg/m2/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred in 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/13) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post-operative tumor

  13. Pre-operative concurrent chemoradiotherapy for stage IIIA (N2) Non-Small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyu Chan; Ahn, Yong Chan; Park, Keun Chil [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)] [and others

    1999-06-01

    This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45-67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in 12, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal lymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intraventous cis-Platin (100 mg/m{sup 2}) on day 1 and oral Etoposide (50 mg/m{sup 2}/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred in 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/13) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post

  14. Anticancer effect of arsenite on cell migration, cell cycle and apoptosis in human pancreatic cancer cells

    Science.gov (United States)

    HORIBE, YOHEI; ADACHI, SEIJI; YASUDA, ICHIRO; YAMAUCHI, TAKAHIRO; KAWAGUCHI, JUNJI; KOZAWA, OSAMU; SHIMIZU, MASAHITO; MORIWAKI, HISATAKA

    2016-01-01

    The standard treatment for advanced pancreatic cancer is chemotherapy, but its clinical outcome remains unsatisfactory. Therefore, the development of novel treatments for this malignancy is urgently required. In the present study, the anticancer effect of arsenite on platelet-derived growth factor (PDGF)-BB-induced migration, cell cycle and apoptosis was investigated in pancreatic cancer cells (AsPC-1 and BxPC-3), and compared with the effect on normal pancreatic epithelial (PE) cells. In the cell migration assay, arsenite clearly inhibited PDGF-BB-induced cell migration in AsPC-1 cells, but not in BxPC-3 or PE cells. Arsenite also caused cell apoptosis in AsPC-1 cells, but not in BxPC-3 or PE cells. In AsPC-1 cells, the levels of cyclin D1 and phosphorylated retinoblastoma protein decreased following treatment with arsenite, but this was not observed in BxPC-3 cells. To further examine the differences between these two cell lines, the effect of arsenite on upstream p44/p42 mitogen-activated protein kinase (MAPK) and Akt was investigated. PDGF-BB caused phosphorylation of p44/p42 MAPK and Akt in both cell lines. Pretreatment with arsenite significantly suppressed PDGF-BB-induced phosphorylation of Akt, but not of p44/p42 MAPK in AsPC-1 cells. By contrast, arsenite did not affect these molecules in BxPC-3 cells. Since the inhibition of the Akt signaling pathway markedly reduced PDGF-BB-induced migration in AsPC-1 cells, the present results strongly suggest that arsenite inhibits PDGF-BB-induced migration by suppressing the Akt signaling pathway in AsPC-1 cells. Therefore, arsenite may be a useful tool for the treatment of patients with certain types of pancreatic cancer, without causing adverse effects on normal pancreatic cells.

  15. Influence of biological soil crusts at different successional stages in the implantation of biogeochemical cycles in arid and semiarid zones

    Science.gov (United States)

    Gil-Sotres, F.; Miralles, I.; Canton-Castilla, Y.; Domingo, F.; Leiros, M. C.; Trasar-Cepeda, C.

    2012-04-01

    Influence of biological soil crusts at different successional stages in the implantation of biogeochemical cycles in arid and semiarid zones I. Miralles1, F. Gil-Sotres2, Y. Cantón-Castilla3, F. Domingo1, M.C. Leirós2, C. Trasar-Cepeda4 1 Experimental Estation of Arid Zones (CSIC), E-04230 La Cañada de San Urbano, Almería, Spain. 2 Departamento Edafología y Química Agrícola, Grupo de Evaluación de la Calidad del Suelo, Unidad Asociada CSIC, Facultad de Farmacia, Universidad de Santiago de Compostela, E-15782 Santiago de Compostela, Spain. 3 University of Almería, Departamento de Edafología y Química Agrícola, E-04230-La Cañada de San Urbano, Almería, Spain. 4 Departamento Bioquímica del Suelo, IIAG-CSIC, Apartado 122, E-15708 Santiago de Compostela, Spain. Crusts (BSCs) are formed by a close association between soil particles and cyanobacteria, algae, lichens, bryophytes and microfungi in varying proportions. Their habitat is within or immediately on top of the uppermost millimetres of the soil and are the predominant surface cover in arid and semiarid zones. Among the diverse functions developed by BSCs in the ecosystem (hydrology, erosion, soil properties, etc.), one of the most important is its role in nutrient cycling. Within arid and semiarid environments, BSCs have been termed 'mantles of fertility' being considered hotspots of biogeochemical inputs, fixing C, N and P above- and below-ground. However, there are differences in N and C fixation rates between BSCs types. Early successional BSCs, dominated by cyanobacterial species, fix lower quantities of C and N than mature BSCs dominated by lichens. Although the positive effects of BSCs on biogeochemical soil cycles are widely accepted, no previous studies have evaluated the activities of the enzymes involved in C, N and P cycles of BSCs and how they are affected by the successional stage of the BSC. In this work, performed in the Tabernas desert (SE Spain), we studied the hydrolase enzymes

  16. Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Valeria Gabriela Antico Arciuch

    Full Text Available Akt is a serine/threonine kinase involved in cell proliferation, apoptosis, and glucose metabolism. Akt is differentially activated by growth factors and oxidative stress by sequential phosphorylation of Ser(473 by mTORC2 and Thr(308 by PDK1. On these bases, we investigated the mechanistic connection of H(2O(2 yield, mitochondrial activation of Akt1 and cell cycle progression in NIH/3T3 cell line with confocal microscopy, in vivo imaging, and directed mutagenesis. We demonstrate that modulation by H(2O(2 entails the entrance of cytosolic P-Akt1 Ser(473 to mitochondria, where it is further phosphorylated at Thr(308 by constitutive PDK1. Phosphorylation of Thr(308 in mitochondria determines Akt1 passage to nuclei and triggers genomic post-translational mechanisms for cell proliferation. At high H(2O(2, Akt1-PDK1 association is disrupted and P-Akt1 Ser(473 accumulates in mitochondria in detriment to nuclear translocation; accordingly, Akt1 T308A is retained in mitochondria. Low Akt1 activity increases cytochrome c release to cytosol leading to apoptosis. As assessed by mass spectra, differential H(2O(2 effects on Akt1-PDK interaction depend on the selective oxidation of Cys(310 to sulfenic or cysteic acids. These results indicate that Akt1 intramitochondrial-cycling is central for redox modulation of cell fate.

  17. Relationship between the length of cell cycles, cleavage pattern and developmental competence in bovine embryos generated by in vitro fertilization or parthenogenesis.

    Science.gov (United States)

    Somfai, Tamás; Inaba, Yasushi; Aikawa, Yoshio; Ohtake, Masaki; Kobayashi, Shuji; Konishi, Kazuyuki; Imai, Kei

    2010-04-01

    This study was conducted to study the kinetics of initial cell divisions in relation with the cleavage patterns in viable (with the ability to develop to the blastocyst stage) and non-viable bovine embryos and parthenotes. The kinetics of in vitro development and cleavage patterns were observed by time lapse cinematography. The length of the first and second but not third cell cycle differed significantly between the viable and non-viable embryos after IVF or parthenogenesis. Viable embryos had significantly shorter first and second cell cycles than non-viable ones. The presence of fragments, protrusions and unequally-sized blastomeres was associated with an extended one-cell stage and reduced ability to develop to the blastocyst stage; however, the lengths of the second and third cell cycles were not altered. Oocytes showing direct division from one cell to 3 or 4 blastomeres showed similar developmental ability and embryonic cell numbers to those showing normal division, although, with a high frequency of chromosomal abnormalities. Our results suggest that the differences in the first cell cycles between viable and non-viable embryos were not sperm-related, whereas direct cleavage of 1-cell embryos to 3 or more blastomeres and protrusion formation are related to sperm-driven factors. The length of the first and second cell cycles and the cleavage pattern should be examined simultaneously to predict developmental competence of embryos at early cleavage stages. PMID:20035110

  18. IARS2 silencing induces non-small cell lung cancer cells proliferation inhibition, cell cycle arrest and promotes cell apoptosis.

    Science.gov (United States)

    Yin, J; Liu, W; Li, R; Liu, J; Zhang, Y; Tang, W; Wang, K

    2016-01-01

    The purpose of this study was to investigate the potential role of Ileucyl-tRNA synthetase (IARS2) silencing in non-small cell lung cancer (NSCLC). The silencing of IARS2 in H1299 cells and A549 cells were performed by lentivirus encoding shRNAs. The efficiency of IARS2 silencing was detected by quantitative real time PCR and western blot. The effects of IARS2 silencing on cell growth, cell apoptosis, cell cycle and cell colony formation ability were assessed by cells counting, MTT assay, flow cytometer analysis and soft agar colony formation assay, respectively. Compared with negative control group, IARS2 was significantly knockdown by transfection with lentivirus encoding shRNA of IARS2. The IARS2 silencing significantly inhibited the cells proliferation and cells colony formation ability, induced cell cycle arrest at G1/S phase and promoted cell apoptosis. IARS2 silencing induced NSCLC cells growth inhibition, cell cycle arrest and promoted cell apoptosis. These results suggest that IARS2 may be a novel target for the treatment of NSCLC. PMID:26639235

  19. Female germ cell renewal during the annual reproductive cycle in Ostariophysians fish.

    Science.gov (United States)

    Wildner, Daniel Dantas; Grier, Harry; Quagio-Grassiotto, Irani

    2013-03-01

    The objective was to characterize female germ cell renewal during the annual reproductive cycle in two species of ostariophysian fish with distinct reproductive strategies: a siluriform, Pimelodus maculatus, in which oocyte development is group synchronous and the annual reproductive period is short; and a characiform, Serrasalmus maculatus, with asynchronous oocyte development and a prolonged reproductive period. These reproductive strategies result in fish determinate and indeterminate fecundity, respectively. Annual reproductive phases were determined by biometric and histologic analysis of gonads and interpreted according to new proposals for phase classification and stages of oocyte development (with special attention to germinal epithelium activity). Histologically, there were two types of oogonia in the germinal epithelium: single oogonia and those in mitotic proliferation. Oogonial proliferation and their entry into meiosis resulted in formation of cell nests (clusters of cells in the ovarian lamellae). Morphometric analysis was used to estimate germ cell renewal. Based on numbers of single oogonia in the lamellar epithelium, and nests with proliferating oogonia or early prophase oocytes throughout the annual reproductive cycle, oogonial proliferation and entrance into meiosis were more intense during the regenerating phase and developing phase, but decreased sharply (P < 0.05) during the spawning-capable phase. Oogonial proliferation gradually recovered during the regressing phase. We concluded that, independent of species or features of the reproductive cycle, germ cell renewal occurred during the regenerating phase, ensuring availability of eggs for the spawning event. PMID:23317762

  20. SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells.

    Science.gov (United States)

    Bonifati, Serena; Daly, Michele B; St Gelais, Corine; Kim, Sun Hee; Hollenbaugh, Joseph A; Shepard, Caitlin; Kennedy, Edward M; Kim, Dong-Hyun; Schinazi, Raymond F; Kim, Baek; Wu, Li

    2016-08-01

    SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G1/G0 phase and reduces apoptosis. These alterations correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection. PMID:27183329

  1. Cell cycle and DNA repair in UV-irradiated cells of mouse neuroblastoma

    International Nuclear Information System (INIS)

    A correlation has been shown between a reduced rate of movement of UV-irradiated neuroblastoma cells from G1 into S phase, an essential increase of cells in S phase while progressing through the cell cycle, and a defect in free DNA synthesis on a damaged template. These indices may reflect one and the same cell response to the UV light

  2. The Result of Combined Modality Treatment for Limited Stage Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    From July 1984 to September 1988, 27 patients with limited stage small cell lung cancer were treated with combined modality(combination chemotherapy Plus radiotherapy) at the Department of Therapeutic Radiology in Kyungpook National University Hospital. Of the 27 patients, 19(70%) achieved a complete response, 6(22%) a partial response, and 2(8%) no response. Female, performance status HO, serum enolase level below 30ng/ml, radiation dose over 4500 cGy, and 4 or more cycles of chemotherapy had a favorable effect on the rates of complete response, although there were no statistical differences according to the variables. Median survival time was 10 Months and overall 1- and 2-year survival rates were 40.7% and 12.2%, respectively. Complete response(p<0.05), performance status HO(p<0.05), 4 or more cycles of chemotherapy(p<0.05), and radiation dose over 4500 cGy had a significantly favorable effect on 2-year survival rate. Prophylactic cranial irradiation or sex had no effect on survival. The results of this study suggest that radiation treatment should be combined with combination chemotherapy in the therapeutic strategy of SCLC of limited stage

  3. POST-OPERATIVE STAGING AND SURVIVAL BASED ON THE REVISED TNM STAGING SYSTEM FOR NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the factors affecting post-operative staging and survival in non-small cell lung cancer (NSCLC) patients based on the revised TNM staging system adopted by the UICC in 1977. Methods: Data were collected from 1757 consecutively operated NSCLC patients, including those receiving complete tumor excision, tumor debulking and exploratory thoractomy from April 1969 through Dec. 1993. the end point of follow-up was Nov. 30, 1998. Cumulative survival and its influencing factors were analyzed by Kaplan-Meier and Cox model of SPSS software. Results: In this series, 30 patients (1.7%) were lost from follow-up. The 5-year cumulative survival was 88.0% for patients in stage I A, and 53.9% in stage IB, 33.5% in stage II, 14.7% in stage IIIA, 5.5% in stage IIIB and 7.0% in stage IV. The overall 5-year survival rate was 28.2%. The 5-year survivals were 39.8%, 14.4% and 4.2% in patients treated with completely tumor resection, tumor debulking and explorative thoractomy, respectively. The 10-year survival rate was 31.4%, 9.5% and 0, respectively. Factors affecting long-term cumulative survival, in the order of decreasing significance, were the type of operation, lymph node status, staging, size and pathological type of the primary tumor. Conclusion: the revised staging system for NSCLC is superior to that used since 1986 as far as the end results of treatment in patients in different stage and the staging specificity are concerned. The T3N1M0 classification and the definition of M1 need to be further studied.

  4. The improvement of approaches to marketing testing of ecological innovative products in the stages of innovative cycle

    Directory of Open Access Journals (Sweden)

    Ye.I. Nagornyi

    2013-12-01

    Full Text Available The aim of the article. The aim of the article is theoretical justification and improvement of approaches to marketing testing of ecological innovative production in the stages of innovative cycle, and the sequence of decision-making procedures on its readiness to entry into the market by results of testing. The results of the analysis. Launch of the ecological innovative products on the market and providing its passage through the stages of the innovative cycle requires continuous and high-quality information and analytical support. This support can be reached as a result of marketing testing procedures. The analysis of the existing evolutionary approaches to marketing testing procedure allowed finding out that they are not deprived disadvantages. Separate theoretical and methodological aspects of marketing testing of innovative products are analyzed in the scientific literature. But issues of marketing testing of ecological innovations and introduction of the given procedure at early stages of an innovative cycle are insufficiently investigated. Author's definition of marketing testing concept is reduced to complex process of a choice, an assessment and selection of a subject of the marketing approbation which is carried out at each stage of product development, for stage-by-stage and general definition of progress level of innovative production in the market, and also for the analysis of its readiness degree to entry the market. As a subject of approbation can be used: directions of innovative development of the enterprise, sources of ideas, ideas, concepts, prototypes of new products and their market attributes, and also marketing strategy as a whole. The types of testing taking place at each stage of an innovative cycle of development of goods are allocated in research. Problems (tasks that procedure of marketing testing solves are researched and methodological approaches to its implementation are suggested. Marketing testing is a complex

  5. Polyamines and the Cell Cycle of Catharanthus roseus Cells in Culture 1

    Science.gov (United States)

    Maki, Hisae; Ando, Satoshi; Kodama, Hiroaki; Komamine, Atsushi

    1991-01-01

    Investigation was made on the effect of partial depletion of polyamines (PAs), induced by treatment with inhibitors of the biosynthesis of PAs, on the distribution of cells at each phase of the cell cycle in Catharanthus roseus (L.) G. Don. cells in suspension cultures, using flow cytometry. More cells treated with inhibitors of arginine decarboxylase (ADC) and ornithine decarboxylase (ODC) were accumulated in the G1 phase than those in the control, while the treatment with an inhibitor of spermidine (SPD) synthase showed no effect on the distribution of cells. The endogenous levels of the PAs, putrescine (PUT), SPD, and spermine (SPM), were determined during the cell cycle in synchronous cultures of C. roseus. Two peaks of endogenous level of PAs, in particular, of PUT and SPD, were observed during the cell cycle. Levels of PAs increased markedly prior to synthesis of DNA in the S phase and prior to cytokinesis. Activities of ADC and ODC were also assayed during the cell cycle. Activities of ADC was much higher than that of ODC throughout the cell cycle, but both activities of ODC and ADC changed in concert with changes in levels of PAs. Therefore, it is suggested that these enzymes may regulate PA levels during the cell cycle. These results indicate that inhibitors of PUT biosynthesis caused the suppression of cell proliferation by prevention of the progression of the cell cycle, probably from the G1 to the S phase, and PUT may play more important roles in the progression of the cell cycle than other PAs. PMID:16668290

  6. Clinical variants, stages, and management of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Lyubomir A Dourmishev

    2013-01-01

    Full Text Available Basal cell carcinoma (BCC is the most common paraneoplastic disease among human neoplasms. The tumor affects mainly photoexposed areas, most often in the head and seldom appears on genitalia and perigenital region. BCC progresses slowly and metastases are found in less than 0.5% of the cases; however, a considerable local destruction and mutilation could be observed when treatment is neglected or inadequate. Different variants as nodular, cystic, micronodular, superficial, pigment BCC are described in literature and the differential diagnosis in some cases could be difficult. The staging of BCC is made according to Tumor, Node, Metastasis (TNM classification and is essential for performing the adequate treatment. Numerous therapeutic methods established for treatment of BCC, having their advantages or disadvantages, do not absolutely dissolve the risk of relapses. The early diagnostics based on the good knowledge and timely organized and adequate treatment is a precondition for better prognosis. Despite the slow progress and numerous therapeutic methods, the basal cell carcinoma should not be underestimated.

  7. Lineage-specific interface proteins match up the cell cycle and differentiation in embryo stem cells

    DEFF Research Database (Denmark)

    Re, Angela; Workman, Christopher; Waldron, Levi;

    2014-01-01

    The shortage of molecular information on cell cycle changes along embryonic stem cell (ESC) differentiation prompts an in silico approach, which may provide a novel way to identify candidate genes or mechanisms acting in coordinating the two programs. We analyzed germ layer specific gene expression...... changes during the cell cycle and ESC differentiation by combining four human cell cycle transcriptome profiles with thirteen in vitro human ESC differentiation studies. To detect cross-talk mechanisms we then integrated the transcriptome data that displayed differential regulation with protein...... interaction data. A new class of non-transcriptionally regulated genes was identified, encoding proteins which interact systematically with proteins corresponding to genes regulated during the cell cycle or cell differentiation, and which therefore can be seen as interface proteins coordinating the two...

  8. Direct inhibition of Retinoblastoma phosphorylation by Nimbolide causes cell cycle arrest and suppresses glioblastoma growth

    Science.gov (United States)

    Anderson, Jane; Liu, Xiaona; Henry, Heather; Gasilina, Anjelika; Nassar, Nicholas; Ghosh, Jayeeta; Clark, Jason P; Kumar, Ashish; Pauletti, Giovanni M.; Ghosh, Pradip K; Dasgupta, Biplab

    2013-01-01

    Purpose Classical pharmacology allows the use and development of conventional phytomedicine faster and more economically than conventional drugs. This approach should be tested for their efficacy in terms of complementarity and disease control. The purpose of this study was to determine the molecular mechanisms by which nimbolide, a triterpenoid found in the well-known medicinal plant Azadirachta indica controls glioblastoma (GBM) growth. Experimental Design Using in vitro signaling, anchorage-independent growth, kinase assays, and xenograft models, we investigated the mechanisms of its growth inhibition in glioblastoma. Results We show that nimbolide or an ethanol soluble fraction of A. indica leaves (Azt) that contains nimbolide as the principal cytotoxic agent is highly cytotoxic against GBM in vitro and in vivo. Azt caused cell cycle arrest, most prominently at the G1-S stage in GBM cells expressing EGFRvIII, an oncogene present in about 20-25% of GBMs. Azt/nimbolide directly inhibited CDK4/CDK6 kinase activity leading to hypophosphorylation of the retinoblastoma (RB) protein, cell cycle arrest at G1-S and cell death. Independent of RB hypophosphorylation, Azt also significantly reduced proliferative and survival advantage of GBM cells in vitro and in tumor xenografts by downregulating Bcl2 and blocking growth factor induced phosphorylation of Akt, Erk1/2 and STAT3. These effects were specific since Azt did not affect mTOR or other cell cycle regulators. In vivo, Azt completely prevented initiation and inhibited progression of GBM growth. Conclusions Our preclinical findings demonstrate Nimbolide as a potent anti-glioma agent that blocks cell cycle and inhibits glioma growth in vitro and in vivo. PMID:24170547

  9. DETERMINATION OF MAIN OUTPUT PARAMETERS FOR HYDROFICATED CONSTRUCTION AND ROAD-BUILDING MACHINES AT OPERATIONAL STAGE OF THEIR LIFE CYCLE

    Directory of Open Access Journals (Sweden)

    A. N. Maximenko

    2015-01-01

    Full Text Available Usage efficiency of mechanical engineering products is determined by level of their operating capability. Expenses connected with provision of operating capability for the whole operational period exceed initial cost of the products by 6-10-fold. Moreover , while being used the expenses have a tendency to increase with reduction of output parameters that ensure product application efficiency for its intended purpose. It is necessary to take into account these changes at manufacturing stages of mechanical engineering products. Maximum efficiency can be obtained at the operational stage of the product life cycle only as a result of complex and interrelated measures during designing, manufacturing and usage of the specific product for its intended purpose with due account of its output parameter dynamics. While using the product an analysis of its output parameter dynamics will make it possible to determine maximum value of the operating capability, operational expenses and best practices for obtaining maximum profit per operating time unit.Taking hydroficated excavators of the 5th grade as an example the paper presents dynamics of main output parameters at the operational stage of their life cycle; reveals the main factor influencing on intensity of hydroficated machine operating capability reduction; substantiates an expediency of taking into account output parameter dynamics while evaluating efficiency of its usage; proposes a methodology for determination of or a pay-off time period for recoupment of expenses pertaining to machine procurement and optimum time period for operational stage, its life cycle that corresponds to obtaining maximum profit.Nowadays constant values of main output parameters (operating capability, self cost of machine-hour corresponding to the beginning of operation are to be taken into account while determining expediency of machine creation. Practically they significantly change in the process of machine operation this

  10. Morphometry and morphology of nucleus of the Sertoli and interstitial cells of the tambaqui Colossoma macropomum (Cuvier, 1881) (Pisces: Characidae) during the reproductive cycle

    OpenAIRE

    Nakaghi L. S. O.; Mitsuiki D.; Santos H. S. L.; Pacheco M. R.; Ganeco L. N.

    2003-01-01

    This study allowed the characterization of the tambaqui Colossoma macropomum testes structural organization, emphasizing Sertoli and interstitial cells and analyzing morphometrically the Sertoli cell nucleus diameter and the interstitial tissue area during the reproductive cycle. Fragments of tambaqui testes were collected in the following reproductive cycle stages: immature, resting, maturation I and II, mature, and regression, and were histologically processed. The Sertoli cells were found ...

  11. Plant characteristics of an integrated solid oxide fuel cell cycle and a steam cycle

    International Nuclear Information System (INIS)

    Plant characteristics of a system containing a solid oxide fuel cell (SOFC) cycle on the top of a Rankine cycle were investigated. A desulfurization reactor removes the sulfur content in the fuel, while a pre-reformer broke down the heavier hydrocarbons in an adiabatic steam reformer (ASR). The pre-treated fuel then entered to the anode side of the SOFC. The remaining fuels after the SOFC stacks entered a catalytic burner for further combusting. The burned gases from the burner were then used to produce steam for the Rankine cycle in a heat recovery steam generator (HRSG). The remaining energy of the off-gases was recycled back to the topping cycle for further utilization. Several parameter studies were carried out to investigate the sensitivity of the suggested plant. It was shown that the operation temperature of the desulfurization and the pre-reformer had no effect on the plant efficiency, which was also true when decreasing the anode temperature. However, increasing the cathode temperature had a significant effect on the plant efficiency. In addition, decreasing the SOFC utilization factor from 0.8 to 0.7, increases the plant efficiency by about 6%. An optimal plant efficiency of about 71% was achieved by optimizing the plant.

  12. Regulatory mechanism of radiation-induced cancer cell death by the change of cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Soo Jin; Jeong, Min Ho; Jang, Ji Yeon [College of Medicine, Donga Univ., Pusan (Korea, Republic of)

    2003-09-01

    In our previous study, we have shown the main cell death pattern induced by irradiation or protein tyrosine kinase (PTK) inhibitors in K562 human myelogenous leukemic cell line. Death of the cells treated with irradiation alone was characterized by mitotic catastrophe and typical radiation-induced apoptosis was accelerated by herbimycin A (HMA). Both types of cell death were inhibited by genistein. In this study, we investigated the effects of HMA and genistein on cell cycle regulation and its correlation with the alterations of radiation-induced cell death. K562 cells in exponential growth phase were used for this study. The cells were irradiated with 10 Gy using 6 MeV Linac (200-300 cGy/min). Immediately after irradiation, cells were treated with 250 nM of HMA or 25{mu}M of genistein. The distributions of cell cycle, the expressions of cell cycle-related protein, the activities of cyclin-dependent kinase, and the yield of senescence and differentiation were analyzed. X-irradiated cells were arrested in the G2 phase of the cell cycle but unlike the p53-positive cells, they were not able to sustain the cell cycle arrest. An accumulation of cells in G2 phase of first cell-cycle post-treatment and an increase of cyclin B1 were correlated with spontaneous, premature, chromosome condensation and mitotic catastrophe. HMA induced rapid G2 checkpoint abrogation and concomitant p53-independent G1 accumulation HMA-induced cell cycle modifications correlated with the increase of cdc2 kinase activity, the decrease of the expressions of cyclins E and A and of CDK2 kinase activity, and the enhancement of radiation-induced apoptosis. Genistein maintained cells that were arrested in the G2-phase, decreased the expressions of cyclin B1 and cdc25C and cdc2 kinase activity, increased the expression of p16, and sustained senescence and megakaryocytic differentiation. The effects of HMA and genistein on the radiation-induced cell death of K562 cells were closely related to the cell

  13. The Structure of Stages in the Evaluation Cycle: An Event Sequence Analysis.

    Science.gov (United States)

    Wilson, Clarke

    2000-01-01

    Describes the tasks undertaken in the cycle of evaluation of housing programs by the Canada Mortgage and Housing Corporation prior to 1997 and analyzes the major evaluation projects in terms of the similarity of constituent tasks. Introduces combinatorial methods and new research applications. (SLD)

  14. Differential regulation of survivin by p53 contributes to cell cycle dependent apoptosis

    Institute of Scientific and Technical Information of China (English)

    Yan JIN; Yong WEI; Lei XIONG; Ying YANG; Jia Rui WU

    2005-01-01

    Recent studies indicate that cell-cycle checkpoints are tightly correlated with the regulation of apoptosis, in which p53 plays an important role. Our present works show that the expression of E6/E7 oncogenes of human papillomavirus in HeLa cells is inhibited in the presence of anti-tumor reagent tripchlorolide (TC), which results in the up-regulation of p53 in HeLa cells. Interestingly, under the same TC-treatment, the cells at the early S-phase are more susceptible to apoptosis than those at the middle S-phase although p53 protein is stabilized to the same level in both situations.Significant difference is exhibited between the two specified expression profiles. Further analysis demonstrates that anti-apoptotic gene survivin is up-regulated by p53 in the TC-treated middle-S cells, whereas it is down-regulated by p53 in the TC-treated early-S cells. Taken together, the present study indicates that the differential p53-regulated expression of survivin at different stages of the cell cycle results in different cellular outputs under the same apoptosis-inducer.

  15. Ovarian Follicular Fluid Constituents in Relation to Stage of Estrus Cycle and Size of the Follicle in Buffalo

    Directory of Open Access Journals (Sweden)

    Hussein H. A.

    2010-12-01

    Full Text Available The goal of the present study was to evaluate the difference in constituent of the ovarian follicular fluid in different stages of the estrus cycle and in medium and large sized follicle and also to evaluate the relation between serum and follicular fluid constituents in cyclic buffalos. A total of 34 clinically healthy buffalo (Bubals bubals, aged 7-10 years, were sent for slaughter in Moesha Abattoir, Assiut province in winter 2009. Blood samples and the whole genital tract of each animal were collected. The stage of the cycle (proestrus n= 8, estrus n= 7, metestrus n= 7 and diestrus n= 12 was determined post mortem. Biochemical analysis of serum and follicular fluid was performed through measuring total protein, albumin, chloride, potassium, phosphorus, magnesium, glucose, cholesterol, triglyceride, urea, creatinine levels and lactate dehydrogenase (LDH activity. Results of the present study revealed that during the estrus cycle, only follicular triglyceride, urea, creatinine and phosphorus level showed significant changes. A positive correlation was found between follicular albumin, phosphorus levels and follicular diameter. Total protein, albumin, globulins, glucose, chloride and creatinine were significantly higher in the serum than that in the follicular fluid. Follicular triglyceride level and potassium level were significantly higher than serum level. Follicular LDH activity was higher in large sized follicle than small sized one. Further studies are required to elucidate the relation between concentration of urea and creatinine in the follicular fluid and oocyte viability. [Vet. World 2010; 3(6.000: 263-267

  16. Systematic identification of yeast cell cycle transcription factors using multiple data sources

    Directory of Open Access Journals (Sweden)

    Li Wen-Hsiung

    2008-12-01

    Full Text Available Abstract Background Eukaryotic cell cycle is a complex process and is precisely regulated at many levels. Many genes specific to the cell cycle are regulated transcriptionally and are expressed just before they are needed. To understand the cell cycle process, it is important to identify the cell cycle transcription factors (TFs that regulate the expression of cell cycle-regulated genes. Results We developed a method to identify cell cycle TFs in yeast by integrating current ChIP-chip, mutant, transcription factor binding site (TFBS, and cell cycle gene expression data. We identified 17 cell cycle TFs, 12 of which are known cell cycle TFs, while the remaining five (Ash1, Rlm1, Ste12, Stp1, Tec1 are putative novel cell cycle TFs. For each cell cycle TF, we assigned specific cell cycle phases in which the TF functions and identified the time lag for the TF to exert regulatory effects on its target genes. We also identified 178 novel cell cycle-regulated genes, among which 59 have unknown functions, but they may now be annotated as cell cycle-regulated genes. Most of our predictions are supported by previous experimental or computational studies. Furthermore, a high confidence TF-gene regulatory matrix is derived as a byproduct of our method. Each TF-gene regulatory relationship in this matrix is supported by at least three data sources: gene expression, TFBS, and ChIP-chip or/and mutant data. We show that our method performs better than four existing methods for identifying yeast cell cycle TFs. Finally, an application of our method to different cell cycle gene expression datasets suggests that our method is robust. Conclusion Our method is effective for identifying yeast cell cycle TFs and cell cycle-regulated genes. Many of our predictions are validated by the literature. Our study shows that integrating multiple data sources is a powerful approach to studying complex biological systems.

  17. Cell Cycle Analysis of CML Stem Cells Using Hoechst 33342 and Propidium Iodide.

    Science.gov (United States)

    DeSouza, Ngoc; Zhou, Megan; Shan, Yi

    2016-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disease with an expansion of white blood cells. The current treatments for CML are shown not to be long-term effective because of CML stem cells' insensitivity to tyrosine kinase inhibitors. Therefore, studying more about CML stem cells is essential to understand the pathways of CML stem cell development and proliferation and finally lead to effective treatments to eliminate CML stem cells and eradicate CML. This chapter describes two methods to analyze cell cycle of CML stem cells. The rare population of CML stem cells can be identified by staining with cell surface markers, and then DNA-binding dyes Hoechst 33342 and propidium iodide (PI) are added to stain the DNA content which is changed when cells go through different phases of the cell cycle. Samples are run through the flow cytometer to be analyzed based on different absorbance and emission wavelengths of different florescent colors. PMID:27581138

  18. Stage of Family Life Cycle, Ego Development, and the Marriage Relationship.

    Science.gov (United States)

    Swensen, Clifford H.; And Others

    1981-01-01

    Examined the marriage relationship in relation to the personality of the partners and the context within which the relationship exists. Results indicated that both the amount of love expressed and the amount of marriage problems declined from the first stages of marriage to the last. (Author/RC)

  19. Implementation of Life Cycle Assessment (LCA) in the early stages of product development

    DEFF Research Database (Denmark)

    Bhander, Gurbakhash Singh; Hauschild, Michael Zwicky; McAloone, Timothy Charles

    2003-01-01

    The paper aims to outline the problems for the designer in evaluating the environmental benignity of the product from the outset and to provide the designer with a framework for decision support based on the performance evaluation at different stages of the design process. The overall aim of the ...

  20. Thermodynamic Analysis of an Integrated Solid Oxide Fuel Cell Cycle with a Rankine Cycle

    DEFF Research Database (Denmark)

    Rokni, Masoud

    2010-01-01

    enters then into the anode side of the SOFC. The remaining fuels after the SOFC stacks enter a burner for further burning. The off-gases are then used to produce steam for a Rankine cycle in a Heat Recovery Steam Generator (HRSG). Different system setups are suggested. Cyclic efficiencies up to 67% are......Hybrid systems consisting of Solid Oxide Fuel Cells (SOFC) on the top of a Steam Turbine (ST) are investigated. The plants are fired by natural gas (NG). A desulfurization reactor removes the sulfur content in the fuel while a pre-reformer breaks down the heavier hydrocarbons. The pre-treated fuel...... achieved which is considerably higher than the conventional Combined Cycles (CC). Both ASR (Adiabatic Steam Reformer) and CPO (Catalytic Partial Oxidation) fuel pre-reformer reactors are considered in this investigation....

  1. Cell cycle arrest induced by MPPa-PDT in MDA-MB-231 cells

    Science.gov (United States)

    Liang, Liming; Bi, Wenxiang; Tian, Yuanyuan

    2016-05-01

    Photodynamic therapy (PDT) is a medical treatment using a photosensitizing agent and light source to treat cancers. Pyropheophorbidea methyl ester (MPPa), a derivative of chlorophyll, is a novel potent photosensitizer. To learn more about this photosensitizer, we examined the cell cycle arrest in MDA-MB-231. Cell cycle and apoptosis were measured by flow cytometer. Checkpoints of the cell cycle were measured by western blot. In this study, we found that the expression of Cyclin D1 was obviously decreased, while the expression of Chk2 and P21 was increased after PDT treatment. This study showed that MPPa-PDT affected the checkpoints of the cell cycle and led the cells to apoptosis.

  2. Modulation of cell cycle control during oocyte-to-embryo transitions

    Science.gov (United States)

    Hörmanseder, Eva; Tischer, Thomas; Mayer, Thomas U

    2013-01-01

    Ex ovo omnia—all animals come from eggs—this statement made in 1651 by the English physician William Harvey marks a seminal break with the doctrine that all essential characteristics of offspring are contributed by their fathers, while mothers contribute only a material substrate. More than 360 years later, we now have a comprehensive understanding of how haploid gametes are generated during meiosis to allow the formation of diploid offspring when sperm and egg cells fuse. In most species, immature oocytes are arrested in prophase I and this arrest is maintained for few days (fruit flies) or for decades (humans). After completion of the first meiotic division, most vertebrate eggs arrest again at metaphase of meiosis II. Upon fertilization, this second meiotic arrest point is released and embryos enter highly specialized early embryonic divisions. In this review, we discuss how the standard somatic cell cycle is modulated to meet the specific requirements of different developmental stages. Specifically, we focus on cell cycle regulation in mature vertebrate eggs arrested at metaphase II (MII-arrest), the first mitotic cell cycle, and early embryonic divisions. PMID:23892458

  3. Host Cell Autophagy Modulates Early Stages of Adenovirus Infections in Airway Epithelial Cells

    OpenAIRE

    Zeng, Xuehuo; Carlin, Cathleen R

    2013-01-01

    Human adenoviruses typically cause mild infections in the upper or lower respiratory tract, gastrointestinal tract, or ocular epithelium. However, adenoviruses may be life-threatening in patients with impaired immunity and some serotypes cause epidemic outbreaks. Attachment to host cell receptors activates cell signaling and virus uptake by endocytosis. At present, it is unclear how vital cellular homeostatic mechanisms affect these early steps in the adenovirus life cycle. Autophagy is a lys...

  4. The circadian clock and cell cycle: Interconnected biological circuits

    OpenAIRE

    Masri, Selma; Cervantes, Marlene; Sassone-Corsi, Paolo

    2013-01-01

    The circadian clock governs biological timekeeping on a systemic level, helping to regulate and maintain physiological processes, including endocrine and metabolic pathways with a periodicity of 24-hours. Disruption within the circadian clock machinery has been linked to numerous pathological conditions, including cancer, suggesting that clock-dependent regulation of the cell cycle is an essential control mechanism. This review will highlight recent advances on the ‘gating’ controls of the ci...

  5. Cdk Activity Couples Epigenetic Centromere Inheritance to Cell Cycle Progression

    OpenAIRE

    Silva, Mariana C.C.; Bodor, Dani L.; Stellfox, Madison E.; Martins, Nuno M.C.; Hochegger, Helfrid; Foltz, Daniel R.; Jansen, Lars E.T.

    2012-01-01

    Centromeres form the site of chromosome attachment to microtubules during mitosis. Identity of these loci is maintained epigenetically by nucleosomes containing the histone H3 variant CENP-A. Propagation of CENP-A chromatin is uncoupled from DNA replication initiating only during mitotic exit. We now demonstrate that inhibition of Cdk1 and Cdk2 activities is sufficient to trigger CENP-A assembly throughout the cell cycle in a manner dependent on the canonical CENP-A assembly machinery. We fur...

  6. The Cell Cycle Timing of Human Papillomavirus DNA Replication.

    Science.gov (United States)

    Reinson, Tormi; Henno, Liisi; Toots, Mart; Ustav, Mart; Ustav, Mart

    2015-01-01

    Viruses manipulate the cell cycle of the host cell to optimize conditions for more efficient viral genome replication. One strategy utilized by DNA viruses is to replicate their genomes non-concurrently with the host genome; in this case, the viral genome is amplified outside S phase. This phenomenon has also been described for human papillomavirus (HPV) vegetative genome replication, which occurs in G2-arrested cells; however, the precise timing of viral DNA replication during initial and stable replication phases has not been studied. We developed a new method to quantitate newly synthesized DNA levels and used this method in combination with cell cycle synchronization to show that viral DNA replication is initiated during S phase and is extended to G2 during initial amplification but follows the replication pattern of cellular DNA during S phase in the stable maintenance phase. E1 and E2 protein overexpression changes the replication time from S only to both the S and G2 phases in cells that stably maintain viral episomes. These data demonstrate that the active synthesis and replication of the HPV genome are extended into the G2 phase to amplify its copy number and the duration of HPV genome replication is controlled by the level of the viral replication proteins E1 and E2. Using the G2 phase for genome amplification may be an important adaptation that allows exploitation of changing cellular conditions during cell cycle progression. We also describe a new method to quantify newly synthesized viral DNA levels and discuss its benefits for HPV research. PMID:26132923

  7. The Cell Cycle Timing of Human Papillomavirus DNA Replication.

    Directory of Open Access Journals (Sweden)

    Tormi Reinson

    Full Text Available Viruses manipulate the cell cycle of the host cell to optimize conditions for more efficient viral genome replication. One strategy utilized by DNA viruses is to replicate their genomes non-concurrently with the host genome; in this case, the viral genome is amplified outside S phase. This phenomenon has also been described for human papillomavirus (HPV vegetative genome replication, which occurs in G2-arrested cells; however, the precise timing of viral DNA replication during initial and stable replication phases has not been studied. We developed a new method to quantitate newly synthesized DNA levels and used this method in combination with cell cycle synchronization to show that viral DNA replication is initiated during S phase and is extended to G2 during initial amplification but follows the replication pattern of cellular DNA during S phase in the stable maintenance phase. E1 and E2 protein overexpression changes the replication time from S only to both the S and G2 phases in cells that stably maintain viral episomes. These data demonstrate that the active synthesis and replication of the HPV genome are extended into the G2 phase to amplify its copy number and the duration of HPV genome replication is controlled by the level of the viral replication proteins E1 and E2. Using the G2 phase for genome amplification may be an important adaptation that allows exploitation of changing cellular conditions during cell cycle progression. We also describe a new method to quantify newly synthesized viral DNA levels and discuss its benefits for HPV research.

  8. TRICHOSTATIN A INHIBITS PROLIFERATION, INDUCES APOPTOSIS AND CELL CYCLE ARREST IN HELA CELLS

    Institute of Scientific and Technical Information of China (English)

    XU Zhou-min; WANG Yi-qun; MEI Qi; CHEN Jian; DU Jia; WEI Yan; XU Ying-chun

    2006-01-01

    Objective: The histone deacetylase inhibitors (HDACIS) have been shown to inhibit cancer cell proliferation, stimulate apoptosis, an induce cell cycle arrest. Our purpose was to investigate the antiproliferative effects of a HDACI, trichostatin A (TSA), against human cervical cancer cells (HeLa). Methods: HeLa cells were treated in vitro with various concentrations of TSA. The inhibitory effect of TSA on the growth of HeLa cells was measured by MTT assay. To detect the characteristic of apoptosis chromatin condensation, HeLa cells were stained with Hoechst 33258 in the presence of TSA. Induction of cell cycle arrest was studied by flow cytometry. Changes in gene expression of p53, p21Waf1 and p27Kip1 were studied by semiquantitative RT-PCR. Results: TSA inhibited cell growth in a time- and dose-dependent manner. Hoechst 33258 staining assay showed that TSA induced apoptosis. Cell cycle analysis indicated that treatment with TSA decreased the proportion of cells in S phase and increased the proportion of cells in G0/G1 and/or G2/M phases of the cell cycle. This was concomitant with overexpression of genes related to malignant phenotype, including an increase in p53, p21Waf1 and p27Kip1. Conclusion: These results suggest that TSA is effective in inhibiting growth of HeLa cells in vitro. The findings raise the possibility that TSA may prove particularly effective in treatment of cervical cancers.

  9. Functional dissection of Caenorhabditis elegans CLK-2/TEL2 cell cycle defects during embryogenesis and germline development.

    Directory of Open Access Journals (Sweden)

    Sandra C Moser

    2009-04-01

    Full Text Available CLK-2/TEL2 is essential for viability from yeasts to vertebrates, but its essential functions remain ill defined. CLK-2/TEL2 was initially implicated in telomere length regulation in budding yeast, but work in Caenorhabditis elegans has uncovered a function in DNA damage response signalling. Subsequently, DNA damage signalling defects associated with CLK-2/TEL2 have been confirmed in yeast and human cells. The CLK-2/TEL2 interaction with the ATM and ATR DNA damage sensor kinases and its requirement for their stability led to the proposal that CLK-2/TEL2 mutants might phenocopy ATM and/or ATR depletion. We use C. elegans to dissect developmental and cell cycle related roles of CLK-2. Temperature sensitive (ts clk-2 mutants accumulate genomic instability and show a delay of embryonic cell cycle timing. This delay partially depends on the worm p53 homolog CEP-1 and is rescued by co-depletion of the DNA replication checkpoint proteins ATL-1 (C. elegans ATR and CHK-1. In addition, clk-2 ts mutants show a spindle orientation defect in the eight cell stages that lead to major cell fate transitions. clk-2 deletion worms progress through embryogenesis and larval development by maternal rescue but become sterile and halt germ cell cycle progression. Unlike ATL-1 depleted germ cells, clk-2-null germ cells do not accumulate DNA double-strand breaks. Rather, clk-2 mutant germ cells arrest with duplicated centrosomes but without mitotic spindles in an early prophase like stage. This germ cell cycle arrest does not depend on cep-1, the DNA replication, or the spindle checkpoint. Our analysis shows that CLK-2 depletion does not phenocopy PIKK kinase depletion. Rather, we implicate CLK-2 in multiple developmental and cell cycle related processes and show that CLK-2 and ATR have antagonising functions during early C. elegans embryonic development.

  10. Soaking RNAi in Bombyx mori BmN4-SID1 cells arrests cell cycle progression.

    Science.gov (United States)

    Mon, Hiroaki; Li, Zhiqing; Kobayashi, Isao; Tomita, Shuichiro; Lee, JaeMan; Sezutsu, Hideki; Tamura, Toshiki; Kusakabe, Takahiro

    2013-01-01

    RNA interference (RNAi) is an evolutionarily conserved mechanism for sequence-specific gene silencing. Previously, the BmN4-SID1 cell expressing Caenorhabditis ele gans SID-1 was established, in which soaking RNAi could induce effective gene silencing. To establish its utility, 6 cell cycle progression related cDNAs, CDK1, MYC, MYB, RNRS, CDT1, and GEMININ, were isolated from the silkworm, Bombyx mori L. (Lepidoptera: Bombycidae), and their expressions were further silenced by soaking RNAi in the BmN4-SID1 cells. The cell cycle progression analysis using flow cytometer demonstrated that the small amount of double stranded RNA was enough to arrest cell cycle progression at the specific cell phases. These data suggest that RNAi in the BmN4-SID1 cells can be used as a powerful tool for loss-of-function analysis of B. mori genes. PMID:24773378

  11. THE EFFICIENCY OF PROMOTIONAL INSTRUMENTS RELATED TO THE PRODUCT LIFE CYCLE STAGES

    OpenAIRE

    MIHAELA MARCU; CRISTINA GHERMAN

    2010-01-01

    Regarded as a planning tool, PLC (product life cycle) strongly contributes to the identification of the main marketing challenges that may arise throughout the life of a product/service. Thus, the marketing management has the opportunity to develop and implement those solutions designed to optimize each of the 4P of marketing mix: product (quality), price, distribution (placement) and promotion. The communication program has an essential role, because the company presents through it its ...

  12. Propagating Uncertainty in Solar Panel Performance for Life Cycle Modeling in Early Stage Design

    OpenAIRE

    Honda, Tomonori; Chen, Heidi Qianyi; Chan, Kennis Y.; Yang, Maria

    2011-01-01

    One of the challenges in accurately applying metrics for life cycle assessment lies in accounting for both irreducible and inherent uncertainties in how a design will perform under real world conditions. This paper presents a preliminary study that compares two strategies, one simulation-based and one set-based, for propagating uncertainty in a system. These strategies for uncertainty propagation are then aggregated. This work is conducted in the context of an amorphou...

  13. Stochastic Polynomial Dynamic Models of the Yeast Cell Cycle

    Science.gov (United States)

    Mitra, Indranil; Dimitrova, Elena; Jarrah, Abdul S.

    2010-03-01

    In the last decade a new holistic approach for tackling biological problems, systems biology, which takes into account the study of the interactions between the components of a biological system to predict function and behavior has emerged. The reverse-engineering of biochemical networks from experimental data have increasingly become important in systems biology. Based on Boolean networks, we propose a time-discrete stochastic framework for the reverse engineering of the yeast cell cycle regulatory network from experimental data. With a suitable choice of state set, we have used powerful tools from computational algebra, that underlie the reverse-engineering algorithm, avoiding costly enumeration strategies. Stochasticity is introduced by choosing at each update step a random coordinate function for each variable, chosen from a probability space of update functions. The algorithm is based on a combinatorial structure known as the Gr"obner fans of a polynomial ideal which identifies the underlying network structure and dynamics. The model depicts a correct dynamics of the yeast cell cycle network and reproduces the time sequence of expression patterns along the biological cell cycle. Our findings indicate that the methodolgy has high chance of success when applied to large and complex systems to determine the dynamical properties of corresponding networks.

  14. Complete and limited proteolysis in cell cycle progression.

    Science.gov (United States)

    Goulet, Brigitte; Nepveu, Alain

    2004-08-01

    An important mechanism of regulation that controls progression through the cell cycle involves the timely degradation of specific regulatory proteins. In parallel to the main degradative pathways, it appears that the function of certain proteins may also be modulated by a process called limited proteolysis. We have recently shown that the CDP/Cux transcription factor is proteolytically processed at the G(1)/S transition by the cathepsin L protease. Two aspects of these findings are discussed in the context of the cell cycle. Firstly, together with the cohesin subunit Scc1 and the HCF-1 factor, CDP/Cux represents a third example whereby the process of "limited proteolysis" plays a role in the control of cell cycle progression. Secondly, our findings provides compelling evidence that the cathepsin L protease, which was believed to be obligatorily targeted through the endoplasmic reticulum to the lysosomes or the extra-cellular milieu, could also be present in the nucleus and modulate the function of transcription factors. PMID:15254406

  15. FAT10, a gene up-regulated in various cancers, is cell-cycle regulated

    OpenAIRE

    Zhang Dongwei; Lim Chuan-Bian; Lee Caroline GL

    2006-01-01

    Abstract Background FAT10 is a member of the ubiquitin-like-modifier family of proteins. Over-expression of the FAT10 gene was observed in the tumors of several epithelial cancers. High FAT10 expression was found to lead to increased chromosome instability via the reduction in the kinetochore localization of MAD2 during the prometaphase stage of the cell-cycle. FAT10 expression was also previously reported to be regulated by cytokines and p53. Results Here, we report that FAT10 expression is ...

  16. Exosomes Secreted by Toxoplasma gondii-Infected L6 Cells: Their Effects on Host Cell Proliferation and Cell Cycle Changes

    Science.gov (United States)

    Kim, Min Jae; Jung, Bong-Kwang; Cho, Jaeeun; Song, Hyemi; Pyo, Kyung-Ho; Lee, Ji Min; Kim, Min-Kyung; Chai, Jong-Yil

    2016-01-01

    Toxoplasma gondii infection induces alteration of the host cell cycle and cell proliferation. These changes are not only seen in directly invaded host cells but also in neighboring cells. We tried to identify whether this alteration can be mediated by exosomes secreted by T. gondii-infected host cells. L6 cells, a rat myoblast cell line, and RH strain of T. gondii were selected for this study. L6 cells were infected with or without T. gondii to isolate exosomes. The cellular growth patterns were identified by cell counting with trypan blue under confocal microscopy, and cell cycle changes were investigated by flow cytometry. L6 cells infected with T. gondii showed decreased proliferation compared to uninfected L6 cells and revealed a tendency to stay at S or G2/M cell phase. The treatment of exosomes isolated from T. gondii-infected cells showed attenuation of cell proliferation and slight enhancement of S phase in L6 cells. The cell cycle alteration was not as obvious as reduction of the cell proliferation by the exosome treatment. These changes were transient and disappeared at 48 hr after the exosome treatment. Microarray analysis and web-based tools indicated that various exosomal miRNAs were crucial for the regulation of target genes related to cell proliferation. Collectively, our study demonstrated that the exosomes originating from T. gondii could change the host cell proliferation and alter the host cell cycle. PMID:27180572

  17. Mast cells dysregulate apoptotic and cell cycle genes in mucosal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Davis Paul

    2006-12-01

    Full Text Available Abstract Background Mucosal squamous cell carcinoma of the head and neck is a disease of high mortality and morbidity. Interactions between the squamous cell carcinoma and the host's local immunity, and how the latter contributes to the biological behavior of the tumor are unclear. In vivo studies have demonstrated sequential mast cell infiltration and degranulation during squamous cell carcinogenesis. The degree of mast cell activation correlates closely with distinct phases of hyperkeratosis, dysplasia, carcinoma in-situ and invasive carcinoma. However, the role of mast cells in carcinogenesis is unclear. Aim This study explores the effects of mast cells on the proliferation and gene expression profile of mucosal squamous cell carcinoma using human mast cell line (HMC-1 and human glossal squamous cell carcinoma cell line (SCC25. Methods HMC-1 and SCC25 were co-cultured in a two-compartment chamber, separated by a polycarbonate membrane. HMC-1 was stimulated to degranulate with calcium ionophore A23187. The experiments were done in quadruplicate. Negative controls were established where SCC25 were cultured alone without HMC-1. At 12, 24, 48 and 72 hours, proliferation and viability of SCC25 were assessed with MTT colorimetric assay. cDNA microarray was employed to study differential gene expression between co-cultured and control SCC25. Results HMC-1/SCC25 co-culture resulted in suppression of growth rate for SCC-25 (34% compared with 110% for the control by 72 hours, p Conclusion We show that mast cells have a direct inhibitory effect on the proliferation of mucosal squamous cell carcinoma in vitro by dysregulating key genes in apoptosis and cell cycle control.

  18. Population structure and maturity stages of Fritillaria borealis (Appendicularia, Tunicata): seasonal cycle in Ushuaia Bay (Beagle Channel)

    OpenAIRE

    María Laura Presta; Mónica Susana Hoffmeyer; Fabiana Lia Capitanio

    2015-01-01

    AbstractFritillaria borealis is a cosmopolitan species, very frequent in sub-antarctic and antarctic waters. The objective of this paper was to analyze its size structure and maturity stages at two sites in Ushuaia Bay: a coastal site exposed to anthropogenic pressure (E1) and a reference site (E2) located in the external zone of the bay. Zooplankton was collected during the 2012 seasonal cycle. The sampling method involved the use of a 67 µm-mesh net. Appendicularians were classified in four...

  19. SHP1-mediated cell cycle redistribution inhibits radiosensitivity of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Radioresistance is the common cause for radiotherapy failure in non-small cell lung cancer (NSCLC), and the degree of radiosensitivity of tumor cells is different during different cell cycle phases. The objective of the present study was to investigate the effects of cell cycle redistribution in the establishment of radioresistance in NSCLC, as well as the signaling pathway of SH2 containing Tyrosine Phosphatase (SHP1). A NSCLC subtype cell line, radioresistant A549 (A549S1), was induced by high-dose hypofractionated ionizing radiations. Radiosensitivity-related parameters, cell cycle distribution and expression of cell cycle-related proteins and SHP1 were investigated. siRNA was designed to down-regulate SHP1expression. Compared with native A549 cells, the proportion of cells in the S phase was increased, and cells in the G0/G1 phase were consequently decreased, however, the proportion of cells in the G2/M phase did not change in A549S1 cells. Moreover, the expression of SHP1, CDK4 and CylinD1 were significantly increased, while p16 was significantly down-regulated in A549S1 cells compared with native A549 cells. Furthermore, inhibition of SHP1 by siRNA increased the radiosensitivity of A549S1 cells, induced a G0/G1 phase arrest, down-regulated CDK4 and CylinD1expressions, and up-regulated p16 expression. SHP1 decreases the radiosensitivity of NSCLC cells through affecting cell cycle distribution. This finding could unravel the molecular mechanism involved in NSCLC radioresistance

  20. A genetic interaction map of cell cycle regulators.

    Science.gov (United States)

    Billmann, Maximilian; Horn, Thomas; Fischer, Bernd; Sandmann, Thomas; Huber, Wolfgang; Boutros, Michael

    2016-04-15

    Cell-based RNA interference (RNAi) is a powerful approach to screen for modulators of many cellular processes. However, resulting candidate gene lists from cell-based assays comprise diverse effectors, both direct and indirect, and further dissecting their functions can be challenging. Here we screened a genome-wide RNAi library for modulators of mitosis and cytokinesis inDrosophilaS2 cells. The screen identified many previously known genes as well as modulators that have previously not been connected to cell cycle control. We then characterized ∼300 candidate modifiers further by genetic interaction analysis using double RNAi and a multiparametric, imaging-based assay. We found that analyzing cell cycle-relevant phenotypes increased the sensitivity for associating novel gene function. Genetic interaction maps based on mitotic index and nuclear size grouped candidates into known regulatory complexes of mitosis or cytokinesis, respectively, and predicted previously uncharacterized components of known processes. For example, we confirmed a role for theDrosophilaCCR4 mRNA processing complex componentl(2)NC136during the mitotic exit. Our results show that the combination of genome-scale RNAi screening and genetic interaction analysis using process-directed phenotypes provides a powerful two-step approach to assigning components to specific pathways and complexes. PMID:26912791

  1. CDK inhibitors, p21{sup Cip1} and p27{sup Kip1}, participate in cell cycle exit of mammalian cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Tane, Shoji; Ikenishi, Aiko; Okayama, Hitomi; Iwamoto, Noriko [School of Life Sciences, Faculty of Medicine, Tottori University, Yonago 683-8503 (Japan); Nakayama, Keiichi I. [Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582 (Japan); Takeuchi, Takashi, E-mail: takeuchi@med.tottori-u.ac.jp [School of Life Sciences, Faculty of Medicine, Tottori University, Yonago 683-8503 (Japan)

    2014-01-17

    Highlights: •Expression of p21 and p27 in the hearts showed a peak during postnatal stages. •p21 and p27 bound to cyclin E, cyclin A and CDK2 in the hearts at postnatal stages. •Cardiomyocytes in both KO mice showed failure in the cell cycle exit at G1-phase. •These data show the first apparent phenotypes in the hearts of Cip/Kip KO mice. -- Abstract: Mammalian cardiomyocytes actively proliferate during embryonic stages, following which cardiomyocytes exit their cell cycle after birth. The irreversible cell cycle exit inhibits cardiac regeneration by the proliferation of pre-existing cardiomyocytes. Exactly how the cell cycle exit occurs remains largely unknown. Previously, we showed that cyclin E- and cyclin A-CDK activities are inhibited before the CDKs levels decrease in postnatal stages. This result suggests that factors such as CDK inhibitors (CKIs) inhibit CDK activities, and contribute to the cell cycle exit. In the present study, we focused on a Cip/Kip family, which can inhibit cyclin E- and cyclin A-CDK activities. Expression of p21{sup Cip1} and p27{sup Kip1} but not p57{sup Kip2} showed a peak around postnatal day 5, when cyclin E- and cyclin A-CDK activities start to decrease. p21{sup Cip1} and p27{sup Kip1} bound to cyclin E, cyclin A and CDK2 at postnatal stages. Cell cycle distribution patterns of postnatal cardiomyocytes in p21{sup Cip1} and p27{sup Kip1} knockout mice showed failure in the cell cycle exit at G1-phase, and endoreplication. These results indicate that p21{sup Cip1} and p27{sup Kip} play important roles in the cell cycle exit of postnatal cardiomyocytes.

  2. Characterization and Evolution of the Cell Cycle-Associated Mob Domain-Containing Proteins in Eukaryotes

    Directory of Open Access Journals (Sweden)

    Nicola Vitulo

    2007-01-01

    Full Text Available The MOB family includes a group of cell cycle-associated proteins highly conserved throughout eukaryotes, whose founding members are implicated in mitotic exit and co-ordination of cell cycle progression with cell polarity and morphogenesis. Here we report the characterization and evolution of the MOB domain-containing proteins as inferred from the 43 eukaryotic genomes so far sequenced. We show that genes for Mob-like proteins are present in at least 41 of these genomes, confi rming the universal distribution of this protein family and suggesting its prominent biological function. The phylogenetic analysis reveals fi ve distinct MOB domain classes, showing a progressive expansion of this family from unicellular to multicellular organisms, reaching the highest number in mammals. Plant Mob genes appear to have evolved from a single ancestor, most likely after the loss of one or more genes during the early stage of Viridiplantae evolutionary history. Three of the Mob classes are widespread among most of the analyzed organisms. The possible biological and molecular function of Mob proteins and their role in conserved signaling pathways related to cell proliferation, cell death and cell polarity are also presented and critically discussed.

  3. Sm14 gene expression in different stages of the Schistosoma mansoni life cycle and immunolocalization of the Sm14 protein within the adult worm

    Directory of Open Access Journals (Sweden)

    C.F.A. Brito

    2002-03-01

    Full Text Available Sm14 is a 14-kDa vaccine candidate antigen from Schistosoma mansoni that seems to be involved in cytoplasmic trafficking of fatty acids. Although schistosomes have a high requirement for lipids, they are not able to synthesize fatty acids and sterols de novo. Thus, they must acquire host lipids. In order to determine whether Sm14 is present in different stages of the life cycle of the parasite, we performed RT-PCR. Sm14 mRNA was identified in all stages of the life cycle studied, mainly schistosomulum, adult worm and egg. Additionally, we used a rabbit anti-Sm14 polyclonal antibody in an indirect immunofluorescence assay to localize Sm14 in adult worm sections. The basal lamella of the tegument and the gut epithelium were strongly labeled. These tissues have a high flow of and demand for lipids, a finding that supports the putative role of Sm14 as an intracellular transporter of fatty acids from host cells.

  4. Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence

    OpenAIRE

    San-Yuan Chen; Geng-Hung Liu; Wen-Ying Chao; Chung-Sheng Shi; Ching-Yen Lin; Yun-Ping Lim; Chieh-Hsiang Lu; Peng-Yeh Lai; Hau-Ren Chen; Ying-Ray Lee

    2016-01-01

    Oral squamous cell carcinoma (OSCC), an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL), a natural compound isolated from Piper longum L., in human OSCC cells. The effects of PL on cell proliferation, the cell cycle, apoptosis, senescence and reactive oxygen species (ROS) levels in human OSCC cells were investigated. PL effectively inhibited ...

  5. Silicon Phthalocyanine 4 and Photodynamic Therapy in Stage IA-IIA Cutaneous T-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2015-12-03

    Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome

  6. Expression and clinical role of NF45 as a novel cell cycle protein in esophageal squamous cell carcinoma (ESCC).

    Science.gov (United States)

    Ni, Sujie; Zhu, Junya; Zhang, Jianguo; Zhang, Shu; Li, Mei; Ni, Runzhou; Liu, Jinxia; Qiu, Huiyuan; Chen, Wenjuan; Wang, Huijie; Guo, Weijian

    2015-02-01

    NF45 (also known as ILF2), as one subunit of NF-AT (nuclear factor of activated T cells), repairs DNA breaks, inhibits viral replication, and also functions as a negative regulator in the microRNA processing pathway in combination with NF90. Recently, it was found that implicated in the mitotic control of HeLa cells and deletion of endogenous NF45 decreases growth of HeLa cells. While the role of NF45 in cancer biology remains under debate. In this study, we analyzed the expression and clinical significance of NF45 in esophageal squamous cell carcinoma ESCC. The expression of NF45 was evaluated by Western blot in 8 paired fresh ESCC tissues and immunohistochemistry on 105 paraffin-embedded slices. NF45 was highly expressed in ESCC and significantly associated with ESCC cells tumor stage and Ki-67. Besides, high NF45 expression was an independent prognostic factor for ESCC patients' poor survival. To determine whether NF45 could regulate the proliferation of ESCC cells, we increased endogenous NF45 and analyzed the proliferation of TE1 ESCC cells using Western blot, CCK8, flow cytometry assays and colony formation analyses, which together indicated that overexpression of NF45 favors cell cycle progress of TE1 ESCC cells. While knockdown of NF45 resulted in cell cycle arrest at G0/G1-phase and thus abolished the cell growth. These findings suggested that NF45 might play an important role in promoting the tumorigenesis of ESCC, and thus be a promising therapeutic target to prevent ESCC progression. PMID:25286760

  7. FoxM1, a forkhead transcription factor is a master cell cycle regulator for mouse mature T cells but not double positive thymocytes.

    Directory of Open Access Journals (Sweden)

    Ling Xue

    Full Text Available FoxM1 is a forkhead box transcription factor and a known master regulator required for different phases of the cell cycle. In cell lines, FoxM1 deficient cells exhibit delayed S phase entry, aneuploidy, polyploidy and can't complete mitosis. In vivo, FoxM1 is expressed mostly in proliferating cells but is surprisingly also found in non-proliferating CD4(+CD8(+ double positive thymocytes. Here, we addressed the role of FoxM1 in T cell development by generating and analyzing two different lines of T-cell specific FoxM1 deficient mice. As expected, FoxM1 is required for proliferation of early thymocytes and activated mature T cells. Defective expression of many cell cycle proteins was detected, including cyclin A, cyclin B1, cdc2, cdk2, p27 and the Rb family members p107 and p130 but surprisingly not survivin. Unexpectedly, loss of FoxM1 only affects a few cell cycle proteins in CD4(+CD8(+ thymocytes and has little effect on their sensitivity to apoptosis and the subsequent steps of T cell differentiation. Thus, regulation of cell cycle genes by FoxM1 is stage- and context-dependent.

  8. Endothelial adhesion of synchronized gastric tumor cells changes during cell cycle transit and correlates with the expression level of CD44 splice variants

    Institute of Scientific and Technical Information of China (English)

    Anton Oertl; Jens Castein; Tobias Engl; Wolf-Dietrich Beecken; Dietger Jonas; Richard Melamed; Roman A. Blaheta

    2005-01-01

    AIM: To study adhesion capacity and CD44 expression of human gastric adenocarcinoma MKN45 cells at different stages of a first cell cycle.METHODS: MKN45 cells were synchronized by aphidicolin and assayed for adhesion to an endothelial cell (HUVEC)monolayer. Surface expression of CD44 and CD44 splice variants on MKN45 cells was evaluated by flow cytometry.Functional relevance of CD44 adhesion receptors was investigated by blocking studies using anti CD44 monoclonal antibodies or by hyaluronan digestion.RESULTS: Adhesion of MKN45 to HUVEC was increased during G2/M transit, after which adhesion returned to baseline levels with cell cycle completion. In parallel, CD44splice variants CD44v4, CD44v5, and CD44v7 were all upregulated on MKN45 during cell cycle progression with a maximum effect in G2/M. The function of CD44 surface receptors was assessed with specific receptor blocking monodonal antibodies or removal of hyaluronan by digestion with hyaluronidase. Both strategies inhibited tumor cell adhesion to HUVEC by nearly 50%, which indicates that MKN45-HUVEC-interaction is CD44 dependent.CONCLUSION: CD44 expression level is linked to the cell cycle in gastrointestinal tumor cells, which in turn leads to cell cyde dependent alterations of their adhesion behaviour to endothelium.

  9. Reliability of transcriptional cycles and the yeast cell-cycle oscillator.

    Directory of Open Access Journals (Sweden)

    Volkan Sevim

    Full Text Available A recently published transcriptional oscillator associated with the yeast cell cycle provides clues and raises questions about the mechanisms underlying autonomous cyclic processes in cells. Unlike other biological and synthetic oscillatory networks in the literature, this one does not seem to rely on a constitutive signal or positive auto-regulation, but rather to operate through stable transmission of a pulse on a slow positive feedback loop that determines its period. We construct a continuous-time Boolean model of this network, which permits the modeling of noise through small fluctuations in the timing of events, and show that it can sustain stable oscillations. Analysis of simpler network models shows how a few building blocks can be arranged to provide stability against fluctuations. Our findings suggest that the transcriptional oscillator in yeast belongs to a new class of biological oscillators.

  10. Reliability of transcriptional cycles and the yeast cell-cycle oscillator.

    Science.gov (United States)

    Sevim, Volkan; Gong, Xinwei; Socolar, Joshua E S

    2010-01-01

    A recently published transcriptional oscillator associated with the yeast cell cycle provides clues and raises questions about the mechanisms underlying autonomous cyclic processes in cells. Unlike other biological and synthetic oscillatory networks in the literature, this one does not seem to rely on a constitutive signal or positive auto-regulation, but rather to operate through stable transmission of a pulse on a slow positive feedback loop that determines its period. We construct a continuous-time Boolean model of this network, which permits the modeling of noise through small fluctuations in the timing of events, and show that it can sustain stable oscillations. Analysis of simpler network models shows how a few building blocks can be arranged to provide stability against fluctuations. Our findings suggest that the transcriptional oscillator in yeast belongs to a new class of biological oscillators. PMID:20628620

  11. Low cycle fatigue analysis of a last stage steam turbine blade

    Directory of Open Access Journals (Sweden)

    Měšťánek P.

    2008-11-01

    Full Text Available The present paper deals with the low cycle fatigue analysis of the low pressure (LP steam turbine blade. The blade is cyclically loaded by the centrifugal force because of the repeated startups of the turbine. The goal of the research is to develop a technique to assess fatigue life of the blade and to determine the number of startups to the crack initiation. Two approaches were employed. First approach is based on the elastic finite element analysis. Fictive 'elastic' results are recalculated using Neuber's rule and the equivalent energy method. Triaxial state of stress is reduced using von Mises theory. Strain amplitude is calculated employing the cyclic deformation curve. Second approach is based on elastic-plastic FE analysis. Strain amplitude is determined directly from the FE analysis by reducing the triaxial state of strain. Fatigue life was assessed using uniaxial damage parameters. Both approaches are compared and their applicability is discussed. Factors that can influence the fatigue life are introduced. Experimental low cycle fatigue testing is shortly described.

  12. Modeling cell-cycle synchronization during embryogenesis in Xenopus laevis

    Science.gov (United States)

    McIsaac, R. Scott; Huang, K. C.; Sengupta, Anirvan; Wingreen, Ned

    2010-03-01

    A widely conserved aspect of embryogenesis is the ability to synchronize nuclear divisions post-fertilization. How is synchronization achieved? Given a typical protein diffusion constant of 10 μm^2sec, and an embryo length of 1mm, it would take diffusion many hours to propagate a signal across the embryo. Therefore, synchrony cannot be attained by diffusion alone. We hypothesize that known autocatalytic reactions of cell-cycle components make the embryo an ``active medium'' in which waves propagate much faster than diffusion, enforcing synchrony. We report on robust spatial synchronization of components of the core cell cycle circuit based on a mathematical model previously determined by in vitro experiments. In vivo, synchronized divisions are preceded by a rapid calcium wave that sweeps across the embryo. Experimental evidence supports the hypothesis that increases in transient calcium levels lead to derepression of a negative feedback loop, allowing cell divisions to start. Preliminary results indicate a novel relationship between the speed of the initial calcium wave and the ability to achieve synchronous cell divisions.

  13. (p)ppGpp and the bacterial cell cycle

    Indian Academy of Sciences (India)

    Aanisa Nazir; Rajendran Harinarayanan

    2016-06-01

    Genes of the Rel/Spo homolog (RSH) superfamily synthesize and/or hydrolyse the modified nucleotides pppGpp/ppGpp (collectively referred to as (p)ppGpp) and are prevalent across diverse bacteria and in plant chloroplasts. Bacteria accumulate (p)ppGpp in response to nutrient deprivation (generically called the stringent response) and elicit appropriate adaptive responses mainly through the regulation of transcription. Although at different concentrations (p)ppGpp affect the expression of distinct set of genes, the two well-characterized responses are reduction in expression of the protein synthesis machinery and increase in the expression of genes coding for amino acid biosynthesis. In Escherichia coli, the cellular (p)ppGpp level inversely correlates with the growth rate and increasing its concentration decreases the steady state growth rate in a defined growth medium. Since change in growth rate must be accompanied by changes in cell cycle parameters set through the activities of the DNA replication and cell division apparatus, (p)ppGpp could coordinate protein synthesis (cell mass increase) with these processes. Here we review the role of (p)ppGpp in bacterial cell cycle regulation.

  14. Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage III Ovarian Cancer

    Science.gov (United States)

    2016-03-17

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  15. Life-cycle stages of a Posthodiplostomum species (Digenea: Diplostomidae) from Patagonia, Argentina.

    Science.gov (United States)

    Ritossa, Luciano; Flores, Verónica; Viozzi, Gustavo

    2013-10-01

    In Patagonia, populations of the galaxiid fish Galaxias maculatus are parasitized by metacercariae of a species of Posthodiplostomum (Digenea: Diplostomidae). The aim of this work was to describe larval and adult stages of this species in experimental and natural hosts from an Andean Patagonian lake. Specimens of G. maculatus and the pulmonate snail, Anisancylus obliquus, were collected in Patagua Lake. The snails were isolated in individual containers to observe emergence of cercariae, dissected, and examined under a stereoscopic microscope to record sporocysts and cercariae. Fish were examined to obtain metacercariae, and uninfected fish from Gutiérrez Lake were exposed to cercariae from A. obliquus to obtain experimental metacercariae. Chicks and mice were infected with metacercariae from naturally infected G. maculatus to obtain experimental adults. Specimens recovered belong to Posthodiplostomum sp. on the basis of morphological features. This is the first description of sporocysts, cercariae, metacercariae, and adults stages of a Posthodiplostomum species in Patagonia, including data about its natural intermediate hosts. PMID:23628085

  16. Coupling between the Circadian Clock and Cell Cycle Oscillators: Implication for Healthy Cells and Malignant Growth

    Science.gov (United States)

    Feillet, Celine; van der Horst, Gijsbertus T. J.; Levi, Francis; Rand, David A.; Delaunay, Franck

    2015-01-01

    Uncontrolled cell proliferation is one of the key features leading to cancer. Seminal works in chronobiology have revealed that disruption of the circadian timing system in mice, either by surgical, genetic, or environmental manipulation, increased tumor development. In humans, shift work is a risk factor for cancer. Based on these observations, the link between the circadian clock and cell cycle has become intuitive. But despite identification of molecular connections between the two processes, the influence of the clock on the dynamics of the cell cycle has never been formally observed. Recently, two studies combining single live cell imaging with computational methods have shed light on robust coupling between clock and cell cycle oscillators. We recapitulate here these novel findings and integrate them with earlier results in both healthy and cancerous cells. Moreover, we propose that the cell cycle may be synchronized or slowed down through coupling with the circadian clock, which results in reduced tumor growth. More than ever, systems biology has become instrumental to understand the dynamic interaction between the circadian clock and cell cycle, which is critical in cellular coordination and for diseases such as cancer. PMID:26029155

  17. Coupling between the circadian clock and cell cycle oscillators: implication for healthy cells and malignant growth

    Directory of Open Access Journals (Sweden)

    Celine eFeillet

    2015-05-01

    Full Text Available Uncontrolled cell proliferation is one of the key features leading to cancer. Seminal works in chronobiology have revealed that disruption of the circadian timing system in mice, either by surgical, genetic or environmental manipulation, increased tumor development. In humans, shift work is a risk factor for cancer. Based on these observations, the link between the circadian clock and cell cycle has become intuitive. But despite identification of molecular connections between the two processes, the influence of the clock on the dynamics of the cell cycle has never been formally observed. Recently, two studies combining single live cell imaging with computational methods have shed light on robust coupling between clock and cell cycle oscillators. We recapitulate here these novel findings and integrate them with earlier results in both healthy and cancerous cells. Moreover, we propose that the cell cycle may be synchronized or slowed down through coupling with the circadian clock, which results in reduced tumour growth. More than ever, systems biology has become instrumental to understand the dynamic interaction between the circadian clock and cell cycle, which is critical in cellular coordination and for diseases such as cancer.

  18. Morphometry and morphology of nucleus of the Sertoli and interstitial cells of the tambaqui Colossoma macropomum (Cuvier, 1881) (Pisces: Characidae) during the reproductive cycle.

    Science.gov (United States)

    Nakaghi, L S O; Mitsuiki, D; Santos, H S L; Pacheco, M R; Ganeco, L N

    2003-02-01

    This study allowed the characterization of the tambaqui Colossoma macropomum testes structural organization, emphasizing Sertoli and interstitial cells and analyzing morphometrically the Sertoli cell nucleus diameter and the interstitial tissue area during the reproductive cycle. Fragments of tambaqui testes were collected in the following reproductive cycle stages: immature, resting, maturation I and II, mature, and regression, and were histologically processed. The Sertoli cells were found at the periphery of the cysts of germinative lineage cells and the nuclei were shown to be smaller as these cells developed. The interstitial cells were better observed between the seminiferous lobules next to vessels in the interstitial tissue of maturing testes. PMID:12914420

  19. BRCA1 May Modulate Neuronal Cell Cycle Re-Entry in Alzheimer Disease

    OpenAIRE

    Evans, Teresa A.; Raina, Arun K; Delacourte, André; Aprelikova, Olga; Lee, Hyoung-gon; Zhu, Xiongwei; Perry, George; Smith, Mark A.

    2007-01-01

    In Alzheimer disease, neuronal degeneration and the presence of neurofibrillary tangles correlate with the severity of cognitive decline. Neurofibrillary tangles contain the antigenic profile of many cell cycle markers, reflecting a re-entry into the cell cycle by affected neurons. However, while such a cell cycle re-entry phenotype is an early and consistent feature of Alzheimer disease, the mechanisms responsible for neuronal cell cycle are unclear. In this regard, given that a dysregulated...

  20. Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Xiaolan, E-mail: huxiaolan1998@yahoo.com.cn [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou (China); Zhang, Xianqi [The 2nd Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou (China); Qiu, Shuifeng [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou (China); Yu, Daihua; Lin, Shuxin [Fourth Military Medical University, Xi' an (China)

    2010-07-16

    Research highlights: {yields} Salidroside inhibits the growth of human breast cancer cells. {yields} Salidroside induces cell-cycle arrest of human breast cancer cells. {yields} Salidroside induces apoptosis of human breast cancer cell lines. -- Abstract: Recently, salidroside (p-hydroxyphenethyl-{beta}-D-glucoside) has been identified as one of the most potent compounds isolated from plants of the Rhodiola genus used widely in traditional Chinese medicine, but pharmacokinetic data on the compound are unavailable. We were the first to report the cytotoxic effects of salidroside on cancer cell lines derived from different tissues, and we found that human breast cancer MDA-MB-231 cells (estrogen receptor negative) were sensitive to the inhibitory action of low-concentration salidroside. To further investigate the cytotoxic effects of salidroside on breast cancer cells and reveal possible ER-related differences in response to salidroside, we used MDA-MB-231 cells and MCF-7 cells (estrogen receptor-positive) as models to study possible molecular mechanisms; we evaluated the effects of salidroside on cell growth characteristics, such as proliferation, cell cycle duration, and apoptosis, and on the expression of apoptosis-related molecules. Our results demonstrated for the first time that salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells and may be a promising candidate for breast cancer treatment.

  1. Berberine induces cell cycle arrest and apoptosis in human gastric carcinoma SNU-5 cell line

    Institute of Scientific and Technical Information of China (English)

    Jing-Pin Lin; Jai-Sing Yang; Jau-Hong Lee; Wen-Tsong Hsieh; Jing-Gung Chung

    2006-01-01

    AIM: To investigate the relationship between the inhibited growth (cytotoxic activity) of berberine and apoptotic pathway with its molecular mechanism of action.METHODS: The in vitro cytotoxic techniques were complemented by cell cycle analysis and determination of sub-G1 for apoptosis in human gastric carcinoma SNU-5 cells. Percentage of viable cells, cell cycle, and sub-G1 group (apoptosis) were examined and determined by the flow cytometric methods. The associated proteins for cell cycle arrest and apoptosis were examined by Western blotting.RESULTS: For SNU-5 cell line, the IC (50) was found to be 48 μmol/L of berberine. In SNU-5 cells treated with 25-200 μmol/L berberine, G2/M cell cycle arrest was observed which was associated with a marked increment of the expression of p53, Wee1 and CDk1 proteins and decreased cyclin B. A concentration-dependent decrease of cells in G0/G1 phase and an increase in G2/M phase were detected. In addition, apoptosis detected as sub-G0 cell population in cell cycle measurement was proved in 25-200 μmol/L berberine-treated cells by monitoring the apoptotic pathway. Apoptosis was identified by sub-G0 cell population, and upregulation of Bax, downregulation of Bcl-2, release of Ca2+, decreased the mitochondrial membrane potential and then led to the release of mitochondrial cytochrome C into the cytoplasm and caused the activation of caspase-3, and finally led to the occurrence of apoptosis.CONCLUSION: Berberine induces p53 expression and leads to the decrease of the mitochondrial membrane potential, Cytochrome C release and activation of caspase-3 for the induction of apoptosis.

  2. Structural and genomic properties of the hyperthermophilic archaeal virus ATV with an extracellular stage of the reproductive cycle

    DEFF Research Database (Denmark)

    Prangishvili, David; Vestergaard, Gisle Alberg; Häring, Monika;

    2006-01-01

    a crenarchaeal virus, infection with ATV results either in viral replication and subsequent cell lysis or in conversion of the infected cell to a lysogen. The lysogenic cycle involves integration of the viral genome into the host chromosome, probably facilitated by the virus-encoded integrase and......A novel virus, ATV, of the hyperthermophilic archaeal genus Acidianus has the unique property of undergoing a major morphological development outside of, and independently of, the host cell. Virions are extruded from host cells as lemon-shaped tail-less particles, after which they develop long...... periodic structure. Tail development produces a one half reduction in the volume of the virion, concurrent with a slight expansion of the virion surface. The circular, double-stranded DNA genome contains 62,730 bp and is exceptional for a crenarchaeal virus in that it carries four putative transposable...

  3. Outcomes of patients with unresected stage III and stage IV non-small cell lung cancer: A single institution experience

    Directory of Open Access Journals (Sweden)

    Manpreet Singh Tiwana

    2013-01-01

    Full Text Available Introduction: To report on the demographic profile and survival outcomes of North Indian population affected with stage III and stage IV non-small cell lung cancer (NSCLC. Materials and Methods: From November 2008 to January 2012, 138 consecutively diagnosed NSCLC patients were included in this study. The patient, tumor and treatment related factors were analyzed. Median overall survival (OS, Kaplan-Meier survival plots, t-test, Cox proportional hazards models were generated by multivariate analysis [MVA] and analyzed on SPSS software (version 19.0; SPSS, Inc., Chicago, IL. Results: Median OS of stage III patients was 9.26 ± 1.85 months and 2-year survival rate of 13% while stage IV patients had median OS of 5 ± 1.5 months with a 2-year survival rate of 8%. Cox regression modeling for MVA demonstrated higher biologically equivalent dose (BED ( P = 0.01 in stage III while in stage IV non-squamous histology ( P = 0.01, administration of chemotherapy ( P = 0.02, partial responders to chemotherapy ( P = 0.001, higher BED ( P = 0.02, and those with skeletal metastasis alone ( P = 0.17 showed a better OS. Conclusion: Our data showed that a higher BED is associated with favorable outcomes, indicating a role of dose escalated radiation therapy to the primary lesion in both stage III and essentially in stage IV NSCLC. Additionally, optimal use of chemotherapy relates to better survival. The developing, resource restrained nations need to follow an economically feasible multimodality approach.

  4. PET/CT for staging and monitoring non small cell lung cancer

    OpenAIRE

    Rankin, Sheila

    2008-01-01

    Abstract Correct staging of non small cell lung cancer (NSCLC) is vital for appropriate management. Initial staging is usually performed with computerised tomography (CT), but increasingly functional imaging using integrated positron emission tomography and CT (PET/CT) is being used to provide more accurate staging, guide biopsies, assess response to therapy and identify recurrent disease.

  5. Integrative analysis of cell cycle control in budding yeast.

    Science.gov (United States)

    Chen, Katherine C; Calzone, Laurence; Csikasz-Nagy, Attila; Cross, Frederick R; Novak, Bela; Tyson, John J

    2004-08-01

    The adaptive responses of a living cell to internal and external signals are controlled by networks of proteins whose interactions are so complex that the functional integration of the network cannot be comprehended by intuitive reasoning alone. Mathematical modeling, based on biochemical rate equations, provides a rigorous and reliable tool for unraveling the complexities of molecular regulatory networks. The budding yeast cell cycle is a challenging test case for this approach, because the control system is known in exquisite detail and its function is constrained by the phenotypic properties of >100 genetically engineered strains. We show that a mathematical model built on a consensus picture of this control system is largely successful in explaining the phenotypes of mutants described so far. A few inconsistencies between the model and experiments indicate aspects of the mechanism that require revision. In addition, the model allows one to frame and critique hypotheses about how the division cycle is regulated in wild-type and mutant cells, to predict the phenotypes of new mutant combinations, and to estimate the effective values of biochemical rate constants that are difficult to measure directly in vivo. PMID:15169868

  6. Stages of Plasma Cell Neoplasms (Including Multiple Myeloma)

    Science.gov (United States)

    ... Treatment Health Professional Plasma Cell Neoplasms Treatment Research Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Patient Version General Information About Plasma Cell Neoplasms Go to Health Professional Version Key ...

  7. Coupling of the cell cycle and apoptotic machineries in developing T cells.

    Science.gov (United States)

    Xue, Ling; Sun, Yuefang; Chiang, Leslie; He, Bo; Kang, Chulho; Nolla, Hector; Winoto, Astar

    2010-03-01

    Proliferation and apoptosis are diametrically opposite processes. Expression of certain genes like c-Myc, however, can induce both, pointing to a possible linkage between them. Developing CD4(+)CD8(+) thymocytes are intrinsically sensitive to apoptosis, but the molecular basis is not known. We have found that these noncycling cells surprisingly express many cell cycle proteins. We generated transgenic mice expressing a CDK2 kinase-dead (CDK2-DN) protein in the T cell compartment. Analysis of these mice showed that the CDK2-DN protein acts as a dominant negative mutant in mature T cells as expected, but surprisingly, it acts as a dominant active protein in CD4(+)CD8(+) thymocytes. The levels of CDK2 kinase activity, cyclin E, cyclin A, and other cell cycle proteins in transgenic CD4(+)CD8(+) thymocytes are increased. Concurrently, caspase levels are elevated, and apoptosis is significantly enhanced in vitro and in vivo. E2F-1, the unique E2F member capable of inducing apoptosis when overexpressed, is specifically up-regulated in transgenic CD4(+)CD8(+) thymocytes but not in other T cell populations. These results demonstrate that the cell cycle and apoptotic machineries are normally linked, and expression of cell cycle proteins in developing T cells contributes to their inherent 1sensitivity to apoptosis. PMID:20068041

  8. Cell cycle arrest by a gradient of Dpp signaling during Drosophila eye development

    Directory of Open Access Journals (Sweden)

    Bhattacharya Abhishek

    2010-03-01

    Full Text Available Abstract Background The secreted morphogen Dpp plays important roles in spatial regulation of gene expression and cell cycle progression in the developing Drosophila eye. Dpp signaling is required for timely cell cycle arrest ahead of the morphogenetic furrow as a prelude to differentiation, and is also important for eye disc growth. The dpp gene is expressed at multiple locations in the eye imaginal disc, including the morphogenetic furrow that sweeps across the eye disc as differentiation initiates. Results Studies of Brinker and Dad expression, and of Mad phosphorylation, establish that there is a gradient of Dpp signaling in the eye imaginal disc anterior to the morphogenetic furrow, predominantly in the anterior-posterior axis, and also Dpp signaling at the margins of the disc epithelium and in the dorsal peripodial membrane. Almost all signaling activity seems to spread through the plane of the epithelia, although peripodial epithelium cells can also respond to underlying disc cells. There is a graded requirement for Dpp signaling components for G1 arrest in the eye disc, with more stringent requirements further anteriorly where signaling is lower. The signaling level defines the cell cycle response, because elevated signaling through expression of an activated Thickveins receptor molecule arrested cells at more anterior locations. Very anterior regions of the eye disc were not arrested in response to activated receptor, however, and evidence is presented that expression of the Homothorax protein may contribute to this protection. By contrast to activated Thickveins, ectopic expression of processed Dpp leads to very high levels of Mad phosphorylation which appear to have non-physiological consequences. Conclusions G1 arrest occurs at a threshold level of Dpp signaling within a morphogen gradient in the anterior eye. G1 arrest is specific for one competent domain in the eye disc, allowing Dpp signaling to promote growth at earlier

  9. Induction of cell-mediated immunity during early stages of infection with intracellular protozoa

    Directory of Open Access Journals (Sweden)

    Gazzinelli R.T.

    1998-01-01

    Full Text Available Toxoplasma gondii and Trypanosoma cruzi are intracellular parasites which, as part of their life cycle, induce a potent cell-mediated immunity (CMI maintained by Th1 lymphocytes and IFN-g. In both cases, induction of a strong CMI is thought to protect the host against rapid parasite multiplication and consequent pathology and lethality during the acute phase of infection. However, the parasitic infection is not eliminated by the immune system and the vertebrate host serves as a parasite reservoir. In contrast, Leishmania sp, which is a slow growing parasite, appears to evade induction of CMI during early stages of infection as a strategy for surviving in a hostile environment (i.e., inside the macrophages which are their obligatory niche in the vertebrate host. Recent reports show that the initiation of IL-12 synthesis by macrophages during these parasitic infections is a key event in regulating CMI and disease outcome. The studies reviewed here indicate that activation/inhibition of distinct signaling pathways and certain macrophage functions by intracellular protozoa are important events in inducing/modulating the immune response of their vertebrate hosts, allowing parasite and host survival and therefore maintaining parasite life cycles.

  10. Staging of non-small cell lung cancer (NSCLC)

    OpenAIRE

    Rankin, S. C.

    2006-01-01

    Staging of non-small lung cancer (NSCLC) uses the TNM classification and is undertaken to identify those patients who are surgical candidates, either initially or after chemo-radiotherapy, and to differentiate patients who will be treated radically from those requiring palliation and to plan radiotherapy fields. Computed tomography and magnetic resonance imaging (MRI) are used in staging and provide anatomical information but have well known limitations in differentiating reactive from malign...

  11. Sequential chemoradiotherapy for stage I/II nasal natural killer/T cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Young Joo [Ulsan University Hospital, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Ahn, Yong Chan; Kim, Won Seog; Ko, Young Hyeh [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2004-09-15

    Authors would report the results of sequential CHOP chemotherapy (cyclophosphamide, adriamycin, vincristine, and prednisone) and involved field radiotherapy (IFRT) for early stage nasal natural killer/T-cell lymphoma (NKTCL). Fourteen among 17 patients, who were registered at the Samsung Medical Center tumor registry with stage I and II nasal NKTCL from March 1995 to December 1999 received this treatment protocol. Three to four cycles of CHOP chemotherapy were given at 3 weeks' interval, which was followed by local IFRT including the known tumor extent and the adjacent draining lymphatics. Favorable responses after chemotherapy (before IFRT) were achievable only in seven patients (5 CR's + 2 PR's: 50%), while seven patients showed disease progression. There were six patients with local failures, two with distant relapses, and none with regional lymphatic failure. The actuarial overall survival and progression-free survival at 3 years were 50.0% and 42.9%. All the failures and deaths occurred within 13 months of the treatment start. The factors that correlated with the improved survival were the absence of 'B' symptoms, the favorable response to chemotherapy and overall treatment, and the low risk by international prognostic index on univariate analyses. Compared with the historic treatment results by IFRT either alone or followed by chemotherapy, the current trial failed to demonstrate advantages with respect to the failure pattern and survival. Development of new treatment strategy in combining IFRT and chemotherapy is required for improving outcomes.

  12. Insights to the effects of free cells on community structure of attached cells and chalcopyrite bioleaching during different stages.

    Science.gov (United States)

    Feng, Shoushuai; Yang, Hailin; Wang, Wu

    2016-01-01

    The effects of free cells on community structure of attached cells and chalcopyrite bioleaching by Acidithiobacillus sp. during different stages were investigated. The attached cells of Acidithiobacillus thiooxidans owned the community advantage from 14thd to the end of bioprocess in the normal system. The community structure of attached cells was greatly influenced in the free cells-deficient systems. Compared to A. thiooxidans, the attached cells community of Acidithiobacillus ferrooxidans had a higher dependence on its free cells. Meanwhile, the analysis of key biochemical parameters revealed that the effects of free cells on chalcopyrite bioleaching in different stages were diverse, ranging from 32.8% to 64.3%. The bioleaching contribution of free cells of A. ferrooxidans in the stationary stage (8-14thd) was higher than those of A. thiooxidans, while the situation was gradually reversed in the jarosite passivation inhibited stage (26-40thd). These results may be useful in guiding chalcopyrite bioleaching. PMID:26492170

  13. INTEGRATED GASIFICATION COMBINED CYCLE PROJECT 2 MW FUEL CELL DEMONSTRATION

    Energy Technology Data Exchange (ETDEWEB)

    FuelCell Energy

    2005-05-16

    With about 50% of power generation in the United States derived from coal and projections indicating that coal will continue to be the primary fuel for power generation in the next two decades, the Department of Energy (DOE) Clean Coal Technology Demonstration Program (CCTDP) has been conducted since 1985 to develop innovative, environmentally friendly processes for the world energy market place. The 2 MW Fuel Cell Demonstration was part of the Kentucky Pioneer Energy (KPE) Integrated Gasification Combined Cycle (IGCC) project selected by DOE under Round Five of the Clean Coal Technology Demonstration Program. The participant in the CCTDP V Project was Kentucky Pioneer Energy for the IGCC plant. FuelCell Energy, Inc. (FCE), under subcontract to KPE, was responsible for the design, construction and operation of the 2 MW fuel cell power plant. Duke Fluor Daniel provided engineering design and procurement support for the balance-of-plant skids. Colt Engineering Corporation provided engineering design, fabrication and procurement of the syngas processing skids. Jacobs Applied Technology provided the fabrication of the fuel cell module vessels. Wabash River Energy Ltd (WREL) provided the test site. The 2 MW fuel cell power plant utilizes FuelCell Energy's Direct Fuel Cell (DFC) technology, which is based on the internally reforming carbonate fuel cell. This plant is capable of operating on coal-derived syngas as well as natural gas. Prior testing (1992) of a subscale 20 kW carbonate fuel cell stack at the Louisiana Gasification Technology Inc. (LGTI) site using the Dow/Destec gasification plant indicated that operation on coal derived gas provided normal performance and stable operation. Duke Fluor Daniel and FuelCell Energy developed a commercial plant design for the 2 MW fuel cell. The plant was designed to be modular, factory assembled and truck shippable to the site. Five balance-of-plant skids incorporating fuel processing, anode gas oxidation, heat recovery

  14. Regulation of the G1 phase of the mammalian cell cycle

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In any multi-cellular organism, the balance between cell division and cell death maintains a constant cell num ber. Both cell division cycle and cell death are highly regulated events. Whether the cell will proceed through the cycle or not, depends upon whether the conditions re quired at the checkpoints during the cycle are filfilled. In higher eucaryotic cells, such as mammalian cells, signals that arrest the cycle usually act at a G1 checkpoint. Cells that pass this restriction point are committed to complete the cycle. Regulation of the G1 phase of the cell cycle is extremely complex and involves many different families of proteins such as retinoblastoma family, cyclin dependent kinases, cyclins, and cyclin kinase inhibitors.

  15. Analysis of X-ray induced cell-cycle perturbations in mouse osteosarcoma cells: a two-signal cell-cycle model

    International Nuclear Information System (INIS)

    The effects of X-irradiation on mouse osteosarcoma cells have been studied by time-lapse cinematography and the resulting pedigrees have been analysed statistically. It is shown that the irradiation treatment causes three types of cell kinetic lesions: cell death (disintegration), cell sterilization (failure to divide) and proliferation delay. The first two lesions are the most important with regard to survival of the irradiated cell in a clonal assay. Of these two lesions, sterilization appears to be highly correlated for sister cells, while this is not true for cell disintegration. This indicates that cell survival in a clonal assay may be a function of the ratio of the incidences of these two types of lesions. The X-ray-induced proliferation delay was studied in terms of intermitotic time distributions, mother-daughter correlation and sibling correlation in relation to the current cell-cycle phase at the time of treatment. This analysis shows that the effects of irradiation on these cell-cycle characteristics is highly cell-cycle-dependent. A qualitative model to account for the observations is presented. (author)

  16. Energy analysis of two stage packed-bed chemical looping combustion configurations for integrated gasification combined cycles

    International Nuclear Information System (INIS)

    Chemical looping combustion is a promising technology for power production with integrated CO2 capture. High overall efficiencies can be reached, if the CLC reactors are operated at elevated pressures and high temperature, which can be accommodated in packed bed reactors. More possible oxygen carriers can be selected if the desired temperature rise for power production is achieved in a two stage chemical looping combustion (TS-CLC) process. In this work, the TS-CLC configuration using copper and manganese based oxygen carriers has been integrated in a complete power plant based on coal gasification (IG-CLC). An extensive energy analysis based on the combined use of a packed bed reactor modeling tool and a complete process simulation has been undertaken. An economic estimation of the reactors capital cost has also been carried out. From the material and energy balances the IG-CLC with one stage nickel-based CLC process results in a net electric efficiency of 41.1% on low heating value basis. In case of TS-CLC, efficiencies of 40.3%–40.8% have been obtained. This demonstrated that IGCC (integrated gasification combined cycles) adopting a TS-CLC process can also achieve high efficiency compared to conventional CO2 capture technologies. Although a larger reactor volume is required for TS-CLC, the total estimated investment costs are a factor two lower, because the oxygen carriers are much cheaper. - Highlights: • Complete IG-CLC power plants have been evaluated for different CLC configurations. • Novel operation strategy for the TS-CLC has been proposed: TS-CLC parallel. • The estimated capital costs of TS-CLC are a factor two smaller than one stage CLC. • The process efficiency of TS-CLC is demonstrated to be close to the one stage CLC

  17. Clinical and surgical-pathological staging in early non-small cell lung cancer

    OpenAIRE

    Ioannis Koukis; Ioannis Gkiozos; Ioannis Ntanos; Elias Kainis; Konstantinos N. Syrigos

    2013-01-01

    Staging is of the utmost importance in the evaluation of a patient with non-small cell lung cancer (NSCLC) because it defines the actual extent of the disease. Accurate staging allows multidisciplinary oncology teams to plan the best surgical or medical treatment and to predict patient prognosis. Based on the recommendation of the International Association for the Study of Lung Cancer (IASLC), a tumor, node, and metastases (TNM) staging system is currently used for NSCLC. Clinical staging (c-...

  18. Robust synchronization of coupled circadian and cell cycle oscillators in single mammalian cells.

    Science.gov (United States)

    Bieler, Jonathan; Cannavo, Rosamaria; Gustafson, Kyle; Gobet, Cedric; Gatfield, David; Naef, Felix

    2014-01-01

    Circadian cycles and cell cycles are two fundamental periodic processes with a period in the range of 1 day. Consequently, coupling between such cycles can lead to synchronization. Here, we estimated the mutual interactions between the two oscillators by time-lapse imaging of single mammalian NIH3T3 fibroblasts during several days. The analysis of thousands of circadian cycles in dividing cells clearly indicated that both oscillators tick in a 1:1 mode-locked state, with cell divisions occurring tightly 5 h before the peak in circadian Rev-Erbα-YFP reporter expression. In principle, such synchrony may be caused by either unidirectional or bidirectional coupling. While gating of cell division by the circadian cycle has been most studied, our data combined with stochastic modeling unambiguously show that the reverse coupling is predominant in NIH3T3 cells. Moreover, temperature, genetic, and pharmacological perturbations showed that the two interacting cellular oscillators adopt a synchronized state that is highly robust over a wide range of parameters. These findings have implications for circadian function in proliferative tissues, including epidermis, immune cells, and cancer. PMID:25028488

  19. Effect of Docosahexaenoic Acid on Cell Cycle Pathways in Breast Cell Lines With Different Transformation Degree.

    Science.gov (United States)

    Rescigno, Tania; Capasso, Anna; Tecce, Mario Felice

    2016-06-01

    n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), abundant in fish, have been shown to affect development and progression of some types of cancer, including breast cancer. The aim of our study was to further analyze and clarify the effects of these nutrients on the molecular mechanisms underlying breast cancer. Following treatments with DHA we examined cell viability, death, cell cycle, and some molecular effects in breast cell lines with different transformation, phenotypic, and biochemical characteristics (MCF-10A, MCF-7, SK-BR-3, ZR-75-1). These investigations showed that DHA is able to affect cell viability, proliferation, and cell cycle progression in a different way in each assayed breast cell line. The activation of ERK1/2 and STAT3 pathways and the expression and/or activation of molecules involved in cell cycle regulation such as p21(Waf1/Cip1) and p53, are very differently regulated by DHA treatments in each cell model. DHA selectively: (i) arrests non tumoral MCF-10A breast cells in G0 /G1 cycle phase, activating p21(Waf1/Cip1) , and p53, (ii) induces to death highly transformed breast cells SK-BR-3, reducing ERK1/2 and STAT3 phosphorylation and (iii) only slightly affects each analyzed process in MCF-7 breast cell line with transformation degree lower than SK-BR-3 cells. These findings suggest a more relevant inhibitory role of DHA within early development and late progression of breast cancer cell transformation and a variable effect in the other phases, depending on individual molecular properties and degree of malignancy of each clinical case. J. Cell. Physiol. 231: 1226-1236, 2016. © 2015 Wiley Periodicals, Inc. PMID:26480024

  20. Identification of Cell Cycle Dependent Interaction Partners of the Septins by Quantitative Mass Spectrometry.

    Science.gov (United States)

    Renz, Christian; Oeljeklaus, Silke; Grinhagens, Sören; Warscheid, Bettina; Johnsson, Nils; Gronemeyer, Thomas

    2016-01-01

    The septins are a conserved family of GTP-binding proteins that, in the baker's yeast, assemble into a highly ordered array of filaments at the mother bud neck. These filaments undergo significant structural rearrangements during the cell cycle. We aimed at identifying key components that are involved in or regulate the transitions of the septins. By combining cell synchronization and quantitative affinity-purification mass-spectrometry, we performed a screen for specific interaction partners of the septins at three distinct stages of the cell cycle. A total of 83 interaction partners of the septins were assigned. Surprisingly, we detected DNA-interacting/nuclear proteins and proteins involved in ribosome biogenesis and protein synthesis predominantly present in alpha-factor arrested that do not display an assembled septin structure. Furthermore, two distinct sets of regulatory proteins that are specific for cells at S-phase with a stable septin collar or at mitosis with split septin rings were identified. Complementary methods like SPLIFF and immunoprecipitation allowed us to more exactly define the spatial and temporal characteristics of selected hits of the AP-MS screen. PMID:26871441

  1. Ghrelin regulates cell cycle-related gene expression in cultured hippocampal neural stem cells.

    Science.gov (United States)

    Chung, Hyunju; Park, Seungjoon

    2016-08-01

    We have previously demonstrated that ghrelin stimulates the cellular proliferation of cultured adult rat hippocampal neural stem cells (NSCs). However, little is known about the molecular mechanisms by which ghrelin regulates cell cycle progression. The purpose of this study was to investigate the potential effects of ghrelin on cell cycle regulatory molecules in cultured hippocampal NSCs. Ghrelin treatment increased proliferation assessed by CCK-8 proliferation assay. The expression levels of proliferating cell nuclear antigen and cell division control 2, well-known cell-proliferating markers, were also increased by ghrelin. Fluorescence-activated cell sorting analysis revealed that ghrelin promoted progression of cell cycle from G0/G1 to S phase, whereas this progression was attenuated by the pretreatment with specific inhibitors of MEK/extracellular signal-regulated kinase 1/2, phosphoinositide 3-kinase/Akt, mammalian target of rapamycin, and janus kinase 2/signal transducer and activator of transcription 3. Ghrelin-induced proliferative effect was associated with increased expression of E2F1 transcription factor in the nucleus, as determined by Western blotting and immunofluorescence. We also found that ghrelin caused an increase in protein levels of positive regulators of cell cycle, such as cyclin A and cyclin-dependent kinase (CDK) 2. Moreover, p27(KIP1) and p57(KIP2) protein levels were reduced when cell were exposed to ghrelin, suggesting downregulation of CDK inhibitors may contribute to proliferative effect of ghrelin. Our data suggest that ghrelin targets both cell cycle positive and negative regulators to stimulate proliferation of cultured hippocampal NSCs. PMID:27325242

  2. Loratadine dysregulates cell cycle progression and enhances the effect of radiation in human tumor cell lines

    Directory of Open Access Journals (Sweden)

    Cook John A

    2010-02-01

    Full Text Available Abstract Background The histamine receptor-1 (H1-antagonist, loratadine has been shown to inhibit growth of human colon cancer xenografts in part due to cell cycle arrest in G2/M. Since this is a radiation sensitive phase of the cell cycle, we sought to determine if loratadine modifies radiosensitivity in several human tumor cell lines with emphasis on human colon carcinoma (HT29. Methods Cells were treated with several doses of loratadine at several time points before and after exposure to radiation. Radiation dose modifying factors (DMF were determined using full radiation dose response survival curves. Cell cycle phase was determined by flow cytometry and the expression of the cell cycle-associated proteins Chk1, pChk1ser345, and Cyclin B was analyzed by western blot. Results Loratadine pre-treatment of exponentially growing cells (75 μM, 24 hours increased radiation-induced cytotoxicity yielding a radiation DMF of 1.95. However, treatment of plateau phase cells also yielded a DMF of 1.3 suggesting that mechanisms other than cell cycle arrest also contribute to loratadine-mediated radiation modification. Like irradiation, loratadine initially induced G2/M arrest and activation of the cell-cycle associated protein Chk1 to pChk1ser345, however a subsequent decrease in expression of total Chk1 and Cyclin B correlated with abrogation of the G2/M checkpoint. Analysis of DNA repair enzyme expression and DNA fragmentation revealed a distinct pattern of DNA damage in loratadine-treated cells in addition to enhanced radiation-induced damage. Taken together, these data suggest that the observed effects of loratadine are multifactorial in that loratadine 1 directly damages DNA, 2 activates Chk1 thereby promoting G2/M arrest making cells more susceptible to radiation-induced DNA damage and, 3 downregulates total Chk1 and Cyclin B abrogating the radiation-induced G2/M checkpoint and allowing cells to re-enter the cell cycle despite the persistence of

  3. DNA Damage, Cell Cycle Arrest, and Apoptosis Induction Caused by Lead in Human Leukemia Cells.

    Science.gov (United States)

    Yedjou, Clement G; Tchounwou, Hervey M; Tchounwou, Paul B

    2016-01-01

    In recent years, the industrial use of lead has been significantly reduced from paints and ceramic products, caulking, and pipe solder. Despite this progress, lead exposure continues to be a significant public health concern. The main goal of this research was to determine the in vitro mechanisms of lead nitrate [Pb(NO₃)₂] to induce DNA damage, apoptosis, and cell cycle arrest in human leukemia (HL-60) cells. To reach our goal, HL-60 cells were treated with different concentrations of Pb(NO₃)₂ for 24 h. Live cells and necrotic death cells were measured by the propidium idiode (PI) assay using the cellometer vision. Cell apoptosis was measured by the flow cytometry and DNA laddering. Cell cycle analysis was evaluated by the flow cytometry. The result of the PI demonstrated a significant (p rupture by Pb(NO₃)₂ compared to the control. Data generated from the comet assay indicated a concentration-dependent increase in DNA damage, showing a significant increase (p < 0.05) in comet tail-length and percentages of DNA cleavage. Data generated from the flow cytometry assessment indicated that Pb(NO₃)₂ exposure significantly (p < 0.05) increased the proportion of caspase-3 positive cells (apoptotic cells) compared to the control. The flow cytometry assessment also indicated Pb(NO₃)₂ exposure caused cell cycle arrest at the G₀/G₁ checkpoint. The result of DNA laddering assay showed presence of DNA smear in the agarose gel with little presence of DNA fragments in the treated cells compared to the control. In summary, Pb(NO₃)₂ inhibits HL-60 cells proliferation by not only inducing DNA damage and cell cycle arrest at the G₀/G₁ checkpoint but also triggering the apoptosis through caspase-3 activation and nucleosomal DNA fragmentation accompanied by secondary necrosis. We believe that our study provides a new insight into the mechanisms of Pb(NO₃)₂ exposure and its associated adverse health effects. PMID:26703663

  4. Timing robustness in the budding and fission yeast cell cycles.

    KAUST Repository

    Mangla, Karan

    2010-02-01

    Robustness of biological models has emerged as an important principle in systems biology. Many past analyses of Boolean models update all pending changes in signals simultaneously (i.e., synchronously), making it impossible to consider robustness to variations in timing that result from noise and different environmental conditions. We checked previously published mathematical models of the cell cycles of budding and fission yeast for robustness to timing variations by constructing Boolean models and analyzing them using model-checking software for the property of speed independence. Surprisingly, the models are nearly, but not totally, speed-independent. In some cases, examination of timing problems discovered in the analysis exposes apparent inaccuracies in the model. Biologically justified revisions to the model eliminate the timing problems. Furthermore, in silico random mutations in the regulatory interactions of a speed-independent Boolean model are shown to be unlikely to preserve speed independence, even in models that are otherwise functional, providing evidence for selection pressure to maintain timing robustness. Multiple cell cycle models exhibit strong robustness to timing variation, apparently due to evolutionary pressure. Thus, timing robustness can be a basis for generating testable hypotheses and can focus attention on aspects of a model that may need refinement.

  5. Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle

    Directory of Open Access Journals (Sweden)

    Shunsuke Nojiri

    2014-03-01

    Full Text Available Many investigations have revealed that a low recurrence rate of hepatocellular carcinoma (HCC is associated with high serum albumin levels in patients; therefore, high levels of serum albumin are a major indicator of a favorable prognosis. However, the mechanism inhibiting the proliferation of HCC has not yet been elucidated, so we investigated the effect of serum albumin on HCC cell proliferation. Hep3B was cultured in MEM with no serum or containing 5 g/dL human albumin. As control samples, Prionex was added to generate the same osmotic pressure as albumin. After 24-h incubation, the expressions of α-fetoprotein (AFP, p53, p21, and p57 were evaluated with real-time PCR using total RNA extracted from the liver. Protein expressions and the phosphorylation of Rb (retinoblastoma were determined by Western blot analysis using total protein extracted from the liver. For flow cytometric analysis of the cell cycle, FACS analysis was performed. The percentages of cell cycle distribution were evaluated by PI staining, and all samples were analyzed employing FACScalibur (BD with appropriate software (ModFit LT; BD. The cell proliferation assay was performed by counting cells with using a Scepter handy automated cell counter (Millipore. The mRNA levels of AFP relative to Alb(−: Alb(−, Alb(+, and Prionex, were 1, 0.7 ± 0.2 (p < 0.001 for Alb(−, and 1 ± 0.3, respectively. The mRNA levels of p21 were 1, 1.58 ± 0.4 (p = 0.007 for Alb(− and p = 0.004 for Prionex, and 0.8 ± 0.2, respectively. The mRNA levels of p57 were 1, 4.4 ± 1.4 (p = 0.002 for Alb(− and Prionex, and 1.0 ± 0.1, respectively. The protein expression levels of Rb were similar in all culture media. The phosphorylation of P807/811 and P780 of Rb protein was reduced in Alb(+. More cells in the G0/G1 phase and fewer cells in S and G2/M phases were obtained in Alb(+ than in Alb(− (G0/G1: 60.9%, 67.7%, 61.5%; G2/M: 16.5%, 13.1%, 15.6%; S: 22.6%, 19.2%, 23.0%, Alb(−, Alb

  6. New chlorogenin hexasaccharide isolated from Agave fourcroydes with cytotoxic and cell cycle inhibitory activities.

    Science.gov (United States)

    Ohtsuki, Takashi; Koyano, Takashi; Kowithayakorn, Thaworn; Sakai, Shinobu; Kawahara, Nobuo; Goda, Yukihiro; Yamaguchi, Naoto; Ishibashi, Masami

    2004-07-15

    A new chlorogenin hexasaccharide (1) was isolated from leaves of Agave fourcroydes (Agavaceae). The structure of the new saponin was elucidated as chlorogenin 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl-(1-->2)]-beta-D-glucopyranosyl-(1-->4)-beta-D-galactopyranoside] (1) by spectroscopic analysis and the result of acidic hydrolysis. The new saponin (1) as well as known hexasaccharides (3 and 5) isolated here showed cytotoxicity against HeLa cells, and 1 exhibited a cell cycle inhibitory effect at the G2/M stage at the concentration of 7.5 and 10 microg/mL. PMID:15210151

  7. Clinical outcome of concurrent chemo-radiotherapy for patients with stage IV non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To analyze the clinical outcome of concurrent chemo-radiotherapy in stage IV non-small cell lung cancer(NSCLC). Methods: From Jan. 1997 to Dec. 2006, 214 patients with pathologically or cytologically proven stage IV NSCLC were included in this analysis. Of those patients, 98 received radiotherapy concurrently with 3-week cycle chemotherapy (group A), 18 received radiotherapy concurrently with weekly chemotherapy( group B), 44 received chemotherapy alone, 37 received radiotherapy alone and 13 received sequential chemo-radiotherapy. The primary tumor was treated by three-dimensional conformal radiotherapy(3DCRT) or conventional radiotherapy with conventional fractionation or late-course accelerated hyperfraction (LAHRT). Group A received 21-28 days cycle cisplatin-based chemotherapy (cisplatin combined with PTX, DTY, NVB or Vp-16), and group B received weekly DDP combined with PTX or toptecon for 4-6 weeks. Results: The follow-up rate was 99%. The 1- and 2-year overall survival rates of group A, group B, chemotherapy alone, radiotherapy alone and sequential chemo-radiotherapy were 41% and 11%, 16% and 0, 31% and 7%, 34% and 10%, 26% and 3%, respectively(χ2=11.18, P=0.025). The patients with concurrent 3DCRT, LAHRT and radiotherapy dose ≥70 Gy had better survival in group A than those in chemotherapy alone group. Patients who received ≥2 cycles chemotherapy with concurrent radio-therapy had longer survival time than those who had ≥2 cycles chemotherapy alone. Conclusions: Concurrent chemotherapy and 3 DCRT, LAHRT with the dose ≥70 Gy can improve the overall survival of patients with stage IV non-small cell lung cancer. (authors)

  8. Uranium Determination in Samples from Decommissioning of Nuclear facilities Related to the First Stage of Nuclear Fuel Cycle

    International Nuclear Information System (INIS)

    An adequate workplace monitoring must be carried out during the decommissioning activities, to ensure the protection of workers involved in these tasks. In addition, a large amount of waste materials are generated during the decommissioning of nuclear facilities. Clearance levels are established by regulatory authorities and are normally quite low. The determination of those activity concentration levels become more difficult when it is necessary to quantify alpha emitters such as uranium, especially when complex matrices are involved. Several methods for uranium determination in samples obtained during the decommissioning of a facility related to the first stage of the nuclear fuel cycle are presented in this work. Measurements were carried out by laboratory techniques. In situ gamma spectrometry was also used to perform measurements on site. A comparison among the different techniques was also done by analysing the results obtained in some practical applications. (Author)

  9. Uranium determination in samples from decommissioning of nuclear facilities related to the first stage of the nuclear fuel cycle

    International Nuclear Information System (INIS)

    Large amounts of waste materials are generated during the decommissioning of nuclear facilities. Clearance levels are established by regulatory authorities and are normally quite low. Determination of those activity concentration levels becomes more difficult when it is necessary to quantify alpha emitters such as uranium, especially when complex matrixes are involved. In addition, an adequate workplace monitoring must be carried out during the decommissioning activities, to ensure the protection of workers involved in these tasks. Several methods for uranium determination in samples obtained during the decommissioning of a facility related to the first stage of the nuclear fuel cycle are presented in this work. According to the kind and sample size, together with the minimum detectable activity (MDA) that must be reached in each case, measurements were carried out by laboratory and 'in situ' gamma spectrometry, as well as by alpha spectrometry. A comparison among the different techniques was also performed by analysing the results obtained in some practical applications

  10. Uranium determination in samples from decommissioning of nuclear facilities related to the first stage of the nuclear fuel cycle

    Science.gov (United States)

    Alvarez; Correa; Navarro; Sancho

    2000-07-01

    Large amounts of waste materials are generated during the decommissioning of nuclear facilities. Clearance levels are established by regulatory authorities and are normally quite low. Determination of those activity concentration levels becomes more difficult when it is necessary to quantify alpha emitters such as uranium, especially when complex matrixes are involved. In addition, an adequate workplace monitoring must be carried out during the decommissioning activities, to ensure the protection of workers involved in these tasks. Several methods for uranium determination in samples obtained during the decommissioning of a facility related to the first stage of the nuclear fuel cycle are presented in this work. According to the kind and sample size, together with the minimum detectable activity (MDA) that must be reached in each case, measurements were carried out by laboratory and 'in situ' gamma spectrometry, as well as by alpha spectrometry. A comparison among the different techniques was also performed by analysing the results obtained in some practical applications. PMID:10879885

  11. Gold nanoparticle sensitize radiotherapy of prostate cancer cells by regulation of the cell cycle

    Science.gov (United States)

    Roa, Wilson; Zhang, Xiaojing; Guo, Linghong; Shaw, Andrew; Hu, Xiuying; Xiong, Yeping; Gulavita, Sunil; Patel, Samir; Sun, Xuejun; Chen, Jie; Moore, Ronald; Xing, James Z.

    2009-09-01

    Glucose-capped gold nanoparticles (Glu-GNPs) have been used to improve cellular targeting and radio-sensitization. In this study, we explored the mechanism of Glu-GNP enhanced radiation sensitivity in radiation-resistant human prostate cancer cells. Cell survival and proliferation were measured using MTT and clonogenic assay. Flow cytometry with staining by propidium iodide (PI) was performed to study the cell cycle changes induced by Glu-GNPs, and western blotting was used to determine the expression of p53 and cyclin proteins that correlated to cell cycle regulation. With 2 Gy of ortho-voltage irradiation, Glu-GNP showed a 1.5-2.0 fold enhancement in growth inhibition when compared to x-rays alone. Comparing the cell cycle change, Glu-GNPs induced acceleration in the G0/G1 phase and accumulation of cells in the G2/M phase at 29.8% versus 18.4% for controls at 24 h. G2/M arrest was accompanied by decreased expression of p53 and cyclin A, and increased expression of cyclin B1 and cyclin E. In conclusion, Glu-GNPs trigger activation of the CDK kinases leading to cell cycle acceleration in the G0/G1 phase and accumulation in the G2/M phase. This activation is accompanied by a striking sensitization to ionizing radiation, which may have clinical implications.

  12. Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Jing Wang; Xiao-Wen Lv; Jie-Ping Shi; Xiao-Song Hu

    2007-01-01

    AIM:To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells.Possible molecular mechanisms were explored.METHODS:[3-(4,5)-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide(MTT)assay,plasmid transfection,reporter assay,FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells.RESULTS:C2-ceramide was found to inhibit the growth of Bel7402 cells by inducing cell cycle arrest.During the process,the expression of p21 protein increased,while that of cyclinD1,phospho-ERK1/2 and c-myc decreased.Furthermore,the level of CDK7 was downregulated,while the transcriptional activity of PPARγ was upregulated.Addition of GW9662,which is a PPARγ specific antagonist,could reserve the modulation action on CDK7.CONCLUSION:Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7,at least partly,through PPARγ activation.The ERK signaling pathway was involved in this process.

  13. Stages of Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key Points Non- ...

  14. Treatment Options by Stage (Small Cell Lung Cancer)

    Science.gov (United States)

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  15. Treatment Options by Stage (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key Points Non- ...

  16. Cell cycle arrest and apoptosis, two alternative mechanisms for PMKT2 killer activity.

    Science.gov (United States)

    Santos, Antonio; Alonso, Alejandro; Belda, Ignacio; Marquina, Domingo

    2013-01-01

    Pichia membranifaciens CYC 1086 secretes a unique 30kDa killer toxin (PMKT2) that inhibits a variety of spoilage yeasts and fungi of agronomical interest. The cytocidal effect of PMKT2 on Saccharomyces cerevisiae cells was studied. Metabolic events associated with the loss of S. cerevisiae viability caused by PMKT2 were qualitatively identical to those reported for K28 killer toxin activity, but different to those reported for PMKT. At higher doses, none of the cellular events accounting for the action of PMKT, the killer toxin secreted by P. membranifaciens CYC 1106, was observed for PMKT2. Potassium leakage, sodium influx and the decrease of intracellular pH were not among the primary effects of PMKT2. We report here that this protein is unable to form ion-permeable channels in liposome membranes, suggesting that channel formation is not the mechanism of cytotoxic action of PMKT2. Nevertheless, flow cytometry studies have revealed a cell cycle arrest at an early S-phase with an immature bud and pre-replicated 1n DNA content. By testing the sensitivity of cells arrested at different stages in the cell cycle, we hoped to identify the execution point for lethality more precisely. Cells arrested at the G1-phase by α-factor or arrested at G2-phase by the spindle poison methyl benzimidazol-2-yl-carbamate (MBC) were protected against the toxin. Cells released from the arrest in both cases were killed by PMKT2 at a similar rate. Nevertheless, cells released from MBC-arrest were able to grow for a short time, and then viability dropped rapidly. These findings suggest that cells released from G2-phase are initially able to divide, but die in the presence of PMKT2 after initiating the S-phase in a new cycle, adopting a terminal phenotype within that cycle. By contrast, low doses of PMKT and PMKT2 were able to generate the same cellular response. The evidence presented here shows that treating yeast with low doses of PMKT2 leads to the typical membranous, cytoplasmic

  17. Tcf3 and cell cycle factors contribute to butyrate resistance in colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Chiaro, Christopher, E-mail: cchiaro@tcmedc.org [Department of Basic Sciences, The Commonwealth Medical College, 525 Pine Street, Scranton, PA 18509 (United States); Lazarova, Darina L., E-mail: dlazarova@tcmedc.org [Department of Basic Sciences, The Commonwealth Medical College, 525 Pine Street, Scranton, PA 18509 (United States); Bordonaro, Michael, E-mail: mbordonaro@tcmedc.org [Department of Basic Sciences, The Commonwealth Medical College, 525 Pine Street, Scranton, PA 18509 (United States)

    2012-11-09

    Highlights: Black-Right-Pointing-Pointer We investigate mechanisms responsible for butyrate resistance in colon cancer cells. Black-Right-Pointing-Pointer Tcf3 modulates butyrate's effects on Wnt activity and cell growth in resistant cells. Black-Right-Pointing-Pointer Tcf3 modulation of butyrate's effects differ by cell context. Black-Right-Pointing-Pointer Cell cycle factors are overexpressed in the resistant cells. Black-Right-Pointing-Pointer Reversal of altered gene expression can enhance the anti-cancer effects of butyrate. -- Abstract: Butyrate, a fermentation product of dietary fiber, inhibits clonal growth in colorectal cancer (CRC) cells dependent upon the fold induction of Wnt activity. We have developed a CRC cell line (HCT-R) that, unlike its parental cell line, HCT-116, does not respond to butyrate exposure with hyperactivation of Wnt signaling and suppressed clonal growth. PCR array analyses revealed Wnt pathway-related genes, the expression of which differs between butyrate-sensitive HCT-116 CRC cells and their butyrate-resistant HCT-R cell counterparts. We identified overexpression of Tcf3 as being partially responsible for the butyrate-resistant phenotype, as this DNA-binding protein suppresses the hyperinduction of Wnt activity by butyrate. Consequently, Tcf3 knockdown in HCT-R cells restores their sensitivity to the effects of butyrate on Wnt activity and clonal cell growth. Interestingly, the effects of overexpressed Tcf3 differ between HCT-116 and HCT-R cells; thus, in HCT-116 cells Tcf3 suppresses proliferation without rendering the cells resistant to butyrate. In HCT-R cells, however, the overexpression of Tcf3 inhibits Wnt activity, and the cells are still able to proliferate due to the higher expression levels of cell cycle factors, particularly those driving the G{sub 1} to S transition. Knowledge of the molecular mechanisms determining the variable sensitivity of CRC cells to butyrate may assist in developing approaches that

  18. Tcf3 and cell cycle factors contribute to butyrate resistance in colorectal cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► We investigate mechanisms responsible for butyrate resistance in colon cancer cells. ► Tcf3 modulates butyrate’s effects on Wnt activity and cell growth in resistant cells. ► Tcf3 modulation of butyrate’s effects differ by cell context. ► Cell cycle factors are overexpressed in the resistant cells. ► Reversal of altered gene expression can enhance the anti-cancer effects of butyrate. -- Abstract: Butyrate, a fermentation product of dietary fiber, inhibits clonal growth in colorectal cancer (CRC) cells dependent upon the fold induction of Wnt activity. We have developed a CRC cell line (HCT-R) that, unlike its parental cell line, HCT-116, does not respond to butyrate exposure with hyperactivation of Wnt signaling and suppressed clonal growth. PCR array analyses revealed Wnt pathway-related genes, the expression of which differs between butyrate-sensitive HCT-116 CRC cells and their butyrate-resistant HCT-R cell counterparts. We identified overexpression of Tcf3 as being partially responsible for the butyrate-resistant phenotype, as this DNA-binding protein suppresses the hyperinduction of Wnt activity by butyrate. Consequently, Tcf3 knockdown in HCT-R cells restores their sensitivity to the effects of butyrate on Wnt activity and clonal cell growth. Interestingly, the effects of overexpressed Tcf3 differ between HCT-116 and HCT-R cells; thus, in HCT-116 cells Tcf3 suppresses proliferation without rendering the cells resistant to butyrate. In HCT-R cells, however, the overexpression of Tcf3 inhibits Wnt activity, and the cells are still able to proliferate due to the higher expression levels of cell cycle factors, particularly those driving the G1 to S transition. Knowledge of the molecular mechanisms determining the variable sensitivity of CRC cells to butyrate may assist in developing approaches that prevent or reverse butyrate resistance.

  19. SPARC expression induces cell cycle arrest via STAT3 signaling pathway in medulloblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Chetty, Chandramu [Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL-61605 (United States); Dontula, Ranadheer [Section of Hematology/Oncology, Department of Medicine, University of Illinois College of Medicine at Chicago, 840 South Wood Street, Suite 820-E, Chicago, IL-60612 (United States); Ganji, Purnachandra Nagaraju [Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL-61605 (United States); Gujrati, Meena [Department of Pathology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL-61605 (United States); Lakka, Sajani S., E-mail: slakka@uic.edu [Section of Hematology/Oncology, Department of Medicine, University of Illinois College of Medicine at Chicago, 840 South Wood Street, Suite 820-E, Chicago, IL-60612 (United States)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Ectopic expression of SPARC impaired cell proliferation in medulloblastoma cells. Black-Right-Pointing-Pointer SPARC expression induces STAT3 mediated cell cycle arrest in medulloblastoma cells. Black-Right-Pointing-Pointer SPARC expression significantly inhibited pre-established tumor growth in nude-mice. -- Abstract: Dynamic cell interaction with ECM components has profound influence in cancer progression. SPARC is a component of the ECM, impairs the proliferation of different cell types and modulates tumor cell aggressive features. We previously reported that SPARC expression significantly impairs medulloblastoma tumor growth in vivo. In this study, we demonstrate that expression of SPARC inhibits medulloblastoma cell proliferation. MTT assay indicated a dose-dependent reduction in tumor cell proliferation in adenoviral mediated expression of SPARC full length cDNA (Ad-DsRed-SP) in D425 and UW228 cells. Flow cytometric analysis showed that Ad-DsRed-SP-infected cells accumulate in the G2/M phase of cell cycle. Further, immunoblot and immunoprecipitation analyses revealed that SPARC induced G2/M cell cycle arrest was mediated through inhibition of the Cyclin-B-regulated signaling pathway involving p21 and Cdc2 expression. Additionally, expression of SPARC decreased STAT3 phosphorylation at Tyr-705; constitutively active STAT3 expression reversed SPARC induced G2/M arrest. Ad-DsRed-SP significantly inhibited the pre-established orthotopic tumor growth and tumor volume in nude-mice. Immunohistochemical analysis of tumor sections from mice treated with Ad-DsRed-SP showed decreased immunoreactivity for pSTAT3 and increased immunoreactivity for p21 compared to tumor section from mice treated with mock and Ad-DsRed. Taken together our studies further reveal that STAT3 plays a key role in SPARC induced G2/M arrest in medulloblastoma cells. These new findings provide a molecular basis for the mechanistic understanding of the

  20. S-phase-dependent cell cycle disturbances caused by Aleutian mink disease parvovirus

    DEFF Research Database (Denmark)

    Oleksiewicz, M.B.; Alexandersen, Søren

    1997-01-01

    We examined replication of the autonomous parovirus Aleutian mink disease parovirus (ADV) in relation to cell cycle progression of permissive Crandell feline kidney (CRFK) cells. Flow cytometric analysis showed that ADV caused a composite, binary pattern of cell cycle arrest. ADV-induced cell cyc...

  1. Inhibition of cell cycle progression by penta-acetyl geniposide in rat C6 glioma cells

    International Nuclear Information System (INIS)

    Penta-acetyl geniposide, (Ac)5-GP, the acetylated compound of geniposide, is able to inhibit the growth of rat C6 glioma cells in culture and in the bearing rats. Our recent data indicated that the induction of cell apoptosis and cell cycle arrest at G0/gap phase 1 (G1) by (Ac)5-GP might be associated with the induction of p53 and c-Myc, and mediated via the apoptosis-related bcl-2 family proteins. In this report, we further investigated the mechanism involved in the cell cycle arrest induced by (Ac)5-GP in C6 glioma cells. The inhibitory effect of (Ac)5-GP on the cell cycle progression of C6 glioma cells which arrested cells at the G0/G1 phase was associated with a marked decrease in the protein expression of cyclin D1, and an induction in the content of cyclin-dependent kinase (cdk) inhibitor p21 protein. This effect was correlated with the elevation in p53 levels. Further immunoprecipitation studies found that, in response to the treatment, the formation of cyclin D1/cdk 4 complex declined, preventing the phosphorylation of retinoblastoma (Rb) and the subsequent dissociation of Rb/E2F complex. These results illustrated that the apoptotic effect of (Ac)5-GP, arresting cells at the G0/G1 phase, was exerted by inducing the expression of p21 that, in turn, repressed the activity of cyclin D1/cdk 4 and the phosphorylation of Rb

  2. Change of the cell cycle after flutamide treatment in prostate cancer cells and its molecular mechanism

    Institute of Scientific and Technical Information of China (English)

    Yong Wang; Wei-Jun Qin; He Wang; Guo-Xing Shao; Chen Shao; Chang-Hong Shi; Lei Zhang; Hong-Hong Yue; Peng-Fei Wang; Bo Yang; Yun-Tao Zhang; Fan Liu

    2005-01-01

    Aim: To explore the effect of androgen receptor (AR) on the expression of the cell cycle-related genes, such as CDKN1A and BTG1, in prostate cancer cell line LNCaP. Methods: After AR antagonist flutamide treatment and confirmation of its effect by phase contrast microscope and flow cytometry, the differential expression of the cell cycle-related genes was analyzed by a cDNA microarray. The flutamide treated cells were set as the experimental group and the LNCaP cells as the control. We labeled cDNA probes of the experimental group and control group with Cy5 and Cy3 dyes, respectively, through reverse transcription. Then we hybridized the cDNA probes with cDNA microarrays, which contained 8 126 unique human cDNA sequences and the chip was scanned to get the fluorescent values of Cy5 and Cy3 on each spot. After primary analysis, reverse transcription polymerase chain reaction (RTPCR) tests were carried out to confirm the results of the chips. Results:After AR antagonist flutamide treatment,three hundred and twenty-six genes (3.93 %) expressed differentially, 97 down-regulated and 219 up-regulated.Among them, eight up-regulated genes might be cell cycle-related, namely CDC10, NRAS, BTG1, Weel, CLK3,DKFZP564A122, CDKN1A and BTG2. The CDKN1A and BTG1 gene mRNA expression was confirmed to be higher in the experimental group by RT-PCR, whilep53 mRNA expression had no significant changes. Conclusion: Flutamide treatment might up-regulate CDKN1A and BTG1 expression in prostate cancer cells. The protein expressions of CDKN1A and BTG1 play an important role in inhibiting the proliferation of cancer cells. CDKN1A has a great impact on the cell cycle of prostate cancer cells and may play a role in the cancer cells in a p53-independent pathway. The prostate cancer cells might affect the cell cycle-related genes by activating AR and thus break the cell cycle control.

  3. Population structure and maturity stages of Fritillaria borealis (Appendicularia, Tunicata: seasonal cycle in Ushuaia Bay (Beagle Channel

    Directory of Open Access Journals (Sweden)

    María Laura Presta

    2015-09-01

    Full Text Available AbstractFritillaria borealis is a cosmopolitan species, very frequent in sub-antarctic and antarctic waters. The objective of this paper was to analyze its size structure and maturity stages at two sites in Ushuaia Bay: a coastal site exposed to anthropogenic pressure (E1 and a reference site (E2 located in the external zone of the bay. Zooplankton was collected during the 2012 seasonal cycle. The sampling method involved the use of a 67 µm-mesh net. Appendicularians were classified in four maturity stages: I undifferentiated gonads, II testis and ovary differentiated, III expanded testis, IV discharged testis, expanded ovary. Our results showed that the highest densities of F. borealisoccurred in spring and summer at both sites; coinciding with high values of chlorophyll-a. The percentage of juveniles (I and II exhibited a spatial and temporal pattern similar to that observed for chlorophyll-a values. During spring-summer, juveniles and mature specimens (III and IV showed a greater gonadal development than those individuals found in autumn-winter. In conclusion, the mismatching in the population structure and the pattern of densities of F. borealis between coastal and external zones would suggest the existence of two sub-populations susceptible to the influence of the anthropogenic impact in the bay.

  4. Cilium, centrosome and cell cycle regulation in polycystic kidney disease.

    Science.gov (United States)

    Lee, Kyung; Battini, Lorenzo; Gusella, G Luca

    2011-10-01

    Polycystic kidney disease is the defining condition of a group of common life-threatening genetic disorders characterized by the bilateral formation and progressive expansion of renal cysts that lead to end stage kidney disease. Although a large body of information has been acquired in the past years about the cellular functions that characterize the cystic cells, the mechanisms triggering the cystogenic conversion are just starting to emerge. Recent findings link defects in ciliary functions, planar cell polarity pathway, and centrosome integrity in early cystic development. Many of the signals dysregulated during cystogenesis may converge on the centrosome for its central function as a structural support for cilia formation and a coordinator of protein trafficking, polarity, and cell division. Here, we will discuss the contribution of proliferation, cilium and planar cell polarity to the cystic signal and will analyze in particular the possible role that the basal bodies/centrosome may play in the cystogenetic mechanisms. This article is part of a Special Issue entitled: Polycystic Kidney Disease. PMID:21376807

  5. Discovery of a Splicing Regulator Required for Cell Cycle Progression

    Energy Technology Data Exchange (ETDEWEB)

    Suvorova, Elena S.; Croken, Matthew; Kratzer, Stella; Ting, Li-Min; Conde de Felipe, Magnolia; Balu, Bharath; Markillie, Lye Meng; Weiss, Louis M.; Kim, Kami; White, Michael W.

    2013-02-01

    In the G1 phase of the cell division cycle, eukaryotic cells prepare many of the resources necessary for a new round of growth including renewal of the transcriptional and protein synthetic capacities and building the machinery for chromosome replication. The function of G1 has an early evolutionary origin and is preserved in single and multicellular organisms, although the regulatory mechanisms conducting G1 specific functions are only understood in a few model eukaryotes. Here we describe a new G1 mutant from an ancient family of apicomplexan protozoans. Toxoplasma gondii temperature-sensitive mutant 12-109C6 conditionally arrests in the G1 phase due to a single point mutation in a novel protein containing a single RNA-recognition-motif (TgRRM1). The resulting tyrosine to asparagine amino acid change in TgRRM1 causes severe temperature instability that generates an effective null phenotype for this protein when the mutant is shifted to the restrictive temperature. Orthologs of TgRRM1 are widely conserved in diverse eukaryote lineages, and the human counterpart (RBM42) can functionally replace the missing Toxoplasma factor. Transcriptome studies demonstrate that gene expression is downregulated in the mutant at the restrictive temperature due to a severe defect in splicing that affects both cell cycle and constitutively expressed mRNAs. The interaction of TgRRM1 with factors of the tri-SNP complex (U4/U6 & U5 snRNPs) indicate this factor may be required to assemble an active spliceosome. Thus, the TgRRM1 family of proteins is an unrecognized and evolutionarily conserved class of splicing regulators. This study demonstrates investigations into diverse unicellular eukaryotes, like the Apicomplexa, have the potential to yield new insights into important mechanisms conserved across modern eukaryotic kingdoms.

  6. Mechanisms involved in alternariol-induced cell cycle arrest

    International Nuclear Information System (INIS)

    Alternariol (AOH), a mycotoxin produced by Alternaria sp, is often found as a contaminant in fruit and cereal products. Here we employed the murine macrophage cell line RAW 264.7 to test the hypothesis that AOH causes toxicity as a response to DNA damage. AOH at concentrations of 15–30 μM almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 μM) significantly increased the level of reactive oxygen species (ROS). Furthermore, DNA base oxidations as well as DNA strand breaks and/or alkaline labile sites were detected by the comet assay after 2 h exposure of AOH. Cell death (mostly necrosis) was observed after prolonged exposure to the highest concentration of AOH (60 μM for 24 and 48 h) in our study. The DNA damage response involved phosphorylation (activation) of histone H2AX and check point kinase-1- and 2 (Chk-1/2). Moreover, AOH activated p53 and increased the expression of p21, Cyclin B, MDM2, and Sestrin 2; likewise the level of several miRNA was affected. AOH-induced Sestrin 2 expression was regulated by p53 and could at least partly be inhibited by antioxidants, suggesting a role of ROS in the response. Interestingly, the addition of antioxidants did not inhibit cell cycle arrest. Although the formation of ROS by itself was not directly linked cell proliferation, AOH-induced DNA damage and resulting transcriptional changes in p21, MDM2, and Cyclin B likely contribute to the reduced cell proliferation; while Sestrin 2 would contribute to the oxidant defense.

  7. Mechanisms involved in alternariol-induced cell cycle arrest

    Energy Technology Data Exchange (ETDEWEB)

    Solhaug, A., E-mail: Anita.Solhaug@vetinst.no [Norwegian Veterinary Institute, Oslo (Norway); Vines, L.L. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Ivanova, L.; Spilsberg, B. [Norwegian Veterinary Institute, Oslo (Norway); Holme, J.A. [Norwegian Institute of Public Health, Division of Environmental Medicine, Oslo (Norway); Pestka, J. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Collins, A. [University of Oslo, Department of Nutrition, Faculty of Medicine, Oslo (Norway); Eriksen, G.S. [Norwegian Veterinary Institute, Oslo (Norway)

    2012-10-15

    Alternariol (AOH), a mycotoxin produced by Alternaria sp, is often found as a contaminant in fruit and cereal products. Here we employed the murine macrophage cell line RAW 264.7 to test the hypothesis that AOH causes toxicity as a response to DNA damage. AOH at concentrations of 15-30 {mu}M almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 {mu}M) significantly increased the level of reactive oxygen species (ROS). Furthermore, DNA base oxidations as well as DNA strand breaks and/or alkaline labile sites were detected by the comet assay after 2 h exposure of AOH. Cell death (mostly necrosis) was observed after prolonged exposure to the highest concentration of AOH (60 {mu}M for 24 and 48 h) in our study. The DNA damage response involved phosphorylation (activation) of histone H2AX and check point kinase-1- and 2 (Chk-1/2). Moreover, AOH activated p53 and increased the expression of p21, Cyclin B, MDM2, and Sestrin 2; likewise the level of several miRNA was affected. AOH-induced Sestrin 2 expression was regulated by p53 and could at least partly be inhibited by antioxidants, suggesting a role of ROS in the response. Interestingly, the addition of antioxidants did not inhibit cell cycle arrest. Although the formation of ROS by itself was not directly linked cell proliferation, AOH-induced DNA damage and resulting transcriptional changes in p21, MDM2, and Cyclin B likely contribute to the reduced cell proliferation; while Sestrin 2 would contribute to the oxidant defense.

  8. The Yeast Cyclin-Dependent Kinase Routes Carbon Fluxes to Fuel Cell Cycle Progression.

    Science.gov (United States)

    Ewald, Jennifer C; Kuehne, Andreas; Zamboni, Nicola; Skotheim, Jan M

    2016-05-19

    Cell division entails a sequence of processes whose specific demands for biosynthetic precursors and energy place dynamic requirements on metabolism. However, little is known about how metabolic fluxes are coordinated with the cell division cycle. Here, we examine budding yeast to show that more than half of all measured metabolites change significantly through the cell division cycle. Cell cycle-dependent changes in central carbon metabolism are controlled by the cyclin-dependent kinase (Cdk1), a major cell cycle regulator, and the metabolic regulator protein kinase A. At the G1/S transition, Cdk1 phosphorylates and activates the enzyme Nth1, which funnels the storage carbohydrate trehalose into central carbon metabolism. Trehalose utilization fuels anabolic processes required to reliably complete cell division. Thus, the cell cycle entrains carbon metabolism to fuel biosynthesis. Because the oscillation of Cdk activity is a conserved feature of the eukaryotic cell cycle, we anticipate its frequent use in dynamically regulating metabolism for efficient proliferation. PMID:27203178

  9. RNA interference-mediated silencing of mitotic kinesin KIF14 disrupts cell cycle progression and induces cytokinesis failure.

    Science.gov (United States)

    Carleton, Michael; Mao, Mao; Biery, Matthew; Warrener, Paul; Kim, Sammy; Buser, Carolyn; Marshall, C Gary; Fernandes, Christine; Annis, James; Linsley, Peter S

    2006-05-01

    KIF14 is a microtubule motor protein whose elevated expression is associated with poor-prognosis breast cancer. Here we demonstrate KIF14 accumulation in mitotic cells, where it associated with developing spindle poles and spindle microtubules. Cells at later stages of mitosis were characterized by the concentration of KIF14 at the midbody. Time-lapse microscopy revealed that strong RNA interference (RNAi)-mediated silencing of KIF14 induced cytokinesis failure, causing several rounds of endoreduplication and resulting in multinucleated cells. Additionally, less efficacious KIF14-specific short interfering RNAs (siRNAs) induced multiple phenotypes, all of which resulted in acute apoptosis. Our data demonstrate the ability of siRNA-mediated silencing to generate epiallelic hypomorphs associated with KIF14 depletion. Furthermore, the link we observed between siRNA efficacy and phenotypic outcome indicates that distinct stages during cell cycle progression are disrupted by the differential modulation of KIF14 expression. PMID:16648480

  10. Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer

    Science.gov (United States)

    2016-02-08

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  11. Meiotic and Mitotic Cell Cycle Mutants Involved in Gametophyte Development in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Jingjing Liu; Li-Jia Qu

    2008-01-01

    The alternation between diploid and haploid generations is fundamentalin the life cycles of both animals and plants.The meiotic cell cycle is common to both animals and plants gamete formation, but in animals the products of meiosis are gametes,whereas for most plants,subsequent mitotic cell cycles are needed for their formation. Clarifying the regulatory mechanisms of mitotic cell cycle progression during gametophyte development will help understanding of sexual reproduction in plants.Many mutants defective in gametophyte development and,in particular,many meiotic and mitotic cell cycle mutants in Arabidopsis male and female gametophyte development were identified through both forward and reverse genetics approaches.

  12. Cell cycle-dependent DNA damage signaling induced by ICRF-193 involves ATM, ATR, CHK2, and BRCA1

    International Nuclear Information System (INIS)

    Topoisomerase II is essential for cell proliferation and survival and has been a target of various anticancer drugs. ICRF-193 has long been used as a catalytic inhibitor to study the function of topoisomerase II. Here, we show that ICRF-193 treatment induces DNA damage signaling. Treatment with ICRF-193 induced G2 arrest and DNA damage signaling involving γ-H2AX foci formation and CHK2 phosphorylation. DNA damage by ICRF-193 was further demonstrated by formation of the nuclear foci of 53BP1, NBS1, BRCA1, MDC1, and FANCD2 and increased comet tail moment. The DNA damage signaling induced by ICRF-193 was mediated by ATM and ATR and was restricted to cells in specific cell cycle stages such as S, G2, and mitosis including late and early G1 phases. Downstream signaling of ATM and ATR involved the phosphorylation of CHK2 and BRCA1. Altogether, our results demonstrate that ICRF-193 induces DNA damage signaling in a cell cycle-dependent manner and suggest that topoisomerase II might be essential for the progression of the cell cycle at several stages including DNA decondensation

  13. Selenium Inhibits Metastasis of Murine Melanoma Cells through the Induction of Cell Cycle Arrest and Cell Death

    OpenAIRE

    SONG, HYUNKEUN; Hur, Indo; Park, Hyun-jin; Nam, Joohyung; PARK, GA BIN; Kong, Kyoung Hye; Hwang, Young Mi; KIM, YEONG SEOK; Cho, Dae Ho; Lee, Wang Jae; Hur, Dae Young

    2009-01-01

    Background Melanoma is the most fatal form of skin cancer due to its rapid metastasis. Recently, several studies reported that selenium can induce apoptosis in melanoma cells. However, the precise mechanism remains to be elucidated. In this study, we investigated the effect of selenium on cell proliferation in murine melanoma and on tumor growth and metastasis in C57BL/6 mice. Methods Cell proliferation was measured by MTT assay in selenium-treated melanoma cells. Cell cycle distribution was ...

  14. Does MW Radiation Affect Gene Expression, Apoptotic Level, and Cell Cycle Progression of Human SH-SY5Y Neuroblastoma Cells?

    Science.gov (United States)

    Kayhan, Handan; Esmekaya, Meric Arda; Saglam, Atiye Seda Yar; Tuysuz, Mehmed Zahid; Canseven, Ayşe Gulnihal; Yagci, Abdullah Munci; Seyhan, Nesrin

    2016-06-01

    Neuroblastoma (NB) is a cancer that occurs in sympathetic nervous system arising from neuroblasts and nerve tissue of the adrenal gland, neck, chest, or spinal cord. It is an embryonal malignancy and affects infants and children. In this study, we investigated the effects of microwave (MW) radiation on apoptotic activity, cell viability, and cell cycle progression in human SH-SY5Y NB cells which can give information about MW radiation effects on neural cells covering the period from the embryonic stages to infants. SH-SY5Y NB cells were exposed to 2.1 GHz W-CDMA modulated MW radiation for 24 h at a specific absorption rate of 0.491 W/kg. Control samples were in the same conditions with MW-exposed samples but they were not exposed to MW radiation. The apoptotic activity of cells was measured by Annexin-V-FITC and propidium iodide staining. Moreover, mRNA levels of proliferative and cell cycle proteins were determined by real-time RT-PCR. The change in cell cycle progression was observed by using CycleTest-Plus DNA reagent. No significant change was observed in apoptotic activity of MW-exposed cells compared to control cells. The mRNA levels of c-myc and cyclin D1 were significantly reduced in MW group (p CDMA modulated MW radiation did not cause apoptotic cell death but changed cell cycle progression. PMID:27260669

  15. DUBbing Cancer: Deubiquitylating Enzymes Involved in Epigenetics, DNA Damage and the Cell Cycle As Therapeutic Targets

    Science.gov (United States)

    Pinto-Fernandez, Adan; Kessler, Benedikt M.

    2016-01-01

    Controlling cell proliferation is one of the hallmarks of cancer. A number of critical checkpoints ascertain progression through the different stages of the cell cycle, which can be aborted when perturbed, for instance by errors in DNA replication and repair. These molecular checkpoints are regulated by a number of proteins that need to be present at the right time and quantity. The ubiquitin system has emerged as a central player controlling the fate and function of such molecules such as cyclins, oncogenes and components of the DNA repair machinery. In particular, proteases that cleave ubiquitin chains, referred to as deubiquitylating enzymes (DUBs), have attracted recent attention due to their accessibility to modulation by small molecules. In this review, we describe recent evidence of the critical role of DUBs in aspects of cell cycle checkpoint control, associated DNA repair mechanisms and regulation of transcription, representing pathways altered in cancer. Therefore, DUBs involved in these processes emerge as potentially critical targets for the treatment of not only hematological, but potentially also solid tumors.

  16. Socioeconomic position and surgery for early-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Starr, Laila Kærgaard; Osler, Merete; Steding-Jessen, Marianne;

    2012-01-01

    explain the association with income or living alone for early-stage NSCLC patients. CONCLUSION: Early-stage NSCLC patients with low income or who live alone are less likely to undergo surgery than those with a high income or who live with a partner, even after control for possible explanatory factors......AIM: To examine possible associations between socioeconomic position and surgical treatment of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: In a register-based clinical cohort study, patients with early-stage (stages I-IIIa) NSCLC were identified in the Danish Lung Cancer...... and separately for stages I, II and IIIa. RESULTS: Of the 5538 eligible patients with stages I-IIIa NSCLC diagnosed 2001-2008, 53% underwent surgery. Higher stage, older age, being female and diagnosis early in the study period were associated with higher odds for not receiving surgery. Low disposable...

  17. Peripheral blood stem cell harvest in patients with limited stage small-cell lung cancer

    International Nuclear Information System (INIS)

    Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood stem cells (PBSC) was performed in patients with limited stage small-cell lung cancer. Chemotherapy consisted of cisplatin/etoposide or cisplatin/adriamycin/etoposide. The amounts of CD34 positive cells and granulocyte-macrophage colony forming units (CFU-GM) collected during 2-3 courses of apheresis were 3.1±2.9 x 106/kg (n=10) and 3.1±1.5 x 105/kg (n=8) , respectively. Adequate amounts of PBSC were also harvested even in patients treated with concurrent chemoradiotherapy. Eight patients were successfully treated with high-dose chemotherapy consisting of ifosfamide, carboplatin and etoposide with PBSC transfusion. The patients'-bone marrow reconstruction was rapid and no treatment-related death was observed. (author)

  18. Identification of Cell Cycle-regulated Genes in Fission YeastD⃞

    OpenAIRE

    Peng, Xu; Karuturi, R Krishna Murthy; Miller, Lance D.; Lin, Kui; Jia, Yonghui; Kondu, Pinar; Wang, Long; Wong, Lim-Soon; Liu, Edison T.; Balasubramanian, Mohan K.; Liu, Jianhua

    2005-01-01

    Cell cycle progression is both regulated and accompanied by periodic changes in the expression levels of a large number of genes. To investigate cell cycle-regulated transcriptional programs in the fission yeast Schizosaccharomyces pombe, we developed a whole-genome oligonucleotide-based DNA microarray. Microarray analysis of both wild-type and cdc25 mutant cell cultures was performed to identify transcripts whose levels oscillated during the cell cycle. Using an unsupervised algorithm, we id...

  19. Propionibacterium acnes inhibits FOXM1 and induces cell cycle alterations in human primary prostate cells

    DEFF Research Database (Denmark)

    Sayanjali, Behnam; Christensen, Gitte J M; Al-Zeer, Munir A;

    2016-01-01

    Propionibacterium acnes has been detected in diseased human prostate tissue, and cell culture experiments suggest that the bacterium can establish a low-grade inflammation. Here, we investigated its impact on human primary prostate epithelial cells. Microarray analysis confirmed the inflammation......-inducing capability of P. acnes but also showed deregulation of genes involved in the cell cycle. qPCR experiments showed that viable P. acnes downregulates a master regulator of cell cycle progression, FOXM1. Flow cytometry experiments revealed that P. acnes increases the number of cells in S-phase. We tested the...... hypothesis that a P. acnes-produced berninamycin-like thiopeptide is responsible for this effect, since it is related to the FOXM1 inhibitor siomycin. The thiopeptide biosynthesis gene cluster was strongly expressed; it is present in subtype IB of P. acnes, but absent from type IA, which is most abundant on...

  20. Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro

    International Nuclear Information System (INIS)

    Glioma stem cells in the quiescent state are resistant to clinical radiation therapy. An almost inevitable glioma recurrence is due to the persistence of these cells. The high linear energy transfer associated with boron neutron capture therapy (BNCT) could kill quiescent and proliferative cells. The present study aimed to evaluate the effects of BNCT on glioma stem/progenitor cells in vitro. The damage induced by BNCT was assessed using cell cycle progression, apoptotic cell ratio and apoptosis-associated proteins expression. The surviving fraction and cell viability of glioma stem/progenitor cells were decreased compared with differentiated glioma cells using the same boronophenylalanine pretreatment and the same dose of neutron flux. BNCT induced cell cycle arrest in the G2/M phase and cell apoptosis via the mitochondrial pathway, with changes in the expression of associated proteins. Glioma stem/progenitor cells, which are resistant to current clinical radiotherapy, could be effectively killed by BNCT in vitro via cell cycle arrest and apoptosis using a prolonged neutron irradiation, although radiosensitivity of glioma stem/progenitor cells was decreased compared with differentiated glioma cells when using the same dose of thermal neutron exposure and boronophenylalanine pretreatment. Thus, BNCT could offer an appreciable therapeutic advantage to prevent tumor recurrence, and may become a promising treatment in recurrent glioma

  1. Effects of HIV-1 Tat protein on expression of cell cycle-related genes and radiation-induced cell cycle arrest

    International Nuclear Information System (INIS)

    Objective: To explore effects of HIV-1 Tat protein on the expression of cell cycle-related genes and cell cycle arrest induced by ionizing radiation. Methods: A human rhabdomyosarcoma cell line TE671 and TT2 cells generated from TE671 cells by transfecting with tat gene of the HIV-1 strain were employed. Microarray, which contained the oligonucleotide probes corresponding to 102 human DNA damage response related genes, was used to analyze transcriptional changes. Cell cycle changes were analyzed by flow cytometry. Results: Microarray assay demonstrated that cell cycle-related genes Cdc20, Cdc25C, KIF2C, CTS1 and Wee1 were down-regulated in Tat-expressing TT2 cells. Tat-expressing cells exhibited a noticeable delay of the initiation and elimination of radiation-induced G2/M arrest and a prolonged S phase arrest as compared with parental cells. Moreover, overexpression of cyclinB1 was also observed in Tat-expressing TT2 cells. Conclusion: Dysregulated cell cycle checkpoint in Tat-expressing cells can provide new information for understanding the radiation responsiveness of AIDS patients with cancer to radiotherapy. (authors)

  2. A NGS approach to the encrusting Mediterranean sponge Crella elegans (Porifera, Demospongiae, Poecilosclerida): transcriptome sequencing, characterization and overview of the gene expression along three life cycle stages.

    Science.gov (United States)

    Pérez-Porro, A R; Navarro-Gómez, D; Uriz, M J; Giribet, G

    2013-05-01

    Sponges can be dominant organisms in many marine and freshwater habitats where they play essential ecological roles. They also represent a key group to address important questions in early metazoan evolution. Recent approaches for improving knowledge on sponge biological and ecological functions as well as on animal evolution have focused on the genetic toolkits involved in ecological responses to environmental changes (biotic and abiotic), development and reproduction. These approaches are possible thanks to newly available, massive sequencing technologies-such as the Illumina platform, which facilitate genome and transcriptome sequencing in a cost-effective manner. Here we present the first NGS (next-generation sequencing) approach to understanding the life cycle of an encrusting marine sponge. For this we sequenced libraries of three different life cycle stages of the Mediterranean sponge Crella elegans and generated de novo transcriptome assemblies. Three assemblies were based on sponge tissue of a particular life cycle stage, including non-reproductive tissue, tissue with sperm cysts and tissue with larvae. The fourth assembly pooled the data from all three stages. By aggregating data from all the different life cycle stages we obtained a higher total number of contigs, contigs with blast hit and annotated contigs than from one stage-based assemblies. In that multi-stage assembly we obtained a larger number of the developmental regulatory genes known for metazoans than in any other assembly. We also advance the differential expression of selected genes in the three life cycle stages to explore the potential of RNA-seq for improving knowledge on functional processes along the sponge life cycle. PMID:23437888

  3. Formula G1: Cell cycle in the driver's seat of stem cell fate determination.

    Science.gov (United States)

    Julian, Lisa M; Carpenedo, Richard L; Rothberg, Janet L Manias; Stanford, William L

    2016-04-01

    Cell cycle dynamics has emerged as a key regulator of stem cell fate decisions. In particular, differentiation decisions are associated with the G1 phase, and recent evidence suggests that self-renewal is actively regulated outside of G1. The mechanisms underlying these phenomena are largely unknown, but direct control of gene regulatory programs by the cell cycle machinery is heavily implicated. A recent study sheds important mechanistic insight by demonstrating that in human embryonic stem cells (hESCs) the Cyclin-dependent kinase CDK2 controls a wide-spread epigenetic program that drives transcription at differentiation-related gene promoters specifically in G1. Here, we discuss this finding and explore whether similar mechanisms are likely to function in multipotent stem cells. The implications of this discovery toward our understanding of stem cell-related disease are discussed, and we postulate novel mechanisms that position the cell cycle as a regulator of cell fate gene networks at epigenetic, transcriptional and post-transcriptional levels. PMID:26857166

  4. Involvement of apoptotic cell death and cell cycle perturbation in retinoic acid-induced cleft palate in mice

    International Nuclear Information System (INIS)

    Retinoic acid (RA), a metabolite of vitamin A, plays a key role in a variety of biological processes and is essential for normal embryonic development. On the other hand, exogenous RA could cause cleft palate in offspring when it is given to pregnant animals at either the early or late phases of palatogenesis, but the pathogenetic mechanism of cleft palate caused by excess RA remains not fully elucidated. The aim of the present study was to investigate the effects of excess of RA on early palatogenesis in mouse fetuses and analyze the teratogenic mechanism, especially at the stage prior to palatal shelf elevation. We gave all-trans RA (100 mg/kg) orally to E11.5 ICR pregnant mice and observed the changes occurring in the palatal shelves of their fetuses. It was found that apoptotic cell death increased not only in the epithelium of the palatal shelves but also in the tongue primordium, which might affect tongue withdrawal movement during palatogenesis and impair the horizontal elevation of palatal shelves. In addition, RA was found to prevent the G1/S progression of palatal mesenchymal cells through upregulation of p21 Cip1, leading to Rb hypophospholylation. Thus, RA appears to cause G1 arrest in palatal mesenchymal cells in a similar manner as in various cancer and embryonic cells. It is likely that apoptotic cell death and cell cycle disruption are involved in cleft palate formation induced by RA

  5. Exosomes Secreted by Toxoplasma gondii-Infected L6 Cells: Their Effects on Host Cell Proliferation and Cell Cycle Changes

    OpenAIRE

    Kim, Min Jae; Jung, Bong-Kwang; Cho, Jaeeun; Song, Hyemi; Pyo, Kyung-Ho; Lee, Ji Min; Kim, Min-Kyung; Chai, Jong-Yil

    2016-01-01

    Toxoplasma gondii infection induces alteration of the host cell cycle and cell proliferation. These changes are not only seen in directly invaded host cells but also in neighboring cells. We tried to identify whether this alteration can be mediated by exosomes secreted by T. gondii-infected host cells. L6 cells, a rat myoblast cell line, and RH strain of T. gondii were selected for this study. L6 cells were infected with or without T. gondii to isolate exosomes. The cellular growth patterns w...

  6. Combination Chemotherapy and Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Peripheral T-cell Non-Hodgkin's Lymphoma

    Science.gov (United States)

    2015-10-02

    Anaplastic Large Cell Lymphoma, ALK-Negative; Anaplastic Large Cell Lymphoma, ALK-Positive; Hepatosplenic T-Cell Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Stage II Angioimmunoblastic T-cell Lymphoma; Stage II Enteropathy-Associated T-Cell Lymphoma; Stage III Angioimmunoblastic T-cell Lymphoma; Stage III Enteropathy-Associated T-Cell Lymphoma; Stage IV Angioimmunoblastic T-cell Lymphoma; Stage IV Enteropathy-Associated T-Cell Lymphoma

  7. Biotin Uptake into Human Peripheral Blood Mononuclear Cells Increases Early in the Cell Cycle, Increasing Carboxylase Activities1,2

    OpenAIRE

    Stanley, J. Steven; Mock, Donald M.; Griffin, Jacob B.; Zempleni, Janos

    2002-01-01

    Cells respond to proliferation with increased accumulation of biotin, suggesting that proliferation enhances biotin demand. Here we determined whether peripheral blood mononuclear cells (PBMC) increase biotin uptake at specific phases of the cell cycle, and whether biotin is utilized to increase biotinylation of carboxylases. Biotin uptake was quantified in human PBMC that were arrested chemically at specific phases of the cell cycle, i.e., biotin uptake increased in the G1 phase of the cycle...

  8. Cell-mediated immunity elicited by the blood stage malaria vaccine apical membrane antigen 1 in Malian adults: Results of a Phase I randomized trial

    OpenAIRE

    Lyke, Kirsten E; Daou, Modibo; DIARRA, ISSA; Kone, Abdoulaye; Kouriba, Bourema; Thera, Mohamadou A.; Dutta, Sheetij; Lanar, David E.; Heppner, D Gray; Doumbo, Ogobara K.; Plowe, Christopher V.; Sztein, Marcelo B.

    2009-01-01

    The development of a safe and effective malaria vaccine is impeded by the complexity of the Plasmodium life cycle. A vaccine that elicits both cell-mediated and humoral immune responses might be needed for protection against this multistage parasitic infection. Apical membrane antigen 1 (AMA-1) plays a key role in erythrocytic invasion but is also expressed in sporozoites and in late stage liver schizonts, where it may provide a target of protective cell-mediated immunity (CMI). A Phase 1 tri...

  9. Business cycles and the financial performance of fuel cell companies

    International Nuclear Information System (INIS)

    Fuel cells are expected to play a major role in a hydrogen powered world. They will provide power to homes, modes of transportation and appliances. Hydrogen is the most abundant element in nature, but it must be extracted in order to be usable. It can be produced from oil, natural gas and coal or from renewable sources such as biomass, thermal or nuclear reactions. Fuel cells running on hydrogen extracted from non renewable resources have an efficiency of 30 per cent, which is twice as efficient as an internal combustion engine. The greatest barrier to mass commercialization is the cost of making hydrogen-powered auto engines. Also, an infrastructure must be developed to refill hydrogen cars. One solution is to build a hydrogen highway using the existing natural gas grid to produce hydrogen and sell it at existing filling stations. The cost of building 12,000 refueling pumps in urban areas which will provide access to 70 per cent of America's population is estimated at $10 to $15 billion. This paper described the vector autoregression (VAR) model which empirically examines the relationship between financial performance of fuel cell companies and business cycles. It was used to measure how sensitive the financial performance of fuel cell companies are to changes in macroeconomic activity. A four variable VAR model was developed to examine the relationship between stock prices, oil prices and interest rates. It was shown that the stock prices of fuel cell companies are affected by shocks to technology stock prices and oil prices, with the former having a longer lasting impact. These results add to the growing literature that oil price movements are not as important as once thought. 15 refs., 3 tabs., 3 figs

  10. Regulation of histone gene expression during the cell cycle.

    Science.gov (United States)

    Meshi, T; Taoka, K I; Iwabuchi, M

    2000-08-01

    The steady-state level of histone mRNAs fluctuates coordinately with chromosomal DNA synthesis during the cell cycle. Such an S phase-specific expression pattern results from transcriptional activation of histone genes coupled with the onset of replication and from transcriptional repression of the genes as well as specific destabilization of histone mRNAs around the end of the S phase. Proliferation-coupled and S phase-specific expression of histone genes is primarily achieved by the activities of the proximal promoter regions, where several conserved cis-acting elements have been identified. Among them, three kinds of Oct-containing composite elements (OCEs) play a pivotal role in S phase-specific transcriptional activation. Other ones, such as Nona, solo-Oct, and CCGTC motifs, appear to modulate the functions of OCEs to enhance or repress the transcriptional level, possibly depending on the state of the cells. Here, we review the growing evidence concerning the regulatory mechanisms by which plant histone genes are expressed S phase-specifically in proliferating cells. PMID:11089867

  11. Effect of cell cycle inhibitor p19ARF on senescence of human diploid cell

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To investigate the effect of cell cycle inhibitor p19ARF on replicative senescence of human diploid cell, recombinant p19ARF eukaryotic expression vector was constructed and p19ARF gene was transfected into human diploid fibroblasts (WI-38 cells) by liposome-mediated transfection for overexpression. Then, the effects of p19ARF on replicative senescence of WI-38 cells were observed. The results re- vealed that, compared with control cells, the WI-38 cells in which p19ARF gene was introduced showed significant up-regulation of p53 and p21 expression level, decrease of cell generation by 10 12 generations, decline of cell growth rate with cell cycle being arrested at G1 phase, increase of positive rate of senescent marker SA-β-gal staining, and decrease of mitochondrial membrane potential. The morphology of the transfected fibroblasts presented the characteristics changes similar to senescent cells. These results indicated that high expression of p19ARF may promote the senescent process of human diploid cells.

  12. Twice daily radiation therapy plus concurrent chemotherapy for limited-stage small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yeo, Seung Gu; Cho, Moon June; Kim, Sun Young; Kim, Ki Whan; Kim, Jun Sang [Chungnam National University Hospital, Daejeon (Korea, Republic of)

    2006-06-15

    A retrospective study was performed to evaluate the efficiency and feasibility of twice daily radiation therapy plus concurrent chemotherapy for limited-stage small cell lung cancer in terms of treatment response, survival, patterns of failure, and acute toxicities. Between February 1993 and October 2002, 76 patients of histologically proven limited-stage small cell lung cancer (LS-SCLC) were treated with twice daily radiation therapy and concurrent chemotherapy. Male was in 84% (64/76), and median age was 57 years (range, 32 {approx} 75 years). Thoracic radiation therapy consisted of 120 or 150 cGy per fraction, twice a day at least 6 hours apart, 5 days a week. Median total dose was 50.4 Gy (range, 45 {approx} 51 Gy). Concurrent chemotherapy consisted of CAV (cytoxan 1000 mg/m{sup 2}, adriamycin 40 mg/m{sup 2}, vincristine 1 mg/m{sup 2}) alternating with PE (cisplatin 60 mg/m{sup 2}, etoposide 100 mg/m{sup 2}) or PE alone, every 3 weeks. The median cycle of chemotherapy was six (range, 1 {approx} 9 cycle). Prophylactic cranial irradiation (PCI) was recommended to the patients who achieved a complete response (CR). PCI scheme was 25 Gy/ 10 fractions. Median follow up was 18 months (range, 1 {approx} 136 months). Overall response rate was 86%; complete response in 39 (52%) and partial response in 26 (34%) patients. The median overall survival was 23 months. One, two, and three year overall survival rate was 72%, 50% and 30%, respectively. In univariate analysis, the treatment response was revealed as a significant favorable prognostic factor for survival ({rho} < 0.001). Grade 3 or worse acute toxicities were leukopenia in 46 (61%), anemia in 5 (6%), thrombocytopenia in 10 (13%), esophagitis in 5 (6%), and pulmonary toxicity in 2 (2%) patients. Of 73 evaluable patients, 40 (55%) patients subsequently had disease progression. The most frequent first site of distant metastasis was brain. Twice daily radiation therapy plus concurrent chemotherapy produced favorable

  13. Role of Ran GTPase in cell cycle regulation

    Institute of Scientific and Technical Information of China (English)

    JIANG Qing; LU Zhigang; ZHANG Chuanmao

    2004-01-01

    Ran, a member of the Ras GTPase superfamily,is a multifunctional protein and abundant in the nucleus.Many evidences suggest that Ran and its interacting proteins are involved in multiple aspects of the cell cycle regulation.So far it has been conformed that Ran and its interacting proteins control the nucleocytoplasmic transport, the nuclear envelope (NE) assembly, the DNA replication and the spindle assembly, although many details of the mechanisms are waiting for elucidation. It has also been implicated that Ran and its interacting proteins are involved in regulating the integrity of the nuclear structure, the mRNA transcription and splicing, and the RNA transport from the nucleus to the cytoplasm. In this review we mainly discuss the mechanisms by which Ran and its interacting proteins regulate NE assembly, DNA replication and spindle assembly.

  14. Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma

    Directory of Open Access Journals (Sweden)

    Telang Sucheta

    2011-12-01

    Full Text Available Abstract Background We previously found that administration of an interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; ONTAK to stage IV melanoma patients depleted CD4+CD25HIFoxp3+ regulatory T cells and expanded melanoma-specific CD8+ T cells. The goal of this study was to assess the clinical efficacy of DAB/IL2 in an expanded cohort of stage IV melanoma patients. Methods In a single-center, phase II trial, DAB/IL2 (12 μg/kg; 4 daily doses; 21 day cycles was administered to 60 unresectable stage IV melanoma patients and response rates were assessed using a combination of 2-[18 F]-fluoro-2-deoxy-glucose (FDG-positron emission tomography (PET and computed tomography (CT imaging. Results After DAB/IL2 administration, 16.7% of the 60 patients had partial responses, 5% stable disease and 15% mixed responses. Importantly, 45.5% of the chemo/immuno-naïve sub-population (11/60 patients experienced partial responses. One year survival was markedly higher in partial responders (80 ± 11.9% relative to patients with progressive disease (23.7 ± 6.5%; p value Conclusions These data support the development of multi-center, randomized trials of DAB/IL2 as a monotherapy and in combination with other immunotherapeutic agents for the treatment of stage IV melanoma. Trial registration NCT00299689

  15. Effect of polo-like kinase 1 gene silence on cell cycle and drug resistance in K562/A02 cell

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Polo-like kinase 1(PLK1) plays an important role in many cell-cycle-related events.1 At G2/M transition, PLK1 contributes to the activation of cyclinB/Cdc by phosphorylation of Cdc25C, centrosome functional maturation, bipolar spindle formation. In later stage of mitosis, PLK1 is involved in regulating components of the anaphase-promoting complex (APC) for mitotic exit and in the execution of cytokinesis.

  16. Progress and challenge in the treatment of end-stage liver disease with stem cells

    Directory of Open Access Journals (Sweden)

    Ming SHI

    2013-09-01

    Full Text Available Stem cells, including embryonic stem cells and adult stem cells, are multipotent cells that have self-renewing abilities and the potential to differentiate into various types of cells, and to repair various tissue damages. Bone marrow is the major source of adult stem cells, including mainly the bone marrow hematopoietic stem cells and mesenchymal stem cells. End-stage liver disease is a serious clinical systemic syndrome, and the use of stem cells in the treatment of end-stage liver disease has received more and more attention. This review summarizes the research progresses of stem cells, especially adult stem cells, in respect of the treatment of end-stage liver disease in the form of in vitro study, animal experimentation and clinical research, with emphasis on the research progress in the use of stem cells of various sources in clinical application, discussion of possible mechanisms of stem cell therapy for end-stage liver disease, to point out the problems existing in current research, and to look forward to the prospect of future application.

  17. Effect of genistein on cell cycle of bone marrow hematopoietic cells in normal and irradiated mice

    International Nuclear Information System (INIS)

    Objective: To study the effects of genistein on cell cycle, proliferation and expression of bcl-2 gene in bone marrow hematopoietic cells (BMHCs) of normal and irradiated mice in order to explore mechanisms for protection of genistein from radiation-induced hematopoietic system injury. Methods: Adult male BALB/c mice were orally administered with genistein (160 mg/kg b.w.) 24 h before irradiation. Cell cycles in BMHCs of the normal and irradiated mice were measured by flow cytometry. The protein and mRNA expressions of bcl-2 gene in BMHCs were analyzed by Western blot and RT-PCR, respectively. Results: a) Transitory and significant changes occurred in the cell cycle of BMHCs in the normal mice after administration of genistein: first, the proliferation suppression of BMHCs was observed and most cells were arrested in G0/G1 phase on day 1; second, progression of cells from G0/G1 phase into S phase was observed, accumulation of cells in S phase on day 2, and back to the normal level on day 4. b) Genistein, administration 24 h before irradiation, decreased the percentage of BMHCs in G0/G1 phase and increased cell proliferation. Moreover, genistein up-regulated the protein and mRNA expressions of bcl-2 in BMHCs in the irradiated mice. Conclusions: It was shown that changing with cell cycle, strengthening of radioresistant, suppressing of radiation-induced apoptosis, and enhancing of proliferation and differentiation of BMHCs maybe the underlying mechanisms for genistein protection of hematopoietic system against radiation damage. (authors)

  18. Cell cycle arrest and cell survival induce reverse trends of cardiolipin remodeling.

    Directory of Open Access Journals (Sweden)

    Yu-Jen Chao

    Full Text Available Cell survival from the arrested state can be a cause of the cancer recurrence. Transition from the arrest state to the growth state is highly regulated by mitochondrial activity, which is related to the lipid compositions of the mitochondrial membrane. Cardiolipin is a critical phospholipid for the mitochondrial integrity and functions. We examined the changes of cardiolipin species by LC-MS in the transition between cell cycle arrest and cell reviving in HT1080 fibrosarcoma cells. We have identified 41 cardiolipin species by MS/MS and semi-quantitated them to analyze the detailed changes of cardiolipin species. The mass spectra of cardiolipin with the same carbon number form an envelope, and the C64, C66, C68, C70 C72 and C74 envelopes in HT1080 cells show a normal distribution in the full scan mass spectrum. The cardiolipin quantity in a cell decreases while entering the cell cycle arrest, but maintains at a similar level through cell survival. While cells awakening from the arrested state and preparing itself for replication, the groups with short acyl chains, such as C64, C66 and C68 show a decrease of cardiolipin percentage, but the groups with long acyl chains, such as C70 and C72 display an increase of cardiolipin percentage. Interestingly, the trends of the cardiolipin species changes during the arresting state are completely opposite to cell growing state. Our results indicate that the cardiolipin species shift from the short chain to long chain cardiolipin during the transition from cell cycle arrest to cell progression.

  19. Effect of p27KIP1 on cell cycle and apoptosis in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Jian-Yong Zheng; Wei-Zhong Wang; Kai-Zong Li; Wen-Xian Guan; Wei Yan

    2005-01-01

    AIM: To elucidate the effect of p27KIP1 on cell cycle and apoptosis regulation in gastric carcinoma cells.METHODS: The whole length of p27KIP1 cDNA was transfected into human gastric cancer cell line SCG7901by lipofectamine. Expression of p27KIP1 protein or mRNA was analyzed by Western blot and RNA dot blotting,respectively. Effect of p27KIP1 on cell growth was observed by MTT assay and anchorage-independent growth in soft agar. Tumorigenicity in nude mice was used to assess the in vivo biological effect of p27KIP1. Flow cytometry,TUNEL, and electron microscopy were used to assess the effect of p27KIP1 on cell cycle and apoptosis.RESULTS: Expression of p27KIP1 protein or mRNA increased evidently in SCG7901 cells transfected with p27KIP1. The cell growth was reduced by 31% at 48 h after induction with zinc determined by cell viability assay. The alteration of cell malignant phenotype was evidently indicated by the loss of anchorage-independent growth ability in soft agar. The tumorigenicity in nude mice was reduced evidently (0.55±0.14 cm vs 1.36±0.13crn, P<0.01). p27KIP1 overexpression caused cell arrest with 36% increase (from 33.7% to 69.3%,P<0.01) in G1 population. Prolonged p27KIP1 expression induced apoptotic cell death reflected by pre-G1 peak in the histogram of FACS, which was also confirmed by TUNEL assay and electron microscopy.CONCLUSION: p27KIP1 can prolong cell cycle in G1phase and lead to apoptosis. p27KIP1 may be a good candidate for cancer gene therapy.

  20. The Trypanosoma cruzi nucleic acid binding protein Tc38 presents changes in the intramitochondrial distribution during the cell cycle

    Directory of Open Access Journals (Sweden)

    Nardelli Sheila C

    2009-02-01

    Full Text Available Abstract Background Tc38 of Trypanosoma cruzi has been isolated as a single stranded DNA binding protein with high specificity for the poly [dT-dG] sequence. It is present only in Kinetoplastidae protozoa and its sequence lacks homology to known functional domains. Tc38 orthologues present in Trypanosoma brucei and Leishmania were proposed to participate in quite different cellular processes. To further understand the function of this protein in Trypanosoma cruzi, we examined its in vitro binding to biologically relevant [dT-dG] enriched sequences, its expression and subcellular localization during the cell cycle and through the parasite life stages. Results By using specific antibodies, we found that Tc38 protein from epimastigote extracts participates in complexes with the poly [dT-dG] probe as well as with the universal minicircle sequence (UMS, a related repeated sequence found in maxicircle DNA, and the telomeric repeat. However, we found that Tc38 predominantly localizes into the mitochondrion. Though Tc38 is constitutively expressed through non-replicating and replicating life stages of T. cruzi, its subcellular localization in the unique parasite mitochondrion changes according to the cell cycle stage. In epimastigotes, Tc38 is found only in association with kDNA in G1 phase. From the S to G2 phase the protein localizes in two defined and connected spots flanking the kDNA. These spots disappear in late G2 turning into a diffuse dotted signal which extends beyond the kinetoplast. This later pattern is more evident in mitosis and cytokinesis. Finally, late in cytokinesis Tc38 reacquires its association with the kinetoplast. In non-replicating parasite stages such as trypomastigotes, the protein is found only surrounding the entire kinetoplast structure. Conclusions The dynamics of Tc38 subcellular localization observed during the cell cycle and life stages support a major role for Tc38 related to kDNA replication and maintenance.

  1. Chromatin dynamics during cell cycle mediate conversion of DNA damage into chromatid breaks and affect formation of chromosomal aberrations: Biological and clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    Terzoudi, Georgia I.; Hatzi, Vasiliki I. [Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research ' Demokritos' , 15310 Ag. Paraskevi Attikis, Athens (Greece); Donta-Bakoyianni, Catherine [Oral Diagnosis and Radiology, University of Athens Dental School, Athens (Greece); Pantelias, Gabriel E., E-mail: gabriel@ipta.demokritos.gr [Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research ' Demokritos' , 15310 Ag. Paraskevi Attikis, Athens (Greece)

    2011-06-03

    The formation of diverse chromosomal aberrations following irradiation and the variability in radiosensitivity at different cell-cycle stages remain a long standing controversy, probably because most of the studies have focused on elucidating the enzymatic mechanisms involved using simple DNA substrates. Yet, recognition, processing and repair of DNA damage occur within the nucleoprotein complex of chromatin which is dynamic in nature, capable of rapid unfolding, disassembling, assembling and refolding. The present work reviews experimental work designed to investigate the impact of chromatin dynamics and chromosome conformation changes during cell-cycle in the formation of chromosomal aberrations. Using conventional cytogenetics and premature chromosome condensation to visualize interphase chromatin, the data presented support the hypothesis that chromatin dynamic changes during cell-cycle are important determinants in the conversion of sub-microscopic DNA lesions into chromatid breaks. Consequently, the type and yield of radiation-induced chromosomal aberrations at a given cell-cycle-stage depends on the combined effect of DNA repair processes and chromatin dynamics, which is cell-cycle-regulated and subject to up- or down-regulation following radiation exposure or genetic alterations. This new hypothesis is used to explain the variability in radiosensitivity observed at various cell-cycle-stages, among mutant cells and cells of different origin, or among different individuals, and to revisit unresolved issues and unanswered questions. In addition, it is used to better understand hypersensitivity of AT cells and to provide an improved predictive G2-assay for evaluating radiosensitivity at individual level. Finally, experimental data at single cell level obtained using hybrid cells suggest that the proposed hypothesis applies only to the irradiated component of the hybrid.

  2. Effects of tachyplesin on the regulation of cell cycle in human hepatocarcinoma SMMC-7721 cells

    Institute of Scientific and Technical Information of China (English)

    Qi-Fu Li; Gao-Liang Ouyang; Xuan-Xian Peng; Shui-Gen Hong

    2003-01-01

    AIM: To investigate the effects of tachyplesin on the cell cycle regulation in human hepatcarcinoma cells.METHODS: Effects of tachyplesin on the cell cycle in human hepatocarcinoma SMMC-7721 cells were assayed with flow cytometry. The protein levels of p53, p16, cyclin D1 and CDK4 were assayed by immunocytochemistry. The mRNA levels of p21WAF1/CIP1 and c-myc genes were examined with in situ hybridization assay.RESULTS: After tachyplesin treatment, the cell cycle arrested at G0/G1 phase, the protein levels of mutant p53, cyclin D1 and CDK4 and the mRNA level of c-myc gene were decreased, whereas the levels of p16 protein and p21wWF1/CIP1 mRNA increased.CONCLUSION: Tachyplesin might arrest the cell at G0/G1 phase by upregulating the levels of p16 protein and p21WAF1/CIP1 mRNA and downregulating the levels of mutant p53, cyclin D1 and CDK4 proteins and c-myc mRNA, and induce the differentiation of human hepatocacinoma cells.

  3. Effect of Juglone in qinglongyi on cell cycle status and apoptosis in A-549 cells

    Institute of Scientific and Technical Information of China (English)

    ZOU Xiang; KONG Ling-sheng; JI Yu-bin

    2008-01-01

    Objective To explore the inhibition of juglone in Qinglongyi on A-549 cells in vitro. Methods MTT assay was used. Laser confocal scanning microscope was used to observe apoptotic morphology.Changes of cell cycle are studied by flow cytometry analysis. Results MTT assay showed that juglone had a marked growth inhibition in A-549 cells and the IC50 is respectively 3.4×10-5 mol·L-1, 1.8×10-5 mol·L-1 and 2.6×10-6 mol·L-1 after treatment for 24, 48 and 72 h by juglone. Through Laser confocal scanning microscope, we can see that juglone can induce the apoptosis. Cell cycle changes are analyzed by flow cytometry with cells at G1 phase significantly less than those of control and ceils at G2 phase significantly more than those of control. Conclusions It suggests that juglone could apoptosis of A-549 cells with the cell cycle arrest on G2 phase in distinct dose-dependent manner.

  4. Quantitative proteomic analysis of cell cycle of the dinoflagellate Prorocentrum donghaiense (Dinophyceae.

    Directory of Open Access Journals (Sweden)

    Da-Zhi Wang

    Full Text Available Dinoflagellates are the major causative agents of harmful algal blooms in the coastal zone, which has resulted in adverse effects on the marine ecosystem and public health, and has become a global concern. Knowledge of cell cycle regulation in proliferating cells is essential for understanding bloom dynamics, and so this study compared the protein profiles of Prorocentrum donghaiense at different cell cycle phases and identified differentially expressed proteins using 2-D fluorescence difference gel electrophoresis combined with MALDI-TOF-TOF mass spectrometry. The results showed that the synchronized cells of P. donghaiense completed a cell cycle within 24 hours and cell division was phased with the diurnal cycle. Comparison of the protein profiles at four cell cycle phases (G1, S, early and late G2/M showed that 53 protein spots altered significantly in abundance. Among them, 41 were identified to be involved in a variety of biological processes, e.g. cell cycle and division, RNA metabolism, protein and amino acid metabolism, energy and carbon metabolism, oxidation-reduction processes, and ABC transport. The periodic expression of these proteins was critical to maintain the proper order and function of the cell cycle. This study, to our knowledge, for the first time revealed the major biological processes occurring at different cell cycle phases which provided new insights into the mechanisms regulating the cell cycle and growth of dinoflagellates.

  5. Chloroplast Dysfunction Causes Multiple Defects in Cell Cycle Progression in the Arabidopsis crumpled leaf Mutant

    KAUST Repository

    Hudik, Elodie

    2014-07-18

    The majority of research on cell cycle regulation is focused on the nuclear events that govern the replication and segregation of the genome between the two daughter cells. However, eukaryotic cells contain several compartmentalized organelles with specialized functions, and coordination among these organelles is required for proper cell cycle progression, as evidenced by the isolation of several mutants in which both organelle function and overall plant development were affected. To investigate how chloroplast dysfunction affects the cell cycle, we analyzed the crumpled leaf (crl) mutant of Arabidopsis (Arabidopsis thaliana), which is deficient for a chloroplastic protein and displays particularly severe developmental defects. In the crl mutant, we reveal that cell cycle regulation is altered drastically and that meristematic cells prematurely enter differentiation, leading to reduced plant stature and early endoreduplication in the leaves. This response is due to the repression of several key cell cycle regulators as well as constitutive activation of stress-response genes, among them the cell cycle inhibitor SIAMESE-RELATED5. One unique feature of the crl mutant is that it produces aplastidic cells in several organs, including the root tip. By investigating the consequence of the absence of plastids on cell cycle progression, we showed that nuclear DNA replication occurs in aplastidic cells in the root tip, which opens future research prospects regarding the dialogue between plastids and the nucleus during cell cycle regulation in higher plants.

  6. Two-stage Recognition of Raw Acceleration Signals for 3-D Gesture-Understanding Cell Phones

    OpenAIRE

    Cho, Sung-Jung; Choi, Eunseok; Bang, Won-Chul; YANG Jing; Sohn, Junil; Kim, Dong Yoon; Lee, Young-Bum; Kim, Sangryong

    2006-01-01

    As many functionalities like cameras and MP3 players are converged to cell phones, more intuitive interaction methods are essential beyond tiny keypads. In this paper, we present gesture-based interactions and their two-stage recognition algorithm. Acceleration signals are generated from accelerometer. At the first stage, they are hierarchically modelled and matched as basic component and their relationships by Bayesian networks. At the second stage, they are further classified by SVMs for re...

  7. Non-small cell lung cancer staging: proposed revisions to the TNM system

    OpenAIRE

    Schneider, Bryan J.

    2008-01-01

    Abstract Patients with non-small cell lung cancer (NSCLC) require careful staging at the time of diagnosis to determine prognosis and guide treatment recommendations. The seventh edition of the TNM Classification of Malignant Tumors is scheduled to be published in 2009 and the International Association for the Study of Lung Cancer (IASLC) created the Lung Cancer Staging Project (LCSP) to guide revisions to the current lung cancer staging system. These recommendations will be submitted to the ...

  8. Difference of cell cycle arrests induced by lidamycin in human breast cancer cells.

    Science.gov (United States)

    Liu, Xia; He, Hongwei; Feng, Yun; Zhang, Min; Ren, Kaihuan; Shao, Rongguang

    2006-02-01

    Lidamycin (LDM) is a member of the enediyne antibiotic family. It is undergoing phase I clinical trials in China as a potential chemotherapeutic agent. In the present study, we investigated the mechanism by which LDM induced cell cycle arrest in human breast cancer cells. The results showed that LDM induced G1 arrest in p53 wild-type MCF-7 cells at low concentrations, and caused both G1 and G2/M arrests at higher concentrations. In contrast, LDM induced only G2/M arrest in p53-mutant MCF-7/DOX cells. Western blotting analysis indicated that LDM-induced G1 and G2/M arrests in MCF-7 cells were associated with an increase of p53 and p21, and a decrease of phosphorylated retinoblastoma tumor suppressor protein, cyclin-dependent kinase (Cdk), Cdc2 and cyclin B1 protein levels. However, LDM-induced G2/M arrest in MCF-7/DOX cells was correlated with the reduction of cyclin B1 expression. Further study indicated that the downregulation of cyclin B1 by LDM in MCF-7 cells was associated with decreasing cyclin B1 mRNA levels and promoting protein degradation, whereas it was only due to inducing cyclin B1 protein degradation in MCF-7/DOX cells. In addition, activation of checkpoint kinases Chk1 or Chk2 maybe contributed to LDM-induced cell cycle arrest. Taken together, we provide the first evidence that LDM induces different cell cycle arrests in human breast cancer cells, which are dependent on drug concentration and p53 status. These findings are helpful in understanding the molecular anti-cancer mechanisms of LDM and support its clinical trials. PMID:16428935

  9. The SnSAG merozoite surface antigens of Sarcocystis neurona are expressed differentially during the bradyzoite and sporozoite life cycle stages.

    Science.gov (United States)

    Gautam, A; Dubey, J P; Saville, W J; Howe, D K

    2011-12-29

    Sarcocystis neurona is a two-host coccidian parasite whose complex life cycle progresses through multiple developmental stages differing at morphological and molecular levels. The S. neurona merozoite surface is covered by multiple, related glycosylphosphatidylinositol-linked proteins, which are orthologous to the surface antigen (SAG)/SAG1-related sequence (SRS) gene family of Toxoplasma gondii. Expression of the SAG/SRS proteins in T. gondii and another related parasite Neospora caninum is life-cycle stage specific and seems necessary for parasite transmission and persistence of infection. In the present study, the expression of S. neurona merozoite surface antigens (SnSAGs) was evaluated in the sporozoite and bradyzoite stages. Western blot analysis was used to compare SnSAG expression in merozoites versus sporozoites, while immunocytochemistry was performed to examine expression of the SnSAGs in merozoites versus bradyzoites. These analyses revealed that SnSAG2, SnSAG3 and SnSAG4 are expressed in sporozoites, while SnSAG5 was appeared to be downregulated in this life cycle stage. In S. neurona bradyzoites, it was found that SnSAG2, SnSAG3, SnSAG4 and SnSAG5 were either absent or expression was greatly reduced. As shown for T. gondii, stage-specific expression of the SnSAGs may be important for the parasite to progress through its developmental stages and complete its life cycle successfully. Thus, it is possible that the SAG switching mechanism by these parasites could be exploited as a point of intervention. As well, the alterations in surface antigen expression during different life cycle stages may need to be considered when designing prospective approaches for protective vaccination. PMID:21775062

  10. A Src inhibitor regulates the cell cycle of human pluripotent stem cells and improves directed differentiation

    OpenAIRE

    Chetty, Sundari; Engquist, Elise N.; Mehanna, Elie; Lui, Kathy O.; Tsankov, Alexander M.; Douglas A Melton

    2015-01-01

    Driving human pluripotent stem cells (hPSCs) into specific lineages is an inefficient and challenging process. We show that a potent Src inhibitor, PP1, regulates expression of genes involved in the G1 to S phase transition of the cell cycle, activates proteins in the retinoblastoma family, and subsequently increases the differentiation propensities of hPSCs into all three germ layers. We further demonstrate that genetic suppression of Src regulates the activity of the retinoblastoma protein ...

  11. Influence of cell cycle on responses of MCF-7 cells to benzo[a]pyrene

    Directory of Open Access Journals (Sweden)

    Giddings Ian

    2011-06-01

    Full Text Available Abstract Background Benzo[a]pyrene (BaP is a widespread environmental genotoxic carcinogen that damages DNA by forming adducts. This damage along with activation of the aryl hydrocarbon receptor (AHR induces complex transcriptional responses in cells. To investigate whether human cells are more susceptible to BaP in a particular phase of the cell cycle, synchronised breast carcinoma MCF-7 cells were exposed to BaP. Cell cycle progression was analysed by flow cytometry, DNA adduct formation was assessed by 32P-postlabeling analysis, microarrays of 44K human genome-wide oligos and RT-PCR were used to detect gene expression (mRNA changes and Western blotting was performed to determine the expression of some proteins, including cytochrome P450 (CYP 1A1 and CYP1B1, which are involved in BaP metabolism. Results Following BaP exposure, cells evaded G1 arrest and accumulated in S-phase. Higher levels of DNA damage occurred in S- and G2/M- compared with G0/G1-enriched cultures. Genes that were found to have altered expression included those involved in xenobiotic metabolism, apoptosis, cell cycle regulation and DNA repair. Gene ontology and pathway analysis showed the involvement of various signalling pathways in response to BaP exposure, such as the Catenin/Wnt pathway in G1, the ERK pathway in G1 and S, the Nrf2 pathway in S and G2/M and the Akt pathway in G2/M. An important finding was that higher levels of DNA damage in S- and G2/M-enriched cultures correlated with higher levels of CYP1A1 and CYP1B1 mRNA and proteins. Moreover, exposure of synchronised MCF-7 cells to BaP-7,8-diol-9,10-epoxide (BPDE, the ultimate carcinogenic metabolite of BaP, did not result in significant changes in DNA adduct levels at different phases of the cell cycle. Conclusions This study characterised the complex gene response to BaP in MCF-7 cells and revealed a strong correlation between the varying efficiency of BaP metabolism and DNA damage in different phases of the cell

  12. DNA Damage, Cell Cycle Arrest, and Apoptosis Induction Caused by Lead in Human Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Clement G. Yedjou

    2015-12-01

    Full Text Available In recent years, the industrial use of lead has been significantly reduced from paints and ceramic products, caulking, and pipe solder. Despite this progress, lead exposure continues to be a significant public health concern. The main goal of this research was to determine the in vitro mechanisms of lead nitrate [Pb(NO32] to induce DNA damage, apoptosis, and cell cycle arrest in human leukemia (HL-60 cells. To reach our goal, HL-60 cells were treated with different concentrations of Pb(NO32 for 24 h. Live cells and necrotic death cells were measured by the propidium idiode (PI assay using the cellometer vision. Cell apoptosis was measured by the flow cytometry and DNA laddering. Cell cycle analysis was evaluated by the flow cytometry. The result of the PI demonstrated a significant (p < 0.05 increase of necrotic cell death in Pb(NO32-treated cells, indicative of membrane rupture by Pb(NO32 compared to the control. Data generated from the comet assay indicated a concentration-dependent increase in DNA damage, showing a significant increase (p < 0.05 in comet tail-length and percentages of DNA cleavage. Data generated from the flow cytometry assessment indicated that Pb(NO32 exposure significantly (p < 0.05 increased the proportion of caspase-3 positive cells (apoptotic cells compared to the control. The flow cytometry assessment also indicated Pb(NO32 exposure caused cell cycle arrest at the G0/G1 checkpoint. The result of DNA laddering assay showed presence of DNA smear in the agarose gel with little presence of DNA fragments in the treated cells compared to the control. In summary, Pb(NO32 inhibits HL-60 cells proliferation by not only inducing DNA damage and cell cycle arrest at the G0/G1 checkpoint but also triggering the apoptosis through caspase-3 activation and nucleosomal DNA fragmentation accompanied by secondary necrosis. We believe that our study provides a new insight into the mechanisms of Pb(NO32 exposure and its associated adverse

  13. Palliative Care Intervention in Improving Symptom Control and Quality of Life in Patients With Stage II-IV Non-small Cell Lung Cancer and Their Family Caregivers

    Science.gov (United States)

    2016-04-06

    Caregiver; Psychological Impact of Cancer and Its Treatment; Recurrent Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  14. Dynamics of the cell-cycle network under genome-rewiring perturbations

    International Nuclear Information System (INIS)

    The cell-cycle progression is regulated by a specific network enabling its ordered dynamics. Recent experiments supported by computational models have shown that a core of genes ensures this robust cycle dynamics. However, much less is known about the direct interaction of the cell-cycle regulators with genes outside of the cell-cycle network, in particular those of the metabolic system. Following our recent experimental work, we present here a model focusing on the dynamics of the cell-cycle core network under rewiring perturbations. Rewiring is achieved by placing an essential metabolic gene exclusively under the regulation of a cell-cycle's promoter, forcing the cell-cycle network to function under a multitasking challenging condition; operating in parallel the cell-cycle progression and a metabolic essential gene. Our model relies on simple rate equations that capture the dynamics of the relevant protein–DNA and protein–protein interactions, while making a clear distinction between these two different types of processes. In particular, we treat the cell-cycle transcription factors as limited ‘resources’ and focus on the redistribution of resources in the network during its dynamics. This elucidates the sensitivity of its various nodes to rewiring interactions. The basic model produces the correct cycle dynamics for a wide range of parameters. The simplicity of the model enables us to study the interface between the cell-cycle regulation and other cellular processes. Rewiring a promoter of the network to regulate a foreign gene, forces a multitasking regulatory load. The higher the load on the promoter, the longer is the cell-cycle period. Moreover, in agreement with our experimental results, the model shows that different nodes of the network exhibit variable susceptibilities to the rewiring perturbations. Our model suggests that the topology of the cell-cycle core network ensures its plasticity and flexible interface with other cellular processes

  15. Ras signalling linked to the cell-cycle machinery by the retinoblastoma protein

    NARCIS (Netherlands)

    Peeper, D.S.; Upton, T.M.; Ladha, M.H.; Neuman, E.; Zalvide, J.; Bernards, R.A.; DeCaprio, J.A.; Ewen, M.E.

    1997-01-01

    The Ras proto-oncogene is a central component of mitogenic signal-transduction pathways, and is essential for cells both to leave a quiescent state (GO) and to pass through the GI/S transition of the cell cycle. The mechanism by which Ras signalling regulates cell-cycle progression is unclear, howev

  16. Scaffolding during the cell cycle by A-kinase anchoring proteins

    NARCIS (Netherlands)

    Han, B; Poppinga, W J; Schmidt, M

    2015-01-01

    Cell division relies on coordinated regulation of the cell cycle. A process including a well-defined series of strictly regulated molecular mechanisms involving cyclin-dependent kinases, retinoblastoma protein, and polo-like kinases. Dysfunctions in cell cycle regulation are associated with disease

  17. Altered cell cycle regulation helps stem-like carcinoma cells resist apoptosis

    OpenAIRE

    Dalton Stephen; Chappell James

    2010-01-01

    Abstract Reemergence of carcinomas following chemotherapy and/or radiotherapy is not well understood, but a recent study in BMC Cancer suggests that resistance to apoptosis resulting from altered cell cycle regulation is crucial. See research article: http://biomedcentral.com/1471-2407/10/166

  18. Cell cycle perturbations induced by Cisplatin in normal and tumor transformed cells

    Czech Academy of Sciences Publication Activity Database

    Mareš, Vladislav; Mazzini, G.; Lisá, Věra; Ferrari, C.; Malík, Radek; Šedo, A.

    2001-01-01

    Roč. 5, - (2001), s. 23-29. ISSN 1212-3137 Grant ostatní: GA UK(XC) 58/1999/C; LF UK(XC) 206019-2-"Oncology" Institutional research plan: CEZ:AV0Z5011922 Keywords : cell cycle * cisplatin * DNA content Subject RIV: FD - Oncology ; Hematology

  19. Platinum(IV) complex LA-12 causes cell cycle perturbations and apoptosis in colon carcinoma cells

    Czech Academy of Sciences Publication Activity Database

    Blanářová, Olga; Jendželovský, R.; Jelínková, I.; Souček, Karel; Hofmanová, Jiřina; Sova, P.; Kozubík, Alois

    Budapest, 2008. s. 181. [ISAC XXIV International Congress, Cytometry in the Age of Systems Biology. 17.05.2008-21.05.2008, Budapest] R&D Projects: GA ČR(CZ) GA301/07/1557 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : platinum drugs * cell cycle * apoptosis Subject RIV: BO - Biophysics

  20. Polyamine metabolism during the cell cycle of synchronized tobacco BY-2 cell line

    Czech Academy of Sciences Publication Activity Database

    Gemperlová, Lenka; Cvikrová, Milena; Fischerová, Lucie; Binarová, Pavla; Fischer, L.; Eder, Josef

    2009-01-01

    Roč. 47, č. 7 (2009), s. 584-591. ISSN 0981-9428 R&D Projects: GA AV ČR IAA500200719 Institutional research plan: CEZ:AV0Z50380511; CEZ:AV0Z50200510 Keywords : ADC * Cell cycle * DAO Subject RIV: EF - Botanics Impact factor: 2.485, year: 2009

  1. Reactors for heat production with good electrical generating efficiency. Recovery of heat in helium-cooled direct-cycle reactors with one or two compression stages

    International Nuclear Information System (INIS)

    In order to be realistic, an evaluation of the performance of helium-cooled direct-cycle reactors must be based on a preliminary study of the circuits and the architecture. This was the procedure adopted by the Department of Mechanical and Thermal Studies (Saclay Nuclear Research Centre) which recently developed a plant concept aimed at solving the various problems involved and also defined the sizes of the principal components. The circuits have been designed to obtain a good electrical generating efficiency but without prejudicing this it has also been attempted to obtain the best conditions for recovering heat from the coolants. Results are presented for the following cases: a two-compression-stage cycle with good electrical generating efficiency and non-preferential heat recovery; a two-compression-stage cycle with acceptable electrical generating efficiency and improved heat recovery; a single-compression-stage cycle for the production of electricity with recovery of heat in the form of hot water; a single-compression-stage cycle with large-scale production of heat in the form of steam and hot water. It appears that the characteristics of the hot water in the secondary recovery circuits are well suited to district heating. It should be noted that the overall performances of all the different variants are satisfactory for a helium temperature at the core outlet of 8000C, which is reasonable. (author)

  2. Diagnosis, staging and treatment of patients with non-small cell lung cancer for the surgeon

    OpenAIRE

    Bryant, Ayesha S.; Cerfolio, Robert J.

    2009-01-01

    This article covers the risk factors, diagnostic tools, staging methods/modalities and treatment for patients with non-small cell lung cancer (NSCLC). Also presented is the new 7th edition American Joint Cancer Committee (AJCC) TNM classification for staging of NSCLC and a recommended treatment algorithm.

  3. Backup pathways of NHEJ in cells of higher eukaryotes: Cell cycle dependence

    International Nuclear Information System (INIS)

    DNA double-strand breaks (DSBs) induced by ionizing radiation (IR) in cells of higher eukaryotes are predominantly repaired by a pathway of non-homologous end joining (NHEJ) utilizing Ku, DNA-PKcs, DNA ligase IV, XRCC4 and XLF/Cernunnos (D-NHEJ) as central components. Work carried out in our laboratory and elsewhere shows that when this pathway is chemically or genetically compromised, cells do not shunt DSBs to homologous recombination repair (HRR) but instead use another form of NHEJ operating as a backup (B-NHEJ). Here I review our efforts to characterize this repair pathway and discuss its dependence on the cell cycle as well as on the growth conditions. I present evidence that B-NHEJ utilizes ligase III, PARP-1 and histone H1. When B-NHEJ is examined throughout the cell cycle, significantly higher activity is observed in G2 phase that cannot be attributed to HRR. Furthermore, the activity of B-NHEJ is compromised when cells enter the plateau phase of growth. Together, these observations uncover a repair pathway with unexpected biochemical constitution and interesting cell cycle and growth factor regulation. They generate a framework for investigating the mechanistic basis of HRR contribution to DSB repair.

  4. Backup pathways of NHEJ in cells of higher eukaryotes: cell cycle dependence.

    Science.gov (United States)

    Iliakis, George

    2009-09-01

    DNA double-strand breaks (DSBs) induced by ionizing radiation (IR) in cells of higher eukaryotes are predominantly repaired by a pathway of non-homologous end joining (NHEJ) utilizing Ku, DNA-PKcs, DNA ligase IV, XRCC4 and XLF/Cernunnos (D-NHEJ) as central components. Work carried out in our laboratory and elsewhere shows that when this pathway is chemically or genetically compromised, cells do not shunt DSBs to homologous recombination repair (HRR) but instead use another form of NHEJ operating as a backup (B-NHEJ). Here I review our efforts to characterize this repair pathway and discuss its dependence on the cell cycle as well as on the growth conditions. I present evidence that B-NHEJ utilizes ligase III, PARP-1 and histone H1. When B-NHEJ is examined throughout the cell cycle, significantly higher activity is observed in G2 phase that cannot be attributed to HRR. Furthermore, the activity of B-NHEJ is compromised when cells enter the plateau phase of growth. Together, these observations uncover a repair pathway with unexpected biochemical constitution and interesting cell cycle and growth factor regulation. They generate a framework for investigating the mechanistic basis of HRR contribution to DSB repair. PMID:19604590

  5. Trichostatin A Regulates hGCN5 Expression and Cell Cycle on Daudi Cells in vitro

    Institute of Scientific and Technical Information of China (English)

    LIU Hongli; CHEN Yan; CUI Guohui; WU Gang; WANG Tao; HU Jianli

    2006-01-01

    The expression of human general control of amino acid synthesis protein 5 (hGCN5) in human Burkitt's lymphoma Daudi cells in vitro, effects of Trichostatin A (TSA) on cell proliferation and apoptosis and the molecular mechanism of TSA inhibiting proliferation of Daudi cells were investigated. The effects of TSA on the growth of Daudi cells were studied by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. The effect of TSA on the cell cycle of Daudi cells was assayed by a propidium iodide method. Immunochemistry and Western blot were used to detect the expression of hGCN5. The proliferation of Daudi cells was decreased in TSA-treated group with a 24 h IC50 value of 415.3979 μg/L. TSA induced apoptosis of Daudi cells in a time- and dose-dependent manner. Treatment with TSA (200 and 400 μg/L) for 24 h, the apoptosis rates of Daudi cells were (14.74±2.04) % and (17.63±1.25) %, respectively. The cell cycle was arrested in G0/G1 phase (50, 100 μtg/L) and in G2/M phase (200 μg/L) by treatment with TSA for 24 h.The expression of hGCN5 protein in Daudi cells was increased in 24 h TSA-treated group by immunochemistry and Western blot (P<0.05). It was suggested that TSA as HDACIs could increase the expression of hGCN5 in Daudi cells, and might play an important role in regulating the proliferation and apoptosis of B-NHL cell line Daudi cells.

  6. Apoptosis and cell-cycle arrest in human and murine tumor cells are initiated by isoprenoids.

    Science.gov (United States)

    Mo, H; Elson, C E

    1999-04-01

    Diverse classes of phytochemicals initiate biological responses that effectively lower cancer risk. One class of phytochemicals, broadly defined as pure and mixed isoprenoids, encompasses an estimated 22,000 individual components. A representative mixed isoprenoid, gamma-tocotrienol, suppresses the growth of murine B16(F10) melanoma cells, and with greater potency, the growth of human breast adenocarcinoma (MCF-7) and human leukemic (HL-60) cells. beta-Ionone, a pure isoprenoid, suppresses the growth of B16 cells and with greater potency, the growth of MCF-7, HL-60 and human colon adenocarcinoma (Caco-2) cells. Results obtained with diverse cell lines differing in ras and p53 status showed that the isoprenoid-mediated suppression of growth is independent of mutated ras and p53 functions. beta-Ionone suppressed the growth of human colon fibroblasts (CCD-18Co) but only when present at three-fold the concentration required to suppress the growth of Caco-2 cells. The isoprenoids initiated apoptosis and, concomitantly arrested cells in the G1 phase of the cell cycle. Both suppress 3-hydroxy-3-methylglutaryl CoA reductase activity. beta-Ionone and lovastatin interfered with the posttranslational processing of lamin B, an activity essential to assembly of daughter nuclei. This interference, we postulate, renders neosynthesized DNA available to the endonuclease activities leading to apoptotic cell death. Lovastatin-imposed mevalonate starvation suppressed the glycosylation and translocation of growth factor receptors to the cell surface. As a consequence, cells were arrested in the G1 phase of the cell cycle. This rationale may apply to the isoprenoid-mediated G1-phase arrest of tumor cells. The additive and potentially synergistic actions of these isoprenoids in the suppression of tumor cell proliferation and initiation of apoptosis coupled with the mass action of the diverse isoprenoid constituents of plant products may explain, in part, the impact of fruit, vegetable

  7. Slow-cycling stem cells in hydra contribute to head regeneration

    Directory of Open Access Journals (Sweden)

    Niraimathi Govindasamy

    2014-11-01

    Full Text Available Adult stem cells face the challenge of maintaining tissue homeostasis by self-renewal while maintaining their proliferation potential over the lifetime of an organism. Continuous proliferation can cause genotoxic/metabolic stress that can compromise the genomic integrity of stem cells. To prevent stem cell exhaustion, highly proliferative adult tissues maintain a pool of quiescent stem cells that divide only in response to injury and thus remain protected from genotoxic stress. Hydra is a remarkable organism with highly proliferative stem cells and ability to regenerate at whole animal level. Intriguingly, hydra does not display consequences of high proliferation, such as senescence or tumour formation. In this study, we investigate if hydra harbours a pool of slow-cycling stem cells that could help prevent undesirable consequences of continuous proliferation. Hydra were pulsed with the thymidine analogue 5-ethynyl-2′-deoxyuridine (EdU and then chased in the absence of EdU to monitor the presence of EdU-retaining cells. A significant number of undifferentiated cells of all three lineages in hydra retained EdU for about 8–10 cell cycles, indicating that these cells did not enter cell cycle. These label-retaining cells were resistant to hydroxyurea treatment and were predominantly in the G2 phase of cell cycle. Most significantly, similar to mammalian quiescent stem cells, these cells rapidly entered cell division during head regeneration. This study shows for the first time that, contrary to current beliefs, cells in hydra display heterogeneity in their cell cycle potential and the slow-cycling cells in this population enter cell cycle during head regeneration. These results suggest an early evolution of slow-cycling stem cells in multicellular animals.

  8. Slow-cycling stem cells in hydra contribute to head regeneration.

    Science.gov (United States)

    Govindasamy, Niraimathi; Murthy, Supriya; Ghanekar, Yashoda

    2014-01-01

    Adult stem cells face the challenge of maintaining tissue homeostasis by self-renewal while maintaining their proliferation potential over the lifetime of an organism. Continuous proliferation can cause genotoxic/metabolic stress that can compromise the genomic integrity of stem cells. To prevent stem cell exhaustion, highly proliferative adult tissues maintain a pool of quiescent stem cells that divide only in response to injury and thus remain protected from genotoxic stress. Hydra is a remarkable organism with highly proliferative stem cells and ability to regenerate at whole animal level. Intriguingly, hydra does not display consequences of high proliferation, such as senescence or tumour formation. In this study, we investigate if hydra harbours a pool of slow-cycling stem cells that could help prevent undesirable consequences of continuous proliferation. Hydra were pulsed with the thymidine analogue 5-ethynyl-2'-deoxyuridine (EdU) and then chased in the absence of EdU to monitor the presence of EdU-retaining cells. A significant number of undifferentiated cells of all three lineages in hydra retained EdU for about 8-10 cell cycles, indicating that these cells did not enter cell cycle. These label-retaining cells were resistant to hydroxyurea treatment and were predominantly in the G2 phase of cell cycle. Most significantly, similar to mammalian quiescent stem cells, these cells rapidly entered cell division during head regeneration. This study shows for the first time that, contrary to current beliefs, cells in hydra display heterogeneity in their cell cycle potential and the slow-cycling cells in this population enter cell cycle during head regeneration. These results suggest an early evolution of slow-cycling stem cells in multicellular animals. PMID:25432513

  9. An integrative model and analysis of cell cycle in fission yeast

    Institute of Scientific and Technical Information of China (English)

    TENG Hu; HUANG Xun; XIU Zhilong; FENG Enmin

    2005-01-01

    According to the recent investigation on cell cycle of fission yeast, a mathematical dynamic model is formulated. Four cyclins, e.g. Puc1, Cig1, Cig2 and Cdc13, are investigated here. The interacting networks between the cyclins and the process of cell cycle are mathematically described. The functions of these cyclins are particularly analyzed. Comparison among different mutants indicates that the cyclins play an important role in cell cycle.

  10. CRL4Cdt2: Master coordinator of cell cycle progression and genome stability

    OpenAIRE

    Abbas, Tarek; Dutta, Anindya

    2011-01-01

    Polyubiquitin-mediated degradation of proteins plays an essential role in various physiological processes including cell cycle progression, transcription and DNA replication and repair. Increasing evidence supports a vital role for the E3 ubiquitin ligase cullin-4, in conjunction with the substrate recognition factor Cdt2 (CRL4Cdt2), for the degradation of multiple cell cycle-regulated proteins to prevent genomic instability. In addition, it is critical for normal cell cycle progression by en...

  11. The Oxygen-Rich Postnatal Environment Induces Cardiomyocyte Cell-Cycle Arrest through DNA Damage Response

    OpenAIRE

    Bao\\xa0N. Puente; Wataru Kimura; Shalini\\xa0A. Muralidhar; Jesung Moon; James\\xa0F. Amatruda; Kate\\xa0L. Phelps; David Grinsfelder; Beverly\\xa0A. Rothermel; Rui Chen; Joseph\\xa0A. Garcia; Celio\\xa0X. Santos; SuWannee Thet; Eiichiro Mori; Michael\\xa0T. Kinter; Paul\\xa0M. Rindler

    2014-01-01

    The mammalian heart has a remarkable regenerative capacity for a short period of time after birth, after which the majority of cardiomyocytes permanently exit cell cycle. We sought to determine the primary post-natal event that results in cardiomyocyte cell-cycle arrest. We hypothesized that transition to the oxygen rich postnatal environment is the upstream signal that results in cell cycle arrest of cardiomyocytes. Here we show that reactive oxygen species (ROS), oxidative DNA damage, and D...

  12. Cell Cycle Synchrony in Giardia intestinalis Cultures Achieved by Using Nocodazole and Aphidicolin▿

    OpenAIRE

    Poxleitner, Marianne K.; Dawson, Scott C.; Cande, W. Zacheus

    2008-01-01

    Giardia intestinalis is a ubiquitous intestinal protozoan parasite and has been proposed to represent the earliest diverging lineage of extant eukaryotes. Despite the importance of Giardia as a model organism, research on Giardia has been hampered by an inability to achieve cell cycle synchrony for in vitro cultures. This report details successful methods for attaining cell cycle synchrony in Giardia cultures. The research presented here demonstrates reversible cell cycle arrest in G1/S and G...

  13. DNA Damage and Cell Cycle Arrest Induced by Protoporphyrin IX in Sarcoma 180 Cells

    Directory of Open Access Journals (Sweden)

    Qing Li

    2013-09-01

    Full Text Available Background: Porphyrin derivatives have been widely used in photodynamic therapy as effective sensitizers. Protoporphyrin IX (PpIX, a well-known hematoporphyrin derivative component, shows great potential to enhance light induced tumor cell damage. However, PpIX alone could also exert anti-tumor effects. The mechanisms underlying those direct effects are incompletely understood. This study thus investigated the putative mechanisms underlying the anti-tumor effects of PpIX on sarcoma 180 (S180 cells. Methods: S180 cells were treated with different concentrations of PpIX. Following the treatment, cell viability was evaluated by the 3-(4, 5- dimethylthiazol-2-yl-2, 5-diphenyltetrazoliumbromide (MTT assay; Disruption of mitochondrial membrane potential was measured by flow cytometry; The trans-location of apoptosis inducer factor (AIF from mitochondria to nucleus was visualized by confocal laser scanning microscopy; DNA damage was detected by single cell gel electrophoresis; Cell cycle distribution was analyzed by DNA content with flow cytometry; Cell cycle associated proteins were detected by western blotting. Results: PpIX (≥ 1 µg/ml significantly inhibited proliferation and reduced viability of S180 cells in a dose-dependent manner. PpIX rapidly and significantly triggered mitochondrial membrane depolarization, AIF (apoptosis inducer factor translocation from mitochondria to nucleus and DNA damage, effects partially relieved by the specific inhibitor of MPTP (mitochondrial permeability transition pore. Furthermore, S phase arrest and upregulation of the related proteins of P53 and P21 were observed following 12 and 24 h PpIX exposure. Conclusion: PpIX could inhibit tumor cell proliferation by induction of DNA damage and cell cycle arrest in the S phase.

  14. Isolation of austroinulin possessing cell cycle inhibition activity from Blumea glomerata and revision of its absolute configuration.

    Science.gov (United States)

    Ohtsuki, Takashi; Koyano, Takashi; Kowithayakorn, Thaworn; Yamaguchi, Naoto; Ishibashi, Masami

    2004-12-01

    A labdane-diterpene, austroinulin (1), together with several known flavonoids and sesquiterpenes were isolated from leaves of Blumea glomerata (Compositae). Austroinulin (1) and most of the flavonoids showed cytotoxicity against HeLa cells, while austroinulin (1) exhibited a cell cycle inhibition effect at the G1 stage at the concentration of 15.2 microg/mL (47.2 microM). The absolute configuration of 1 was revised as 5S,6R,7S,8S,9R,10R on the basis of the modified Mosher's method. PMID:15643553

  15. Interim PET After Two ABVD Cycles in Early-Stage Hodgkin Lymphoma: Outcomes Following the Continuation of Chemotherapy Plus Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Simontacchi, Gabriele [Radiotherapy Unit, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence (Italy); Filippi, Andrea Riccardo, E-mail: andreariccardo.filippi@unito.it [Department of Oncology, University of Torino, Torino (Italy); Ciammella, Patrizia [Radiation Oncology Unit, Department of Advanced Technology, Arcispedale Santa Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia (Italy); Buglione, Michela [Radiation Oncology Department, University and Spedali Civili, Brescia (Italy); Saieva, Calogero [Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence (Italy); Magrini, Stefano Maria [Radiation Oncology Department, University and Spedali Civili, Brescia (Italy); Livi, Lorenzo [Radiotherapy Unit, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence (Italy); Iotti, Cinzia [Radiation Oncology Unit, Department of Advanced Technology, Arcispedale Santa Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia (Italy); Botto, Barbara [Hematology Unit, Città della Salute e della Scienza Hospital, Torino (Italy); Vaggelli, Luca [Nuclear Medicine Department, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence (Italy); Re, Alessandro [Hematology Unit, University and Spedali Civili, Brescia (Italy); Merli, Francesco [Hematology Unit, Arcispedale Santa Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia (Italy); Ricardi, Umberto [Department of Oncology, University of Torino, Torino (Italy)

    2015-08-01

    Purpose: This multicenter retrospective study was designed to evaluate the prognostic role of interim fluorodeoxyglucose-labeled positron emission tomography (i-FDG-PET) in a cohort of patients affected with early-stage Hodgkin lymphoma (HL) treated initially with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by radiation therapy, and to assess the role of chemotherapy continuation plus radiation therapy for i-FDG-PET-positive patients. Methods and Materials: Data from 257 patients were retrieved from 4 hematology and radiation oncology departments. Inclusion criteria were stage I to IIAB HL, “intention-to-treat” AVBD plus radiation therapy, and FDG-PET at diagnosis and after the first 2 ABVD cycles. All i-FDG-PET scans underwent blinded local review by using the Deauville 5-point scoring system; patients were stratified as negative or positive using 2 Deauville score cutoff values, ≥3 or ≥4. Results: Median follow-up time was 56 months (range: 9-163 months); 5-year overall survival (OS) and disease-specific survival (DSS) for the whole cohort were 97.5% and 98.3%, respectively. Five-year progression-free survival (PFS) was 95.6%. After i-FDG-PET revision, 43 of 257 patients (16.7%) had a positive i-FDG-PET (Deauville scores: 3-5). Five-year PFS rates for i-FDG-PET-negative and i-FDG-PET-positive patients were 98.1% and 83.7%, respectively, if using a Deauville score cutoff of 3, and 97.7% and 78.6%, respectively, if using a cutoff of 4 (P=.0001). Five-year OS for i-FDG-PET-negative and i-FDG-PET-positive patients was 98.5% and 93.0%, respectively, if using a cutoff of 3, and 98.6% and 89.3%, respectively, if using a cutoff of 4 (P=.029 and P=.002). At univariate regression analysis, i-FDG-PET positivity was associated with worse OS and PFS. At multivariate analysis, performed only for PFS, i-FDG-PET positivity confirmed its negative impact (P=.002). Conclusions: i-FDG-PET is prognostic for PFS and OS in early-stage HL

  16. Interim PET After Two ABVD Cycles in Early-Stage Hodgkin Lymphoma: Outcomes Following the Continuation of Chemotherapy Plus Radiotherapy

    International Nuclear Information System (INIS)

    Purpose: This multicenter retrospective study was designed to evaluate the prognostic role of interim fluorodeoxyglucose-labeled positron emission tomography (i-FDG-PET) in a cohort of patients affected with early-stage Hodgkin lymphoma (HL) treated initially with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by radiation therapy, and to assess the role of chemotherapy continuation plus radiation therapy for i-FDG-PET-positive patients. Methods and Materials: Data from 257 patients were retrieved from 4 hematology and radiation oncology departments. Inclusion criteria were stage I to IIAB HL, “intention-to-treat” AVBD plus radiation therapy, and FDG-PET at diagnosis and after the first 2 ABVD cycles. All i-FDG-PET scans underwent blinded local review by using the Deauville 5-point scoring system; patients were stratified as negative or positive using 2 Deauville score cutoff values, ≥3 or ≥4. Results: Median follow-up time was 56 months (range: 9-163 months); 5-year overall survival (OS) and disease-specific survival (DSS) for the whole cohort were 97.5% and 98.3%, respectively. Five-year progression-free survival (PFS) was 95.6%. After i-FDG-PET revision, 43 of 257 patients (16.7%) had a positive i-FDG-PET (Deauville scores: 3-5). Five-year PFS rates for i-FDG-PET-negative and i-FDG-PET-positive patients were 98.1% and 83.7%, respectively, if using a Deauville score cutoff of 3, and 97.7% and 78.6%, respectively, if using a cutoff of 4 (P=.0001). Five-year OS for i-FDG-PET-negative and i-FDG-PET-positive patients was 98.5% and 93.0%, respectively, if using a cutoff of 3, and 98.6% and 89.3%, respectively, if using a cutoff of 4 (P=.029 and P=.002). At univariate regression analysis, i-FDG-PET positivity was associated with worse OS and PFS. At multivariate analysis, performed only for PFS, i-FDG-PET positivity confirmed its negative impact (P=.002). Conclusions: i-FDG-PET is prognostic for PFS and OS in early-stage HL

  17. Morphological and proteomic analysis of early stage of osteoblast differentiation in osteoblastic progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Dun [Population Council, 1230 York Avenue, New York, NY 10065 (United States); Orthopedic Department, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang 317000 (China); Chen, Hai-Xiao, E-mail: Hxchen-1@163.net [Orthopedic Department, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang 317000 (China); Yu, Hai-Qiang [Proteomics Resource Center, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Liang, Yong; Wang, Carrie [Population Council, 1230 York Avenue, New York, NY 10065 (United States); Lian, Qing-Quan [The 2nd Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325000 (China); Deng, Hai-Teng, E-mail: dengh@mail.rockefeller.edu [Proteomics Resource Center, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Ge, Ren-Shan, E-mail: rge@popcbr.rockefeller.edu [Population Council, 1230 York Avenue, New York, NY 10065 (United States); The 2nd Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325000 (China)

    2010-08-15

    Bone remodeling relies on a dynamic balance between bone formation and resorption, mediated by osteoblasts and osteoclasts, respectively. Under certain stimuli, osteoprogenitor cells may differentiate into premature osteoblasts and further into mature osteoblasts. This process is marked by increased alkaline phosphatase (ALP) activity and mineralized nodule formation. In this study, we induced osteoblast differentiation in mouse osteoprogenitor MC3T3-E1 cells and divided the process into three stages. In the first stage (day 3), the MC3T3-E1 cell under osteoblast differentiation did not express ALP or deposit a mineralized nodule. In the second stage, the MC3T3-E1 cell expressed ALP but did not form a mineralized nodule. In the third stage, the MC3T3-E1 cell had ALP activity and formed mineralized nodules. In the present study, we focused on morphological and proteomic changes of MC3T3-E1 cells in the early stage of osteoblast differentiation - a period when premature osteoblasts transform into mature osteoblasts. We found that mean cell area and mean stress fiber density were increased in this stage due to enhanced cell spreading and decreased cell proliferation. We further analyzed the proteins in the signaling pathway of regulation of the cytoskeleton using a proteomic approach and found upregulation of IQGAP1, gelsolin, moesin, radixin, and Cfl1. After analyzing the focal adhesion signaling pathway, we found the upregulation of FLNA, LAMA1, LAMA5, COL1A1, COL3A1, COL4A6, and COL5A2 as well as the downregulation of COL4A1, COL4A2, and COL4A4. In conclusion, the signaling pathway of regulation of the cytoskeleton and focal adhesion play critical roles in regulating cell spreading and actin skeleton formation in the early stage of osteoblast differentiation.

  18. Adhesion of different cell cycle human hepatoma cells to endothelial cells and roles of integrin β1

    Institute of Scientific and Technical Information of China (English)

    Guan-Bin Song; Jian Qin; Qing Luo; Xiao-Dong Shen; Run-Bin Yan; Shao-Xi Cai

    2005-01-01

    AIM: To investigate the adhesive mechanical properties of different cell cycle human hepatoma cells (SMMC-7721)to human umbilical vein endothelial cells (ECV-304),expression of adhesive molecule integrinβ1 in SMMC-7721cells and its contribution to this adhesive course.METHODS: Adhesive force of SMMC-7721 cells to endothelialcells was measured using micropipette aspiration technique.Synchronous G1 and S phase SMMC-7721 cells wereachieved by thymine-2-deoxyriboside and colchicinessequential blockage method and double thymine-2-deoxyriboside blockage method, respectively. Synchronousrates of SMMC-7721 cells and expression of integrinβ1 inSMMC-7721 cells were detected by flow cytometer.RESULTS: The percentage of cell cycle phases of generalSMMC-7721 cells was 11.01% in G2/M phases, 53.51% inG0/G1 phase, and 35.48% in S phase. The synchronous ratesof G1 and S phase SMMC-7721 cells amounted to 74.09%and 98.29%, respectively. The adhesive force of SMMC-7721cells to endothelial cells changed with the variations ofadhesive time and presented behavior characteristics ofadhesion and de-adhesion. S phase SMMC-7721 cells had higheradhesive forces than G1 phase cells [(307.65±92.10)× 10-10Nvs (195.42±60.72)×10-10N, P<0.01]. The expressivefluorescent intensity of integrinβ1 in G1 phase SMMC-7721cells was depressed more significantly than the values ofS phase and general SMMC-7721cells. The contribution ofadhesive integrinβ1 was about 53% in this adhesive course.CONCLUSION: SMMC-7721 cells can be synchronizedpreferably in G1 and S phases with thymine-2-deoxyribosideand colchicines. The adhesive molecule integrinβ1 expressesa high level in SMMC-7721 cells and shows differences invarious cell cycles, suggesting integrin β1 plays an importantrole in adhesion to endothelial cells. The change of adhesiveforces in different cell cycle SMMC-7721 cells indicatesthat S phase cells play predominant roles possibly whilethey interact with endothelial cells.

  19. Replication of the R6K plasmid during the Escherichia coli cell cycle.

    OpenAIRE

    Keasling, J.D.; Palsson, B O; Cooper, S.

    1992-01-01

    The cell-cycle replication pattern of the R6K plasmid has been investigated by using the membrane-elution technique to produce cells labelled at different times during the division cycle and scintillation counting for quantitative analysis of radioactive plasmid DNA. The high-copy plasmid R6K replicates exponentially in a cell-cycle-independent manner. A mini-R6K plasmid deleted for the ori alpha origin of replication also replicates, exponentially in a cell-cycle-independent manner.

  20. A generalized model for multi-marker analysis of cell cycle progression in synchrony experiments

    OpenAIRE

    Mayhew, Michael B.; Joshua W. Robinson; Jung, Boyoun; Haase, Steven B.; Alexander J Hartemink

    2011-01-01

    Motivation: To advance understanding of eukaryotic cell division, it is important to observe the process precisely. To this end, researchers monitor changes in dividing cells as they traverse the cell cycle, with the presence or absence of morphological or genetic markers indicating a cell's position in a particular interval of the cell cycle. A wide variety of marker data is available, including information-rich cellular imaging data. However, few formal statistical methods have been develop...

  1. Bach1 Induces Endothelial Cell Apoptosis and Cell-Cycle Arrest through ROS Generation

    Science.gov (United States)

    Wang, Xinhong; Liu, Junxu; Jiang, Li; Wei, Xiangxiang; Niu, Cong; Wang, Rui; Zhang, Jianyi; Yao, Kang

    2016-01-01

    The transcription factor BTB and CNC homology 1 (Bach1) regulates genes involved in the oxidative stress response and cell-cycle progression. We have recently shown that Bach1 impairs cell proliferation and promotes apoptosis in cultured endothelial cells (ECs), but the underlying mechanisms are largely uncharacterized. Here we demonstrate that Bach1 upregulation impaired the blood flow recovery from hindlimb ischemia and this effect was accompanied both by increases in reactive oxygen species (ROS) and cleaved caspase 3 levels and by declines in the expression of cyclin D1 in the injured tissues. We found that Bach1 overexpression induced mitochondrial ROS production and caspase 3-dependent apoptosis and its depletion attenuated H2O2-induced apoptosis in cultured human microvascular endothelial cells (HMVECs). Bach1-induced apoptosis was largely abolished when the cells were cultured with N-acetyl-l-cysteine (NAC), a ROS scavenger. Exogenous expression of Bach1 inhibited the cell proliferation and the expression of cyclin D1, induced an S-phase arrest, and increased the expression of cyclin E2, which were partially blocked by NAC. Taken together, our results suggest that Bach1 suppresses cell proliferation and induces cell-cycle arrest and apoptosis by increasing mitochondrial ROS production, suggesting that Bach1 may be a promising treatment target for the treatment of vascular diseases. PMID:27057283

  2. A high-resolution transcriptome map of cell cycle reveals novel connections between periodic genes and cancer.

    Science.gov (United States)

    Dominguez, Daniel; Tsai, Yi-Hsuan; Gomez, Nicholas; Jha, Deepak Kumar; Davis, Ian; Wang, Zefeng

    2016-08-01

    Progression through the cell cycle is largely dependent on waves of periodic gene expression, and the regulatory networks for these transcriptome dynamics have emerged as critical points of vulnerability in various aspects of tumor biology. Through RNA-sequencing of human cells during two continuous cell cycles (>2.3 billion paired reads), we identified over 1 000 mRNAs, non-coding RNAs and pseudogenes with periodic expression. Periodic transcripts are enriched in functions related to DNA metabolism, mitosis, and DNA damage response, indicating these genes likely represent putative cell cycle regulators. Using our set of periodic genes, we developed a new approach termed "mitotic trait" that can classify primary tumors and normal tissues by their transcriptome similarity to different cell cycle stages. By analyzing >4 000 tumor samples in The Cancer Genome Atlas (TCGA) and other expression data sets, we found that mitotic trait significantly correlates with genetic alterations, tumor subtype and, notably, patient survival. We further defined a core set of 67 genes with robust periodic expression in multiple cell types. Proteins encoded by these genes function as major hubs of protein-protein interaction and are mostly required for cell cycle progression. The core genes also have unique chromatin features including increased levels of CTCF/RAD21 binding and H3K36me3. Loss of these features in uterine and kidney cancers is associated with altered expression of the core 67 genes. Our study suggests new chromatin-associated mechanisms for periodic gene regulation and offers a predictor of cancer patient outcomes. PMID:27364684

  3. Multimodality Therapy for Limited-Stage Small-Cell Lung Cancer.

    Science.gov (United States)

    Almquist, Daniel; Mosalpuria, Kailash; Ganti, Apar Kishor

    2016-02-01

    Limited-stage small-cell lung cancer (SCLC) occurs in only one third of patients with SCLC, but it is potentially curable. Combined-modality therapy (chemotherapy and radiotherapy) has long been the mainstay of therapy for this condition, but more recent data suggest a role for surgery in early-stage disease. Prophylactic cranial irradiation seems to improve outcomes in patients who have responded to initial therapy. This review addresses the practical aspects of staging and treatment of patients with limited-stage SCLC. PMID:26869647

  4. Ethanol extract of Innotus obliquus (Chaga mushroom) induces G1 cell cycle arrest in HT-29 human colon cancer cells

    OpenAIRE

    Lee, Hyun Sook; Kim, Eun Ji; Kim, Sun Hyo

    2015-01-01

    BACKGROUND/OBJECTIVES Inonotus obliquus (I. obliquus, Chaga mushroom) has long been used as a folk medicine to treat cancer. In the present study, we examined whether or not ethanol extract of I. obliquus (EEIO) inhibits cell cycle progression in HT-29 human colon cancer cells, in addition to its mechanism of action. MATERIALS/METHODS To examine the effects of Inonotus obliquus on the cell cycle progression and the molecular mechanism in colon cancer cells, HT-29 human colon cancer cells were...

  5. Radiation tolerance in the fruit fly, Drosophila Melanogaster - effects of laboratory culturing and stages in life cycle

    International Nuclear Information System (INIS)

    Radiation induced damages are due to direct effect of radiation energy or through free radical generation. Recent studies suggest Drosophila to be a good animal model to study radiation tolerance. The present study on female Drosophila melanogaster was conducted to observe 1. Variations in larval and adult radiation tolerance 2. Variations in laboratory culture and field populations of Drosophila. Third instar larvae were exposed to gamma radiation of 6, 10, 20, 30, 40 and 50 Gy in gamma chamber GC 5000 (BRT, India). Larvae of flies collected from the field were reared for two generations in the lab before irradiation. The laboratory cultured files were from stocks that were maintained for more than 1000 generations. The larvae of field populations had higher survival rate at 51% as compared to 43% in case of cultured flies and thus more resistant. The III instar larval stage (lab culture) had a LD50 of 26 Gy as compared to LD 50 of 928 Gy in case of adult flies have ∼ 160 times higher tolerance compared to humans. Prolonged rearing comparable to 'domestication' might have induced reduction in tolerance. Larval stages have a lower tolerance than adults possibly due to higher metabolic rate. Adults are post-mitotic in nature with very low rate of cell division. This may contribute to higher tolerance. This however is in contradiction to studies of midge (Chironomous) where larvae also have higher tolerance. (author)

  6. A Prospective Randomized Study of Adjuvant Chemotherapy in Completely Resected Stage Ⅲ-N2 Non Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To evaluate the effect of postoperative adjuvant chemotherapy on survival after complete resection of stage Ⅲ-N2 non-small-cell lung cancer. Methods: From Jan. 1999 to Dec. 2003, one-hundred and fifty patients, who were diagnosed as stage Ⅲ-N2 non-small cell lung cancer after operation, were randomly devided into chemotherapy group and control group. The former received four cycles of chemotherapy with NVB (25 mg/m2,D1, D5)/paclitaxel (175 mg/m2, DI) and Carboplatin (AUC=5, D1). Results: In chemotherapy group, 75.8% (68/79) of patients had finished the 4 cycles of chemotherapy and no one died of toxic effects of chemotherapy.Twenty-five percent of the patients had grade 3-4 neutropenia and 2% had febrile neutropenia. The median survival for the entire 150 patients was 879 d, with 1-year survival rate of 81%, 2-year survival rate of 59% and 3-year survival rate of 43%. There was no significant difference in median survival between chemotherapy and control group (897 d vs 821 d, P=0.0527), but there was significant difference in the 1-year and 2-year overall survival (94.71%, 76.28% vs 512 d, P=0.122), but there was significant difference in the 2-year survival rate between two groups with brain metastases (66.7% vs 37.6% P<0.05). The median survival after brain metastasis appeared was 190 days. Conclusion: Postoperative adjuvant chemotherapy does not significantly improve median survival among patients with completely resected stage Ⅱ-N2 non-small-cell lung cancer, but significantly improves the 1-year and 2-year overall survival. It neither decreases the incidence of brain metastasis but put off the time of brain metastasis.

  7. The effects of phenoxodiol on the cell cycle of prostate cancer cell lines

    OpenAIRE

    Mahoney, Simon; Arfuso, Frank; Millward, Michael; Dharmarajan, Arun

    2014-01-01

    Background Prostate cancer is associated with a poor survival rate. The ability of cancer cells to evade apoptosis and exhibit limitless replication potential allows for progression of cancer from a benign to a metastatic phenotype. The aim of this study was to investigate in vitro the effect of the isoflavone phenoxodiol on the expression of cell cycle genes. Methods Three prostate cancer cell lines-LNCaP, DU145, and PC3 were cultured in vitro, and then treated with phenoxodiol (10 μM and 30...

  8. DNA Damage, Cell Cycle Arrest, and Apoptosis Induction Caused by Lead in Human Leukemia Cells

    OpenAIRE

    Yedjou, Clement G.; Tchounwou, Hervey M.; Tchounwou, Paul B.

    2015-01-01

    In recent years, the industrial use of lead has been significantly reduced from paints and ceramic products, caulking, and pipe solder. Despite this progress, lead exposure continues to be a significant public health concern. The main goal of this research was to determine the in vitro mechanisms of lead nitrate [Pb(NO3)2] to induce DNA damage, apoptosis, and cell cycle arrest in human leukemia (HL-60) cells. To reach our goal, HL-60 cells were treated with different concentrations of Pb(NO3)...

  9. Effects of allitridi on cell cycle arrest of human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Min-Wen Ha; Rui Ma; Li-Ping Shun; Yue-Hua Gong; Yuan Yuan

    2005-01-01

    AIM: To determine the effect of allitridi on cell cycle of human gastric cancer (HGC) cell lines MGC803 and SGC7901 and its possible mechanism.METHODS: Trypan blue dye exclusion was used to evaluate the proliferation, inhibition of cells and damages of these cells were detected with electron microscope.Flow cytometry and cell mitotic index were used to analyze the change of cell cycle, immunohistochemistry, and RT-PCR was used to examine expression of the p21WAF1 gene.RESULTS: MGC803 cell growth was inhibited by allitridi with 24 h IC50 being 6.4 μg/mL. SGC7901 cell growth was also inhibited by allitridi with 24 h IC50 being 7.3 μg/mL.After being treated with allitridi at the concentration of 12 μg/mL for 24 h, cells were found to have direct cytotoxic effects, including broken cellular membrane, swollen and vesiculated mitochondria and rough endoplasmic reticula,and mass lipid droplet. When cells were treated with allitridi at the concentration of 3, 6, and 9 μg/mL for 24 h, the percentage of G0/G1 phase cells was decreased and that of G2/M phase cells was significantly increased (P = 0.002)compared with those in the group. When cells were treated with allitridi at the concentration of 6 μg/mL, cell mitotic index was much higher (P = 0.003) than that of control group, indicating that allitridi could cause gastric cancer cell arrest in M phase. Besides, the expression levels of p21WAF1 gene of MGC803 cells and p21WAF1 gene of SGC7901 cells were remarkably upregulated after treatment.CONCLUSION: Allitridi can cause gastric cancer cell arrest in M phase, and this may be one of the mechanisms for inhibiting cell proliferation. Effect of allitridi on cells in M phas e may be associated with the upregulation of p21WAF1 genes. This study provides experimental data for clinical use of allitridi in the treatment of gastric carcinoma.

  10. Cell cycle arrest biomarkers in human lung cancer cells after treatment with selenium in culture.

    Science.gov (United States)

    Swede, Helen; Dong, Yan; Reid, Mary; Marshall, James; Ip, Clement

    2003-11-01

    In the planning of future intervention trials using chemopreventive agents against lung cancer, it is critical to evaluate the effect on biomarkers implicated specifically in lung carcinogenesis. With the use of the H520 and H522 human lung cancer cell lines, the present study showed that treatment with selenium (in the form of methylseleninic acid) inhibited cell growth, arrested cell cycle progression at G(1), and induced apoptosis as a late event. Because H520 cells were more sensitive to selenium than H522 cells (IC(50) of MSA was 2.5 or 10 micro M for H520 or H522 cells, respectively, at 24 h), a panel of nine cell cycle regulatory proteins known to be involved in G(1)-->S transition was assessed by Western analysis using whole cell lysate from H520 cells. These nine proteins (DP1, cdc25A, cyclin A, cyclin B(1), cyclin D(1), cdk1, cdk5, p21(WAF1), and GADD153) have been reported previously by our laboratory to be modulated by MSA in human breast and prostate cancer cells. Our data showed that only four (DP1, cdc25A, p21(WAF1), and GADD153) of nine biomarkers produced the expected changes after treatment of lung cancer cells with MSA. This finding raises the possibility that the molecular targets sensitive to selenium modulation may be tissue specific. Thus, the selection of selenium biomarkers for evaluation in an intervention trial must be based on empirical data derived from the cancer cell type of interest. PMID:14652289

  11. Effects of hyaluronic acid- chitosan-gelatin complex on the apoptosis and cell cycle of L929 cells

    Institute of Scientific and Technical Information of China (English)

    MAO Jinshu; WANG Xianghui; CUI Yuanlu; YAO Kangde

    2003-01-01

    With the development in the field of tissue engineering, the interaction between biomaterials and cells has been deeply studied. Viewing the cells seeded on the surface of materials as an organic whole, cell cycle and apoptosis are analyzed to deepen the study of cell compatibility on biomaterials, while cellproliferation and differentiation are studied at the same time. In this paper, hyaluronic acid is incorporated into the chitosan-gelatin system. Propidium iodide (PI) was used in cell cycle analysis and the double-staining of cells with annexin-V and PI was applied in cell apoptosis analysis. The results show that incorporated hyaluronic acid shortens the adaptation period of cells on the material surface, and then cells enter the normal cell cycle quickly. In addition, added hyaluronic acid inhibits cell apoptosis triggered by the membranes. Therefore,hyaluronic acid improves the cell compatibility of chitosan-gelatin system and benefits the design of biomimetic materials.

  12. Scrapie affects the maturation cycle and immune complex trapping by follicular dendritic cells in mice.

    Science.gov (United States)

    McGovern, Gillian; Mabbott, Neil; Jeffrey, Martin

    2009-01-01

    Transmissible spongiform encephalopathies (TSEs) or prion diseases are infectious neurological disorders of man and animals, characterised by abnormal disease-associated prion protein (PrP(d)) accumulations in the brain and lymphoreticular system (LRS). Prior to neuroinvasion, TSE agents often accumulate to high levels within the LRS, apparently without affecting immune function. However, our analysis of scrapie-affected sheep shows that PrP(d) accumulations within the LRS are associated with morphological changes to follicular dendritic cells (FDCs) and tingible body macrophages (TBMs). Here we examined FDCs and TBMs in the mesenteric lymph nodes (MLNs) of scrapie-affected mice by light and electron microscopy. In MLNs from uninfected mice, FDCs could be morphologically categorised into immature, mature and regressing forms. However, in scrapie-affected MLNs this maturation cycle was adversely affected. FDCs characteristically trap and retain immune complexes on their surfaces, which they display to B-lymphocytes. In scrapie-affected MLNs, some FDCs were found where areas of normal and abnormal immune complex retention occurred side by side. The latter co-localised with PrP(d) plasmalemmal accumulations. Our data suggest this previously unrecognised morphology represents the initial stage of an abnormal FDC maturation cycle. Alterations to the FDCs included PrP(d) accumulation, abnormal cell membrane ubiquitin and excess immunoglobulin accumulation. Regressing FDCs, in contrast, appeared to lose their membrane-attached PrP(d). Together, these data suggest that TSE infection adversely affects the maturation and regression cycle of FDCs, and that PrP(d) accumulation is causally linked to the abnormal pathology observed. We therefore support the hypothesis that TSEs cause an abnormality in immune function. PMID:19997557

  13. Scrapie affects the maturation cycle and immune complex trapping by follicular dendritic cells in mice.

    Directory of Open Access Journals (Sweden)

    Gillian McGovern

    Full Text Available Transmissible spongiform encephalopathies (TSEs or prion diseases are infectious neurological disorders of man and animals, characterised by abnormal disease-associated prion protein (PrP(d accumulations in the brain and lymphoreticular system (LRS. Prior to neuroinvasion, TSE agents often accumulate to high levels within the LRS, apparently without affecting immune function. However, our analysis of scrapie-affected sheep shows that PrP(d accumulations within the LRS are associated with morphological changes to follicular dendritic cells (FDCs and tingible body macrophages (TBMs. Here we examined FDCs and TBMs in the mesenteric lymph nodes (MLNs of scrapie-affected mice by light and electron microscopy. In MLNs from uninfected mice, FDCs could be morphologically categorised into immature, mature and regressing forms. However, in scrapie-affected MLNs this maturation cycle was adversely affected. FDCs characteristically trap and retain immune complexes on their surfaces, which they display to B-lymphocytes. In scrapie-affected MLNs, some FDCs were found where areas of normal and abnormal immune complex retention occurred side by side. The latter co-localised with PrP(d plasmalemmal accumulations. Our data suggest this previously unrecognised morphology represents the initial stage of an abnormal FDC maturation cycle. Alterations to the FDCs included PrP(d accumulation, abnormal cell membrane ubiquitin and excess immunoglobulin accumulation. Regressing FDCs, in contrast, appeared to lose their membrane-attached PrP(d. Together, these data suggest that TSE infection adversely affects the maturation and regression cycle of FDCs, and that PrP(d accumulation is causally linked to the abnormal pathology observed. We therefore support the hypothesis that TSEs cause an abnormality in immune function.

  14. Pressure, stress, and strain distribution in the double-stage diamond anvil cell

    International Nuclear Information System (INIS)

    Double stage diamond anvil cells (DACs) of two designs have been assembled and tested. We used a standard symmetric DAC with flat or beveled culets as a primary stage and CVD microanvils machined by a focused ion beam as a second. We evaluated pressure, stress, and strain distributions in gold and a mixture of gold and iron as well as in secondary anvils using synchrotron x-ray diffraction with a micro-focused beam. A maximum pressure of 240 GPa was reached independent of the first stage anvil culet size. We found that the stress field generated by the second stage anvils is typical of conventional DAC experiments. The maximum pressures reached are limited by strains developing in the secondary anvil and by cupping of the first stage diamond anvil in the presented experimental designs. Also, our experiments show that pressures of several megabars may be reached without sacrificing the first stage diamond anvils

  15. Pressure, stress, and strain distribution in the double-stage diamond anvil cell

    Energy Technology Data Exchange (ETDEWEB)

    Lobanov, Sergey S., E-mail: slobanov@carnegiescience.edu [Geophysical Laboratory, Carnegie Institution of Washington, Washington, District of Columbia 20015 (United States); V.S. Sobolev Institute of Geology and Mineralogy SB RAS, Novosibirsk 630090 (Russian Federation); Prakapenka, Vitali B.; Prescher, Clemens [Center for Advanced Radiation Sources, University of Chicago, Chicago, Illinois 60632 (United States); Konôpková, Zuzana; Liermann, Hanns-Peter [Photon Science DESY, D-22607 Hamburg (Germany); Crispin, Katherine L. [Geophysical Laboratory, Carnegie Institution of Washington, Washington, District of Columbia 20015 (United States); Zhang, Chi [Key Laboratory of Earth and Planetary Physics, Institute of Geology and Geophysics CAS, Beijing 100029 (China); Goncharov, Alexander F. [Geophysical Laboratory, Carnegie Institution of Washington, Washington, District of Columbia 20015 (United States); Key Laboratory of Materials Physics, Institute of Solid State Physics CAS, Hefei 230031 (China); University of Science and Technology of China, Hefei 230026 (China)

    2015-07-21

    Double stage diamond anvil cells (DACs) of two designs have been assembled and tested. We used a standard symmetric DAC with flat or beveled culets as a primary stage and CVD microanvils machined by a focused ion beam as a second. We evaluated pressure, stress, and strain distributions in gold and a mixture of gold and iron as well as in secondary anvils using synchrotron x-ray diffraction with a micro-focused beam. A maximum pressure of 240 GPa was reached independent of the first stage anvil culet size. We found that the stress field generated by the second stage anvils is typical of conventional DAC experiments. The maximum pressures reached are limited by strains developing in the secondary anvil and by cupping of the first stage diamond anvil in the presented experimental designs. Also, our experiments show that pressures of several megabars may be reached without sacrificing the first stage diamond anvils.

  16. Tea pigments induce cell-cycle arrest and apoptosis in HepG2 cells

    Institute of Scientific and Technical Information of China (English)

    Xu-Dong Jia; Chi Han; Jun-Shi Chen

    2005-01-01

    AIM: To investigate the molecular mechanisms by which tea pigments exert preventive effects on liver carcinogenesis.METHODS: HepG2 cells were seeded at a density of 5×105/well in six-well culture dishes and incubated overnight. The cells then were treated with various concentrations of tea pigments over 3 d, harvested by trypsinization, and counted using a hemocytometer. Flow cytometric analysis was performed by a flow cytometer after propidium iodide labeling. Bcl-2 and p21WAF1 proteins were determined by Western blotting. In addition, DNA laddering assay was performed on treated and untreated cultured HepG2 cells.RESULTS: Tea pigments inhibited the growth of HepG2 cells in a dose-dependent manner. Flow-cytometric analysis showed that tea pigments arrested cell cycle progression at G1 phase. DNA laddering was used to investigate apoptotic cell death, and the result showed that 100 mg/L of tea pigments caused typical DNA laddering. Our study also showed that tea pigments induced upregulation of p21WAF1 protein and downregulation of Bcl-2 protein.CONCLUSION: Tea pigments induce cell-cycle arrest and apoptosis. Tea pigments may be used as an ideal chemopreventive agent.

  17. Stages of Cell Cannibalism--Entosis--in Normal Human Keratinocyte Culture.

    Science.gov (United States)

    Garanina, A S; Khashba, L A; Onishchenko, G E

    2015-11-01

    Entosis is a type of cell cannibalism during which one cell penetrates into another cell and usually dies inside it. Researchers mainly pay attention to initial and final stages of entosis. Besides, tumor cells in suspension are the primary object of studies. In the present study, we investigated morphological changes of both cells-participants of entosis during this process. The substrate-dependent culture of human normal keratinocytes HaCaT was chosen for the work. A combination of light microscopy and scanning electron microscopy was used to prove that one cell was completely surrounded by the plasma membrane of another cell. We investigated such "cell-in-cell" structures and described the structural and functional changes of both cells during entosis. The outer cell nucleus localization and shape were changed. Gradual degradation of the inner cell nucleus and of the junctions between the inner and the outer cells was revealed. Moreover, repeated redistribution of the outer cell membrane organelles (Golgi apparatus, lysosomes, mitochondria, and autophagosomes), rearrangement of its cytoskeleton, and change in the lysosomal, autophagosomal, and mitochondrial state in both entotic cells were observed during entosis. On the basis of these data, we divided entosis into five stages that make it possible to systematize description of this type of cell death. PMID:26615438

  18. A review of findings of a study of rocket based combined cycle engines applied to extensively axisymmetric single stage to orbit vehicles

    Science.gov (United States)

    Foster, Richard W.

    1992-01-01

    Extensively axisymmetric and non-axisymmetric Single Stage To Orbit (SSTO) vehicles are considered. The information is presented in viewgraph form and the following topics are presented: payload comparisons; payload as a percent of dry weight - a system hardware cost indicator; life cycle cost estimations; operations and support costs estimation; selected engine type; and rocket engine specific impulse calculation.

  19. The Earth Science Education Unit's Professional Development Workshop on "The Carbon Question--Cycling, Releasing, Capturing" for Teachers of Key Stages 3 and 4

    Science.gov (United States)

    King, Chris

    2014-01-01

    The revised National Curriculum for Science for key stages 3 and 4 (ages 11-16) in England provides the opportunity to develop a new coherent approach to teaching about the carbon cycle, the use of carbon as a fuel and the resulting issues. The Earth Science Education Unit (ESEU) intends to develop a new workshop to support the teaching of this…

  20. TGEV nucleocapsid protein induces cell cycle arrest and apoptosis through activation of p53 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Li [College of Veterinary Medicine, Northwest A and F University, Yangling, Shaanxi 712100 (China); College of Life Sciences, Hainan Normal University, Haikou, Hainan 571158 (China); Huang, Yong; Du, Qian; Dong, Feng; Zhao, Xiaomin; Zhang, Wenlong; Xu, Xingang [College of Veterinary Medicine, Northwest A and F University, Yangling, Shaanxi 712100 (China); Tong, Dewen, E-mail: dwtong@nwsuaf.edu.cn [College of Veterinary Medicine, Northwest A and F University, Yangling, Shaanxi 712100 (China)

    2014-03-07

    Highlights: • TGEV N protein reduces cell viability by inducing cell cycle arrest and apoptosis. • TGEV N protein induces cell cycle arrest and apoptosis by regulating p53 signaling. • TGEV N protein plays important roles in TGEV-induced cell cycle arrest and apoptosis. - Abstract: Our previous studies showed that TGEV infection could induce cell cycle arrest and apoptosis via activation of p53 signaling in cultured host cells. However, it is unclear which viral gene causes these effects. In this study, we investigated the effects of TGEV nucleocapsid (N) protein on PK-15 cells. We found that TGEV N protein suppressed cell proliferation by causing cell cycle arrest at the S and G2/M phases and apoptosis. Characterization of various cellular proteins that are involved in regulating cell cycle progression demonstrated that the expression of N gene resulted in an accumulation of p53 and p21, which suppressed cyclin B1, cdc2 and cdk2 expression. Moreover, the expression of TGEV N gene promoted translocation of Bax to mitochondria, which in turn caused the release of cytochrome c, followed by activation of caspase-3, resulting in cell apoptosis in the transfected PK-15 cells following cell cycle arrest. Further studies showed that p53 inhibitor attenuated TGEV N protein induced cell cycle arrest at S and G2/M phases and apoptosis through reversing the expression changes of cdc2, cdk2 and cyclin B1 and the translocation changes of Bax and cytochrome c induced by TGEV N protein. Taken together, these results demonstrated that TGEV N protein might play an important role in TGEV infection-induced p53 activation and cell cycle arrest at the S and G2/M phases and apoptosis occurrence.

  1. Arecoline induced cell cycle arrest, apoptosis, and cytotoxicity to human endothelial cells.

    Science.gov (United States)

    Tseng, Shuei-Kuen; Chang, Mei-Chi; Su, Cheng-Yao; Chi, Lin-Yang; Chang, Jenny Zwei-Ching; Tseng, Wan-Yu; Yeung, Sin-Yuet; Hsu, Ming-Lun; Jeng, Jiiang-Huei

    2012-08-01

    Betel quid (BQ) chewing is a common oral habit in South Asia and Taiwan. BQ consumption may increase the risk of oral squamous cell carcinoma (OSCC), oral submucous fibrosis (OSF), and periodontitis as well as systemic diseases (atherosclerosis, hypertension, etc.). However, little is known about the toxic effect of BQ components on endothelial cells that play important roles for angiogenesis, carcinogenesis, tissue fibrosis, and cardiovascular diseases. EAhy 926 (EAHY) endothelial cells were exposed to arecoline, a major BQ alkaloid, for various time periods. Cytotoxicity was estimated by 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay. The cell cycle distribution of EAHY cells residing in sub-G0/G1, G0/G1, S-, and G2/M phases was analyzed by propidium iodide staining of cellular DNA content and flow cytometry. Some EAHY cells retracted, became round-shaped in appearance, and even detached from the culture plate after exposure to higher concentrations of arecoline (> 0.4 mM). At concentrations of 0.4 and 0.8 mM, arecoline induced significant cytotoxicity to EAHY cells. At similar concentrations, arecoline induced G2/M cell cycle arrest and increased sub-G0/G1 population, a hallmark of apoptosis. Interestingly, prolonged exposure to arecoline (0.1 mM) for 12 and 21 days significantly suppressed the proliferation of EAHY cells, whereas EAHY cells showed adaptation and survived when exposed to 0.05 mM arecoline. These results suggest that BQ components may contribute to the pathogenesis of OSF and BQ chewing-related cardiovascular diseases via toxicity to oral or systemic endothelial cells, leading to impairment of vascular function. During BQ chewing, endothelial damage may be induced by areca nut components and associate with the pathogenesis of OSF, periodontitis, and cardiovascular diseases. PMID:21847594

  2. Carrageenan Induces Cell Cycle Arrest in Human Intestinal Epithelial Cells in Vitro1–3

    Science.gov (United States)

    Bhattacharyya, Sumit; Borthakur, Alip; Dudeja, Pradeep K.; Tobacman, Joanne K.

    2016-01-01

    Multiple studies in animal models have shown that the commonly used food additive carrageenan (CGN) induces inflammation and intestinal neoplasia. We performed the first studies to determine the effects of CGN exposure on human intestinal epithelial cells (IEC) in tissue culture and tested the effect of very low concentrations (1–10 mg/L) of undegraded, high-molecular weight CGN. These concentrations of CGN are less than the anticipated exposure of the human colon to CGN from the average Western diet. In the human colonic epithelial cell line NCM460 and in primary human colonic epithelial cells that were exposed to CGN for 1–8 d, we found increased cell death, reduced cell proliferation, and cell cycle arrest compared with unexposed control cells. After 6–8 d of CGN exposure, the percentage of cells reentering G0–G1 significantly decreased and the percentages of cells in S and G2-M phases significantly increased. Increases in activated p53, p21, and p15 followed CGN exposure, consistent with CGN-induced cell cycle arrest. Additional data, including DNA ladder, poly ADP ribose polymerase Western blot, nuclear DNA staining, and activities of caspases 3 and 7, indicated no evidence of increased apoptosis following CGN exposure and were consistent with CGN-induced necrotic cell death. These data document for the first time, to our knowledge, marked adverse effects of low concentrations of CGN on survival of normal human IEC and suggest that CGN exposure may have a role in development of human intestinal pathology. PMID:18287351

  3. Analysis of cell-cycle regulation following exposure of lung-derived cells to γ-rays

    Science.gov (United States)

    Trani, D.; Lucchetti, C.; Cassone, M.; D'Agostino, L.; Caputi, M.; Giordano, A.

    Acute exposure of mammalian cells to ionizing radiation results in a delay of cell-cycle progression and/or augmentation of apoptosis. Following ionizing radiation-induced DNA damage, cell-cycle arrest in the G1- or G2-phase of the cell-cycle prevents or delays DNA replication or mitosis, providing time for the DNA repair machinery to exert its function. Deregulation or failing of cell-cycle checkpoints and/or DNA repair mechanisms may lead normal cells bearing chromosome mutations to acquire neoplastic autonomy, which in turn can trigger the onset of cancer. Existing studies have focused on the impact of p53 status on the radiation response of lung cancer (LC) cell lines in terms of both cell-cycle regulation and apoptosis, while no comparative studies have been performed on the radiation response of lung derived normal and cancerous epithelial cells. To investigate the radiation response in normal and cancerous phenotypes, along with the role and impact of p53 status, and possible correlations with pRb/p105 or other proteins involved in carcinogenesis and cell-cycle regulation, we selected two lung-derived epithelial cell lines, one normal (NL20, p53 wild-type) and one non-small cell lung cancer (NSCLC), H358 (known to be p53-deficient). We compared the levels of γ-induced cell proliferation ability, cell-cycle arrest, apoptotic index, and expression levels of cell-cycle regulating and regulated proteins. The different cell sensitivity, apoptotic response and protein expression profiles resulting from our study for NL20 and H358 cells suggest that still unknown mechanisms involving p53, pRb/p105 and their target molecules might play a pivotal role in determining cell sensitivity and resistance upon exposure to ionizing radiation.

  4. {gamma}-irradiation deregulates cell cycle control and apoptosis in nevoid basal cell carcinomas syndrome-derived cells

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Katsunori; Miyashita, Toshiyuki; Yamada, Masao [National Children' s Medical Research Center, Tokyo (Japan); Takanashi, Jun-ichi; Sugita, Katsuo; Kohno, Yoichi; Nishie, Haruko; Yasumoto, Shin-ichiro; Furue, Masutaka

    1999-12-01

    The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by nevi, palmar and plantar pits, falx calcification, vertebrate anomalies and basal cell carcinomas. It is well known in NBCCS that {gamma}-irradiation to the skin induces basal cell carcinomas or causes an enlargement of the tumor size, although the details of the mechanism remain unknown. We have established lymphoblastoid cell lines from three NBCCS patients, and we present here the first evidence of abnormal cell cycle and apoptosis regulations. A novel mutation (single nucleotide deletion) in the coding region of the human patched gene, PTCH, was identified in two sibling patients, but no apparent abnormalities were detected in the gene of the remaining patient. Nevertheless, the three established cell lines showed similar features in the following analyses. Flow cytometric analyses revealed that the NBCCS-derived cells were accumulated in the G{sub 2}M phase after {gamma}-irradiation, whereas normal cells showed cell cycle arrest both in the G{sub 0}G{sub 1} and G{sub 2}M phases. The fraction of apoptotic cells after {gamma}-irradiation was smaller in the NBCCS cells. The level of p27 expression markedly decreased after {gamma}-irradiation in the NBCCS cells, although the effects of the irradiation on the expression profiles for p53, p21 and Rb did not differ in normal and NBCCS cells. These findings may provide a clue to the molecular mechanisms of tumorigenesis in NBCCS. (author)

  5. Effects of arsenic trioxide and strontium-89 chloride on the cell cycle and apoptosis of human breast cancer cell line MCF-7

    International Nuclear Information System (INIS)

    Objective: To investigate the effects of arsenic trioxide (As2O3) and 89SrCl2 (strontium 89 chloride) co-treatment on the cell cycle and apoptosis of MCF-7 human breast cancer cell line. Methods: The MTT method was applied to explored the impacts of As2O3 on the proliferation of MCF-7 cell, and select the proper concentration of As2O3 to use. The cells were randomly divided into four groups: control group, As2O3 treatment group, 89SrCl2 irradiation group and As2O3 and 89SrCl2 co-treatment group (combining group). The cell cycle distribution and apoptosis were analyzed by flow cytometry at 24 h after treatment. Results: The results showed As2O3 could significantly inhibite the growth of MCF-7 cells and the 24 h ID50 was 11.7μmol/L. The cells during G2/M phase in combining group was significantly more than that in 89SrCl2 irradiation group and the death cells and cells at early stage of apoptosis in combining group predominantly increased, significantly different from that in 89Sr irradiation group (P 2O3could promote G2 arrest apoptosis of the MCF-7 cells induced by exposure to 89SrCl2. (authors)

  6. Antiproliferative effect of rapamycin on human T-cell leukemia cell line Jurkat by cell cycle arrest and telomerase inhibition

    Institute of Scientific and Technical Information of China (English)

    Yan-min ZHAO; Qian ZHOU; Yun XU; Xiao-yu LAI; He HUANG

    2008-01-01

    Aim:To examine the ability of rapamycin to suppress growth and regulate telomerase activity in the human T-cell leukemia cell line Jurkat. Methods:Cell proliferation was assessed after exposure to rapamycin by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were determined by flow cytometry. The proteins important for cell cycle progres-sion and Akt/mammalian target of rapamycin signaling cascade were assessed by Western blotting. Telomerase activity was quantified by telomeric repeat amplication protocol assay. The human telomerase reverse transcriptase (hTERT) mRNA levels were determined by semi-quantitative RT-PCR. Results:Rapamycin inhibited the proliferation of Jurkat, induced G1 phase arrest, unregulated the pro-tein level of p21 as well as p27, and downregulated cyclinD3, phospho-p70s6k, and phospho-s6, but had no effect on apoptosis. Treatment with rapamycin reduced telomerase activity, and reduced hTERT mRNA and protein expression. Conclusion:Rapamycin displayed a potent antileukemic effect in the human T-cell leukemia cell line by inhibition of cell proliferation through G1 cell cycle arrest and also through the suppression of telomerase activity, suggesting that rapamycin may have potential clinical implications in the treatment of some leukemias.

  7. PINCH1 regulates cell-matrix and cell-cell adhesions, cell polarity and cell survival during the peri-implantation stage

    DEFF Research Database (Denmark)

    Li, Shaohua; Bordoy, Randi; Stanchi, Fabio;

    2005-01-01

    integrin or Ilk, loss of PINCH1 arrested development at the peri-implantation stage. In contrast to beta1 integrin or Ilk mutants, however, disruption of the PINCH1 gene produced implantation chambers with visible cell clumps even at embryonic day 9.5. In order to define the phenotype leading to the peri...

  8. Radioprotection and Cell Cycle Arrest of Intestinal Epithelial Cells by Darinaparsin, a Tumor Radiosensitizer

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Junqiang; Doi, Hiroshi [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States); Saar, Matthias; Santos, Jennifer [Department of Urology, School of Medicine, Stanford University, Stanford, California (United States); Li, Xuejun; Peehl, Donna M. [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States); Knox, Susan J., E-mail: sknox@stanford.edu [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States)

    2013-12-01

    Purpose: It was recently reported that the organic arsenic compound darinaparsin (DPS) is a cytotoxin and radiosensitizer of tumor cells in vitro and in subcutaneous xenograft tumors. Surprisingly, it was also found that DPS protects normal intestinal crypt epithelial cells (CECs) from clonogenic death after ionizing radiation (IR). Here we tested the DPS radiosensitizing effect in a clinically relevant model of prostate cancer and explored the radioprotective effect and mechanism of DPS on CECs. Methods and Materials: The radiation modification effect of DPS was tested in a mouse model of orthotopic xenograft prostate cancer and of IR-induced acute gastrointestinal syndrome. The effect of DPS on CEC DNA damage and DNA damage responses was determined by immunohistochemistry. Results: In the mouse model of IR-induced gastrointestinal syndrome, DPS treatment before IR accelerated recovery from body weight loss and increased animal survival. DPS decreased post-IR DNA damage and cell death, suggesting that the radioprotective effect was mediated by enhanced DNA damage repair. Shortly after DPS injection, significant cell cycle arrest was observed in CECs at both G1/S and G2/M checkpoints, which was accompanied by the activation of cell cycle inhibitors p21 and growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A). Further investigation revealed that DPS activated ataxia telangiectasia mutated (ATM), an important inducer of DNA damage repair and cell cycle arrest. Conclusions: DPS selectively radioprotected normal intestinal CECs and sensitized prostate cancer cells in a clinically relevant model. This effect may be, at least in part, mediated by DNA damage response activation and has the potential to significantly increase the therapeutic index of radiation therapy.

  9. Radioprotection and Cell Cycle Arrest of Intestinal Epithelial Cells by Darinaparsin, a Tumor Radiosensitizer

    International Nuclear Information System (INIS)

    Purpose: It was recently reported that the organic arsenic compound darinaparsin (DPS) is a cytotoxin and radiosensitizer of tumor cells in vitro and in subcutaneous xenograft tumors. Surprisingly, it was also found that DPS protects normal intestinal crypt epithelial cells (CECs) from clonogenic death after ionizing radiation (IR). Here we tested the DPS radiosensitizing effect in a clinically relevant model of prostate cancer and explored the radioprotective effect and mechanism of DPS on CECs. Methods and Materials: The radiation modification effect of DPS was tested in a mouse model of orthotopic xenograft prostate cancer and of IR-induced acute gastrointestinal syndrome. The effect of DPS on CEC DNA damage and DNA damage responses was determined by immunohistochemistry. Results: In the mouse model of IR-induced gastrointestinal syndrome, DPS treatment before IR accelerated recovery from body weight loss and increased animal survival. DPS decreased post-IR DNA damage and cell death, suggesting that the radioprotective effect was mediated by enhanced DNA damage repair. Shortly after DPS injection, significant cell cycle arrest was observed in CECs at both G1/S and G2/M checkpoints, which was accompanied by the activation of cell cycle inhibitors p21 and growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A). Further investigation revealed that DPS activated ataxia telangiectasia mutated (ATM), an important inducer of DNA damage repair and cell cycle arrest. Conclusions: DPS selectively radioprotected normal intestinal CECs and sensitized prostate cancer cells in a clinically relevant model. This effect may be, at least in part, mediated by DNA damage response activation and has the potential to significantly increase the therapeutic index of radiation therapy

  10. [The irido-corneo-endothelial syndrome. The loss of the control of corneal endothelial cell cycle. A review].

    Science.gov (United States)

    Robert, A M; Renard, G; Robert, L; Bourges, J-L

    2013-04-01

    The three major symptoms of the irido-corneo-endothelial syndrome are the alterations of the corneal endothelium and of the iris with a loss of the regulation of the cell cycle, and the progressive obstruction of the irido-corneal angle. This rare pathology attacks mainly young adult women. Most of the symptoms and complications originate from the excessive proliferation of the corneal endothelial cells accompanied by the evolution of their phenotype towards that of the epithelial cells. In normal conditions the corneal endothelial cells do not divide, they are blocked in the G1 stage of the cell cycle, mainly because of the action of the inhibitors of cyclin-dependent kinases. Still these cells retain a good capacity for proliferation, which can be induced by the down-regulation of the expression of the inhibitors of the cyclin-dependent kinases. This proliferative capacity declines with age and is also different according to the localization of the cells: it is more intense with those originating from the central area then in those from the peripheral area of the cornea. The age-related decline of the proliferative capacity is not due to the shortening of the telomers, but to the stress-induced accelerated senescence of the cells. PMID:23123109

  11. TRAP1 regulates cell cycle and apoptosis in thyroid carcinoma cells.

    Science.gov (United States)

    Palladino, Giuseppe; Notarangelo, Tiziana; Pannone, Giuseppe; Piscazzi, Annamaria; Lamacchia, Olga; Sisinni, Lorenza; Spagnoletti, Girolamo; Toti, Paolo; Santoro, Angela; Storto, Giovanni; Bufo, Pantaleo; Cignarelli, Mauro; Esposito, Franca; Landriscina, Matteo

    2016-09-01

    Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a heat shock protein 90 (HSP90) molecular chaperone upregulated in several human malignancies and involved in protection from apoptosis and drug resistance, cell cycle progression, cell metabolism and quality control of specific client proteins. TRAP1 role in thyroid carcinoma (TC), still unaddressed at present, was investigated by analyzing its expression in a cohort of 86 human TCs and evaluating its involvement in cancer cell survival and proliferation in vitro Indeed, TRAP1 levels progressively increased from normal peritumoral thyroid gland, to papillary TCs (PTCs), follicular variants of PTCs (FV-PTCs) and poorly differentiated TCs (PDTCs). By contrast, anaplastic thyroid tumors exhibited a dual pattern, the majority being characterized by high TRAP1 levels, while a small subgroup completely negative. Consistently with a potential involvement of TRAP1 in thyroid carcinogenesis, TRAP1 silencing resulted in increased sensitivity to paclitaxel-induced apoptosis, inhibition of cell cycle progression and attenuation of ERK signaling. Noteworthy, the inhibition of TRAP1 ATPase activity by pharmacological agents resulted in attenuation of cell proliferation, inhibition of ERK signaling and reversion of drug resistance. These data suggest that TRAP1 inhibition may be regarded as potential strategy to target specific features of human TCs, i.e., cell proliferation and resistance to apoptosis. PMID:27422900

  12. Osthole inhibits proliferation of human breast cancer cells by inducing cell cycle arrest and apoptosis

    Institute of Scientific and Technical Information of China (English)

    Lintao Wang; Yanyan Peng; Kaikai Shi; Haixiao Wang; Jianlei Lu; Yanli Li; Changyan Ma

    2015-01-01

    Recent studies have revealed that osthole,an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson,a traditional Chinese medicine,possesses anticancer activity.However,its effect on breast cancer cells so far has not been elucidated clearly.In the present study,we evaluated the effects of osthole on the proliferation,cell cycle and apoptosis of human breast cancer cells MDA-MB 435.We demonstrated that osthole is effective in inhibiting the proliferation of MDA-MB 435 cells,The mitochondrion-mediated apoptotic pathway was involved in apoptosis induced by osthole,as indicated by activation of caspase-9 and caspase-3 followed by PARP degradation.The mechanism underlying its effect on the induction of G1 phase arrest was due to the up-regulation of p53 and p21 and down-regulation of Cdk2 and cyclin D1 expression.Were observed taken together,these findings suggest that the anticancer efficacy of osthole is mediated via induction of cell cycle arrest and apoptosis in human breast cancer cells and osthole may be a potential chemotherapeutic agent against human breast cancer.

  13. The steady-state level and stability of TLS polymerase eta are cell cycle dependent in the yeast S. cerevisiae.

    Science.gov (United States)

    Plachta, Michal; Halas, Agnieszka; McIntyre, Justyna; Sledziewska-Gojska, Ewa

    2015-05-01

    Polymerase eta (Pol eta) is a ubiquitous translesion DNA polymerase that is capable of bypassing UV-induced pyrimidine dimers in an error-free manner. However, this specialized polymerase is error prone when synthesizing through an undamaged DNA template. In Saccharomyces cerevisiae, both depletion and overproduction of Pol eta result in mutator phenotypes. Therefore, regulation of the cellular abundance of this enzyme is of particular interest. However, based on the investigation of variously tagged forms of Pol eta, mutually contradictory conclusions have been reached regarding the stability of this polymerase in yeast. Here, we optimized a protocol for the detection of untagged yeast Pol eta and established that the half-life of the native enzyme is 80 ± 14 min in asynchronously growing cultures. Experiments with synchronized cells indicated that the cellular abundance of this translesion polymerase changes throughout the cell cycle. Accordingly, we show that the stability of Pol eta, but not its mRNA level, is cell cycle stage dependent. The half-life of the polymerase is more than fourfold shorter in G1-arrested cells than in those at G2/M. Our results, in concert with previous data for Rev1, indicate that cell cycle regulation is a general property of Y family TLS polymerases in S. cerevisiae. PMID:25766643

  14. Specific requirement of the chromatin modifier mSin3B in cell cycle exit and cellular differentiation.

    Science.gov (United States)

    David, Gregory; Grandinetti, Kathryn B; Finnerty, Patricia M; Simpson, Natalie; Chu, Gerald C; Depinho, Ronald A

    2008-03-18

    The Sin3-histone deacetylase (HDAC) corepressor complex is conserved from yeast to humans. Mammals possess two highly related Sin3 proteins, mSin3A and mSin3B, which serve as scaffolds tethering HDAC enzymatic activity, and numerous sequence-specific transcription factors to enable local chromatin regulation at specific gene targets. Despite broad overlapping expression of mSin3A and mSin3B, mSin3A is cell-essential and vital for early embryonic development. Here, genetic disruption of mSin3B reveals a very different phenotype characterized by the survival of cultured cells and lethality at late stages of embryonic development with defective differentiation of multiple lineages-phenotypes that are strikingly reminiscent of those associated with loss of retinoblastoma family members or E2F transcriptional repressors. Additionally, we observe that, whereas mSin3B(-/-) cells cycle normally under standard growth conditions, they show an impaired ability to exit the cell cycle with limiting growth factors. Correspondingly, mSin3B interacts physically with the promoters of known E2F target genes, and its deficiency is associated with derepression of these gene targets in vivo. Together, these results reveal a critical role for mSin3B in the control of cell cycle exit and terminal differentiation in mammals and establish contrasting roles for the mSin3 proteins in the growth and development of specific lineages. PMID:18332431

  15. Intralimb Coordination Patterns in Absent, Mild, and Severe Stages of Diabetic Neuropathy: Looking Beyond Kinematic Analysis of Gait Cycle.

    Directory of Open Access Journals (Sweden)

    Liu Chiao Yi

    Full Text Available Diabetes Mellitus progressively leads to impairments in stability and joint motion and might affect coordination patterns, mainly due to neuropathy. This study aims to describe changes in intralimb joint coordination in healthy individuals and patients with absent, mild and, severe stages of neuropathy.Forty-seven diabetic patients were classified into three groups of neuropathic severity by a fuzzy model: 18 without neuropathy (DIAB, 7 with mild neuropathy (MILD, and 22 with moderate to severe neuropathy (SVRE. Thirteen healthy subjects were included as controls (CTRL. Continuous relative phase (CRP was calculated at each instant of the gait cycle for each pair of lower limb joints. Analysis of Variance compared each frame of the CRP time series and its standard deviation among groups (α = 5%.For the ankle-hip CRP, the SVRE group presented increased variability at the propulsion phase and a distinct pattern at the propulsion and initial swing phases compared to the DIAB and CTRL groups. For the ankle-knee CRP, the 3 diabetic groups presented more anti-phase ratios than the CTRL group at the midstance, propulsion, and terminal swing phases, with decreased variability at the early stance phase. For the knee-hip CRP, the MILD group showed more in-phase ratio at the early stance and terminal swing phases and lower variability compared to all other groups. All diabetic groups were more in-phase at early the midstance phase (with lower variability than the control group.The low variability and coordination differences of the MILD group showed that gait coordination might be altered not only when frank evidence of neuropathy is present, but also when neuropathy is still incipient. The ankle-knee CRP at the initial swing phase showed distinct patterns for groups from all degrees of neuropathic severity and CTRLs. The ankle-hip CRP pattern distinguished the SVRE patients from other diabetic groups, particularly in the transitional phase from stance to

  16. A Two-stage DC-DC Converter for the Fuel Cell-Supercapacitor Hybrid System

    DEFF Research Database (Denmark)

    Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael A. E.

    2009-01-01

    A wide input range multi-stage converter is proposed with the fuel cells and supercapacitors as a hybrid system. The front-end two-phase boost converter is used to optimize the output power and to reduce the current ripple of fuel cells. The supercapacitor power module is connected by push......-pull-forward half bridge (PPFHB) converter with coupled inductors in the second stage to handle the slow transient response of the fuel cells and realize the bidirectional power flow control. Moreover, this cascaded structure simplifies the power management. The control strategy for the whole system is analyzed and...

  17. A Two-stage DC-DC Converter for the Fuel Cell-Supercapacitor Hybrid System

    OpenAIRE

    Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael A. E.

    2009-01-01

    A wide input range multi-stage converter is proposed with the fuel cells and supercapacitors as a hybrid system. The front-end two-phase boost converter is used to optimize the output power and to reduce the current ripple of fuel cells. The supercapacitor power module is connected by push-pull-forward half bridge (PPFHB) converter with coupled inductors in the second stage to handle the slow transient response of the fuel cells and realize the bidirectional power flow control. Moreover, this...

  18. The role of the cell cycle machinery in resumption of postembryonic development

    NARCIS (Netherlands)

    Barroco, R.M.; Poucke, van K.; Bergervoet, J.H.W.; Veylder, de L.; Groot, S.P.C.; Inze, D.; Engler, G.

    2005-01-01

    Cell cycle activity is required for plant growth and development, but its involvement in the early events that initiate seedling development remains to be clarified. We performed experiments aimed at understanding when cell cycle progression is activated during seed germination, and what its contrib

  19. RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Houcai; Yu, Jing; Zhang, Lixia; Xiong, Yuanyuan; Chen, Shuying; Xing, Haiyan; Tian, Zheng; Tang, Kejing; Wei, Hui; Rao, Qing; Wang, Min; Wang, Jianxiang, E-mail: wangjx@ihcams.ac.cn

    2014-04-18

    Highlights: • RPS27a expression was up-regulated in advanced-phase CML and AL patients. • RPS27a knockdown changed biological property of K562 and K562/G01 cells. • RPS27a knockdown affected Raf/MEK/ERK, P21 and BCL-2 signaling pathways. • RPS27a knockdown may be applicable for new combination therapy in CML patients. - Abstract: Ribosomal protein S27a (RPS27a) could perform extra-ribosomal functions besides imparting a role in ribosome biogenesis and post-translational modifications of proteins. The high expression level of RPS27a was reported in solid tumors, and we found that the expression level of RPS27a was up-regulated in advanced-phase chronic myeloid leukemia (CML) and acute leukemia (AL) patients. In this study, we explored the function of RPS27a in leukemia cells by using CML cell line K562 cells and its imatinib resistant cell line K562/G01 cells. It was observed that the expression level of RPS27a was high in K562 cells and even higher in K562/G01 cells. Further analysis revealed that RPS27a knockdown by shRNA in both K562 and K562G01 cells inhibited the cell viability, induced cell cycle arrest at S and G2/M phases and increased cell apoptosis induced by imatinib. Combination of shRNA with imatinib treatment could lead to more cleaved PARP and cleaved caspase-3 expression in RPS27a knockdown cells. Further, it was found that phospho-ERK(p-ERK) and BCL-2 were down-regulated and P21 up-regulated in RPS27a knockdown cells. In conclusion, RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells. It appears that drugs targeting RPS27a combining with tyrosine kinase inhibitor (TKI) might represent a novel therapy strategy in TKI resistant CML patients.

  20. A novel parameter, cell-cycle progression index, for radiation dose absorbed estimation in the premature chromosome condensation assay

    International Nuclear Information System (INIS)

    The calyculin A-induced premature chromosome condensation (PCC) assay is a simple and useful method for assessing the cell-cycle distribution in cells, since calyculin A induces chromosome condensation in various phases of the cell cycle. In this study, a novel parameter, the cell-cycle progression index (CPI), in the PCC assay was validated as a novel bio-marker for bio-dosimetry. Peripheral blood was drawn from healthy donors after informed consent was obtained. CPI was investigated using a human peripheral blood lymphocyte (PBL) ex vivo irradiation (60Co-gamma rays: ∼0.6 Gy min-1, or X ray: 1.0 Gy min-1; 0-10 Gy) model. The calyculin A-induced PCC assay was performed for chromosome preparation. PCC cells were divided into the following five categories according to cell-cycle stage: non-PCC, G1-PCC, S-PCC, G2/M-PCC and M/A-PCC cells. CPI was calculated as the ratio of G2/M-PCC cells to G1-PCC cells. The PCC-stage distribution varied markedly with irradiation doses. The G1-PCC cell fraction was significantly reduced, and the G2/M-PCC cell fraction increased, in 10-Gy-irradiated PBL after 48 h of culture. CPI levels were fitted to an exponential dose-response curve with gamma-ray irradiation [y = 0.6729 + 0.3934 exp(0.5685D), r = 1.0000, p < 0.0001] and X-ray irradiation [y = -0.3743 + 0.9744 exp(0.3321D), r = 0.9999, p < 0.0001]. There were no significant individual (p = 0.853) or gender effects (p = 0.951) on the CPI in the human peripheral blood ex vivo irradiation model. Furthermore, CPI measurements are rapid (< 15 min per case). These results suggest that the CPI is a useful screening tool for the assessment of radiation doses received ranging from 0 to 10 Gy in radiation exposure early after a radiation event, especially after a mass-casualty radiological incident. (authors)