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Sample records for alt immortalization reveals

  1. A gene expression signature classifying telomerase and ALT immortalization reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT

    DEFF Research Database (Denmark)

    Lafferty-Whyte, K; Cairney, C J; Will, M B;

    2009-01-01

    Telomere length is maintained by two known mechanisms, the activation of telomerase or alternative lengthening of telomeres (ALT). The molecular mechanisms regulating the ALT phenotype are poorly understood and it is unknown how the decision of which pathway to activate is made at the cellular le...

  2. Interchromosomal Homology Searches Drive Directional ALT Telomere Movement and Synapsis

    OpenAIRE

    Cho, Nam Woo; Dilley, Robert L.; Lampson, Michael A.; Greenberg, Roger A.

    2014-01-01

    Telomere length maintenance is a requisite feature of cellular immortalization and a hallmark of human cancer. While most human cancers express telomerase activity, approximately 10-15% employ a recombination-dependent telomere maintenance pathway known as Alternative Lengthening of Telomeres (ALT) that is characterized by multi-telomere clusters and associated promyelocytic leukemia protein bodies. Here, we show that a DNA double-strand break (DSB) response at ALT telomeres triggers long-ran...

  3. Immortality of cancers

    OpenAIRE

    Duesberg, Peter; McCormack, Amanda

    2013-01-01

    Immortality is a common characteristic of cancers, but its origin and purpose are still unclear. Here we advance a karyotypic theory of immortality based on the theory that carcinogenesis is a form of speciation. Accordingly, cancers are generated from normal cells by random karyotypic rearrangements and selection for cancer-specific reproductive autonomy. Since such rearrangements unbalance long-established mitosis genes, cancer karyotypes vary spontaneously but are stabilized perpetually by...

  4. HPV-16 E7 reveals a link between DNA replication stress, FANCD2 and alternative lengthening of telomeres (ALT)-associated PML bodies (APBs)

    OpenAIRE

    Spardy, Nicole; Duensing, Anette; Hoskins, Elizabeth E.; Wells, Susanne I.; Duensing, Stefan

    2008-01-01

    Expression of the high-risk human papillomavirus (HPV-16) E7 oncoprotein extends the life span of primary human keratinocytes and partially restores telomere length in the absence of telomerase. The molecular basis of this activity is incompletely understood. Here, we show that HPV-16 E7 induces an increased formation of alternative lengthening of telomeres (ALT)-associated PML bodies (APBs) in early passage primary human keratinocytes as well as HPV-negative tumor cells. This activity was fo...

  5. Zeno's Paradox of Immortality.

    Science.gov (United States)

    Olshansky, S Jay; Carnes, Bruce A

    2013-01-01

    Scientists who speculate on the future of human longevity have a broad range of views ranging from the promise of immortality, to radical life extension, to declines in life expectancy. Among those who contend that radical life extension is already here, or on the horizon, or immortality is forthcoming, elements of their reasoning appear surprisingly close, if not identical, to a famous mathematical paradox posed by the ancient Greek mathematician known as Zeno. Here we examine the underlying assumptions behind the views that much longer life expectancies are forthcoming or have already arrived, and place their line of reasoning within the context of a new Zeno paradox described here as The Paradox of Immortality. PMID:22906806

  6. Considerable Life Extension versus Immortality

    OpenAIRE

    Rosa Rantanen

    2012-01-01

    The ethical desirability of considerable life extension by medical technology has become an increasingly discussed topic in bioethics during recent years. Immortality can be seen as a maximum of life extension. Because of this, many authors use the term 'immortality' for referring to a lifespan that is considerably longer than our current one. However, being literally immortal would be very different from living for hundreds, or even thousands, of years. The arguments that have been made abou...

  7. The Immortal Fire Within

    Science.gov (United States)

    Sheehan, William

    2007-12-01

    Preface; Key to abbreviations in notes; 1. Through rugged ways; 2. Ardent and faithful work with a telescope; 3. Mars; his moons and his heavens; 4. A seeker of comets; 5. Vanderbilt astronomer; 6. In the realm of the nebulae; 7. Go west, young man!; 8. Hanging fire; 9. On Mt. Hamilton; 10. A year of wonders; 11. The young rebel; 12. 'I am tired here'; 13. Immortality; 14. Travels and travails; 15. Barnard and Mars; 16. Nature's true artisan; 17. A tide in his affairs; 18. Yerkes observatory; 19. Disappointments and triumphs; 20. The comet and Milky Way photographs; 21. Comet tales; 22. Observer of all that shines - or obscures; 23. Eclipse and decline; 24. Ad astra; Index.

  8. The Role of ATRX in the Alternative Lengthening of Telomeres (ALT Phenotype

    Directory of Open Access Journals (Sweden)

    João P. Amorim

    2016-09-01

    Full Text Available Telomeres are responsible for protecting chromosome ends in order to prevent the loss of coding DNA. Their maintenance is required for achieving immortality by neoplastic cells and can occur by upregulation of the telomerase enzyme or through a homologous recombination-associated process, the alternative lengthening of telomeres (ALT. The precise mechanisms that govern the activation of ALT or telomerase in tumor cells are not fully understood, although cellular origin may favor one of the other mechanisms that have been found thus far in mutual exclusivity. Specific mutational events influence ALT activation and maintenance: a unifying frequent feature of tumors that acquire this phenotype are the recurrent mutations of the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX or Death-Domain Associated Protein (DAXX genes. This review summarizes the established criteria about this phenotype: its prevalence, theoretical molecular mechanisms and relation with ATRX, DAXX and other proteins (directly or indirectly interacting and resulting in the ALT phenotype.

  9. The Role of ATRX in the Alternative Lengthening of Telomeres (ALT) Phenotype.

    Science.gov (United States)

    Amorim, João P; Santos, Gustavo; Vinagre, João; Soares, Paula

    2016-01-01

    Telomeres are responsible for protecting chromosome ends in order to prevent the loss of coding DNA. Their maintenance is required for achieving immortality by neoplastic cells and can occur by upregulation of the telomerase enzyme or through a homologous recombination-associated process, the alternative lengthening of telomeres (ALT). The precise mechanisms that govern the activation of ALT or telomerase in tumor cells are not fully understood, although cellular origin may favor one of the other mechanisms that have been found thus far in mutual exclusivity. Specific mutational events influence ALT activation and maintenance: a unifying frequent feature of tumors that acquire this phenotype are the recurrent mutations of the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) or Death-Domain Associated Protein (DAXX) genes. This review summarizes the established criteria about this phenotype: its prevalence, theoretical molecular mechanisms and relation with ATRX, DAXX and other proteins (directly or indirectly interacting and resulting in the ALT phenotype). PMID:27657132

  10. The Role of ATRX in the Alternative Lengthening of Telomeres (ALT) Phenotype

    Science.gov (United States)

    Amorim, João P.; Santos, Gustavo; Vinagre, João; Soares, Paula

    2016-01-01

    Telomeres are responsible for protecting chromosome ends in order to prevent the loss of coding DNA. Their maintenance is required for achieving immortality by neoplastic cells and can occur by upregulation of the telomerase enzyme or through a homologous recombination-associated process, the alternative lengthening of telomeres (ALT). The precise mechanisms that govern the activation of ALT or telomerase in tumor cells are not fully understood, although cellular origin may favor one of the other mechanisms that have been found thus far in mutual exclusivity. Specific mutational events influence ALT activation and maintenance: a unifying frequent feature of tumors that acquire this phenotype are the recurrent mutations of the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) or Death-Domain Associated Protein (DAXX) genes. This review summarizes the established criteria about this phenotype: its prevalence, theoretical molecular mechanisms and relation with ATRX, DAXX and other proteins (directly or indirectly interacting and resulting in the ALT phenotype). PMID:27657132

  11. A role for monoubiquitinated FANCD2 at telomeres in ALT cells

    OpenAIRE

    Fan, Qiang; Zhang, Fan; Barrett, Briana; Ren, Keqin; Andreassen, Paul R.

    2009-01-01

    Both Fanconi anemia (FA) and telomere dysfunction are associated with chromosome instability and an increased risk of cancer. Because of these similarities, we have investigated whether there is a relationship between the FA protein, FANCD2 and telomeres. We find that FANCD2 nuclear foci colocalize with telomeres and PML bodies in immortalized telomerase-negative cells. These cells maintain telomeres by alternative lengthening of telomeres (ALT). In contrast, FANCD2 does not colocalize with t...

  12. ALT Telomeres borrow from meiosis

    OpenAIRE

    Arnoult, Nausica; Karlseder, Jan

    2014-01-01

    The clustering of telomeres is required for the homologous recombination events that maintain chromosome ends in cells relying on alternative lengthening of telomeres (ALT). New data emerged to demonstrate that damage signaling at telomeres induces directional movement and synapsis, driven by the machinery responsible for recombination in meiosis.

  13. Toivo Alt : "Sild tuleb." / Toivo Alt ; interv. Taavi Raudne

    Index Scriptorium Estoniae

    Alt, Toivo, 1957-

    2004-01-01

    Toivo Alt räägib intervjuus marjafirma Saarek tegevusest, Linnuse Kalja kaubamärgi ja Ösel Foods'i aktsiate müügist, erimeelsuste põhjustest endise äripartneri Vjatsheslav Leedoga ning äriideest ehitada mandri ja Muhumaa vahele 2010. aastaks sild. Vt. samas: Kohe näha, et vanad sõbrad; Leedo arvamus

  14. Immortality of Cu damascene interconnects

    Science.gov (United States)

    Hau-Riege, Stefan P.

    2002-04-01

    We have studied short-line effects in fully-integrated Cu damascene interconnects through electromigration experiments on lines of various lengths and embedded in different dielectric materials. We compare these results with results from analogous experiments on subtractively-etched Al-based interconnects. It is known that Al-based interconnects exhibit three different behaviors, depending on the magnitude of the product of current density, j, and line length, L: For small values of (jL), no void nucleation occurs, and the line is immortal. For intermediate values, voids nucleate, but the line does not fail because the current can flow through the higher-resistivity refractory-metal-based shunt layers. Here, the resistance of the line increases but eventually saturates, and the relative resistance increase is proportional to (jL/B), where B is the effective elastic modulus of the metallization system. For large values of (jL/B), voiding leads to an unacceptably high resistance increase, and the line is considered failed. By contrast, we observed only two regimes for Cu-based interconnects: Either the resistance of the line stays constant during the duration of the experiment, and the line is considered immortal, or the line fails due to an abrupt open-circuit failure. The absence of an intermediate regime in which the resistance saturates is due to the absence of a shunt layer that is able to support a large amount of current once voiding occurs. Since voids nucleate much more easily in Cu- than in Al-based interconnects, a small fraction of short Cu lines fails even at low current densities. It is therefore more appropriate to consider the probability of immortality in the case of Cu rather than assuming a sharp boundary between mortality and immortality. The probability of immortality decreases with increasing amount of material depleted from the cathode, which is proportional to (jL2/B) at steady state. By contrast, the immortality of Al-based interconnects is

  15. Disruptive chemicals, senescence and immortality.

    Science.gov (United States)

    Carnero, Amancio; Blanco-Aparicio, Carmen; Kondoh, Hiroshi; Lleonart, Matilde E; Martinez-Leal, Juan Fernando; Mondello, Chiara; Scovassi, A Ivana; Bisson, William H; Amedei, Amedeo; Roy, Rabindra; Woodrick, Jordan; Colacci, Annamaria; Vaccari, Monica; Raju, Jayadev; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Salem, Hosni K; Memeo, Lorenzo; Forte, Stefano; Singh, Neetu; Hamid, Roslida A; Ryan, Elizabeth P; Brown, Dustin G; Wise, John Pierce; Wise, Sandra S; Yasaei, Hemad

    2015-06-01

    Carcinogenesis is thought to be a multistep process, with clonal evolution playing a central role in the process. Clonal evolution involves the repeated 'selection and succession' of rare variant cells that acquire a growth advantage over the remaining cell population through the acquisition of 'driver mutations' enabling a selective advantage in a particular micro-environment. Clonal selection is the driving force behind tumorigenesis and possesses three basic requirements: (i) effective competitive proliferation of the variant clone when compared with its neighboring cells, (ii) acquisition of an indefinite capacity for self-renewal, and (iii) establishment of sufficiently high levels of genetic and epigenetic variability to permit the emergence of rare variants. However, several questions regarding the process of clonal evolution remain. Which cellular processes initiate carcinogenesis in the first place? To what extent are environmental carcinogens responsible for the initiation of clonal evolution? What are the roles of genotoxic and non-genotoxic carcinogens in carcinogenesis? What are the underlying mechanisms responsible for chemical carcinogen-induced cellular immortality? Here, we explore the possible mechanisms of cellular immortalization, the contribution of immortalization to tumorigenesis and the mechanisms by which chemical carcinogens may contribute to these processes. PMID:26106138

  16. Association of BLM and BRCA1 during Telomere Maintenance in ALT Cells.

    Directory of Open Access Journals (Sweden)

    Samir Acharya

    Full Text Available Fifteen percent of tumors utilize recombination-based alternative lengthening of telomeres (ALT to maintain telomeres. The mechanisms underlying ALT are unclear but involve several proteins involved in homologous recombination including the BLM helicase, mutated in Bloom's syndrome, and the BRCA1 tumor suppressor. Cells deficient in either BLM or BRCA1 have phenotypes consistent with telomere dysfunction. Although BLM associates with numerous DNA damage repair proteins including BRCA1 during DNA repair, the functional consequences of BLM-BRCA1 association in telomere maintenance are not completely understood. Our earlier work showed the involvement of BRCA1 in different mechanisms of ALT, and telomere shortening upon loss of BLM in ALT cells. In order to delineate their roles in telomere maintenance, we studied their association in telomere metabolism in cells using ALT. This work shows that BLM and BRCA1 co-localize with RAD50 at telomeres during S- and G2-phases of the cell cycle in immortalized human cells using ALT but not in cells using telomerase to maintain telomeres. Co-immunoprecipitation of BRCA1 and BLM is enhanced in ALT cells at G2. Furthermore, BRCA1 and BLM interact with RAD50 predominantly in S- and G2-phases, respectively. Biochemical assays demonstrate that full-length BRCA1 increases the unwinding rate of BLM three-fold in assays using a DNA substrate that models a forked structure composed of telomeric repeats. Our results suggest that BRCA1 participates in ALT through its interactions with RAD50 and BLM.

  17. L'alt rendiment esporitu

    OpenAIRE

    Escoda, Josep

    2002-01-01

    Josep Escoda observa l’impacte dels Jocs Olímpics en les competicions d’alt rendiment i com aquest ha evolucionat en aquest període de 10 anys. Josep Escoda observa el impacto de los Juegos Olímpicos en las competiciones de alto rendimiento Deportivo y cómo ha evolucionado en éste período de 10 años. Josep Escoda gives an account of the impact of the Olympic Games on high performance competition and how it has evolved over a 10-year period.

  18. SRI AUROBINDO'S CONCEPT OF IMMORTALITY IN SAVITRI

    OpenAIRE

    Londhe N. N.

    2014-01-01

    Sri Aurobindo's Savitri is one of the most philosophical poems in the world literature. Several philosophical and spiritual issues are dealt with a master hand by Sri Aurobindo. Though the concept of immortality is highly debatable, he had a clear idea of the nature of immortality man can attain. He had a very high ideal of immortality of the nature directly derived from the Vedas and Upanishads.

  19. Periodicity and Immortality in Reversible Computing

    OpenAIRE

    Kari, Jarkko; Ollinger, Nicolas

    2008-01-01

    Additional material available on the web at http://www.lif.univ-mrs.fr/~nollinge/rec/gnirut/ We investigate the decidability of the periodicity and the immortality problems in three models of reversible computation: reversible counter machines, reversible Turing machines and reversible one-dimensional cellular automata. Immortality and periodicity are properties that describe the behavior of the model starting from arbitrary initial configurations: immortality is the property of having at ...

  20. Does 'Immortal DNA strand' exist in 'immortal' stem cells?

    Institute of Scientific and Technical Information of China (English)

    Linheng Li

    2007-01-01

    @@ Stem cells function to generate differentiated cells,and,at the same time,are maintained as‘immortal'cells through self-renewal.Accumulated evidence indicates that adult stem cells may be the most common precursor for cancers in adult mammalian tissue[1],and this concept is gaining increasing support[2,3].Meanwhile,this also raises the question of how stem cells,which have a much longer lifespan compared to other progenitor and mature ceils,can avoid accumulating mutations from DNA replica-tion errors.

  1. Immortal solution of the Ricci flow

    Institute of Scientific and Technical Information of China (English)

    RUAN Qihua; CHEN Zhihua

    2005-01-01

    For any complete noncompact Kahler manifold with nonnegative and bounded holomorphic bisectional curvature, we provide the necessary and sufficient condition for the immortal solution to the Ricci flow.

  2. Universal mortality law and immortality

    Science.gov (United States)

    Azbel', Mark Ya.

    2004-10-01

    Well-protected human and laboratory animal populations with abundant resources are evolutionarily unprecedented. Physical approach, which takes advantage of their extensively quantified mortality, establishes that its dominant fraction yields the exact law, which is universal for all animals from yeast to humans. Singularities of the law demonstrate new kinds of stepwise adaptation. The law proves that universal mortality is an evolutionary by-product, which at any given age is reversible, independent of previous life history, and disposable. Life expectancy may be extended, arguably to immortality, by minor biological amendments in the animals. Indeed, in nematodes with a small number of perturbed genes and tissues it increased 6-fold (to 430 years in human terms), with no apparent loss in health and vitality. The law relates universal mortality to specific processes in cells and their genetic regulation.

  3. ALT telomeres get together with nuclear receptors.

    Science.gov (United States)

    Aeby, Eric; Lingner, Joachim

    2015-02-26

    Nuclear receptors bind chromosome ends in "alternative lengthening of telomeres" (ALT) cancer cells that maintain their ends by homologous recombination instead of telomerase. Marzec et al. now demonstrate that, in ALT cells, nuclear receptors not only trigger distal chromatin associations to mediate telomere-telomere recombination events, but also drive chromosome-internal targeted telomere insertions (TTI). PMID:25723159

  4. The catalytic and the RNA subunits of human telomerase are required to immortalize equid primary fibroblasts.

    Science.gov (United States)

    Vidale, Pamela; Magnani, Elisa; Nergadze, Solomon G; Santagostino, Marco; Cristofari, Gael; Smirnova, Alexandra; Mondello, Chiara; Giulotto, Elena

    2012-10-01

    Many human primary somatic cells can be immortalized by inducing telomerase activity through the exogenous expression of the human telomerase catalytic subunit (hTERT). This approach has been extended to the immortalization of cell lines from several mammals. Here, we show that hTERT expression is not sufficient to immortalize primary fibroblasts from three equid species, namely donkey, Burchelli's zebra and Grevy's zebra. In vitro analysis of a reconstituted telomerase composed by hTERT and an equid RNA component of telomerase (TERC) revealed a low activity of this enzyme compared to human telomerase, suggesting a low compatibility of equid and human telomerase subunits. This conclusion was also strengthened by comparison of human and equid TERC sequences, which revealed nucleotide differences in key regions for TERC and TERT interaction. We then succeeded in immortalizing equid fibroblasts by expressing hTERT and hTERC concomitantly. Expression of both human telomerase subunits led to telomerase activity and telomere elongation, indicating that human telomerase is compatible with the other equid telomerase subunits and proteins involved in telomere metabolism. The immortalization procedure described herein could be extended to primary cells from other mammals. The availability of immortal cells from endangered species could be particularly useful for obtaining new information on the organization and function of their genomes, which is relevant for their preservation.

  5. Establishment of immortal normal and ataxia telangiectasia fibroblast cell lines by introduction of the hTERT gene

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Hideaki; Fukami, Hiroko; Hayashi, Yuko; Kiyono, Tohru; Ishizaki, Kanji [Aichi Cancer Center, Nagoya (Japan). Research Inst.; Nakatsugawa, Shigekazu; Hamaguchi, Michinari [Nagoya Univ. (Japan). School of Medicine

    2002-06-01

    To establish immortal human cells, we introduced the human catalytic subunit of telomerase (hTERT) gene into skin fibroblast cells obtained from normal and ataxia telangiectasia (AT) individuals of Japanese origin. After hTERT introduction, these cells continue to grow beyond a population doubling number of 200 while maintaining their original radiosensitivity. Inductions of p53, phosphorylation of Serl5 in p53, and induction of p21 by X-ray irradiation in immortal cells derived from normal individual were not affected by the hTERT introduction. Both normal and AT immortal cells exhibited an apparent inhibition of growth as original primary cells when they reached confluence. Karyotype analysis has revealed that they are in a diploid range. These results suggest that cells immortalized by hTERT introduction retain their original characteristics except for immortalization, and that they may be useful for analyzing various effects of radiation on human cells. (author)

  6. "Tuck Everlasting": Winnie Foster's Intimations of Immortality.

    Science.gov (United States)

    Berger, Peter N.

    1998-01-01

    Tells the plot of the novel "Tuck Everlasting" by Natalie Babbitt--the Tucks are invulnerable and immortal, but everlasting life holds trials for them. Provides seven questions for stimulating student response to the novel. (PA)

  7. Nietzsche, immortality, singularity and eternal recurrence

    OpenAIRE

    Olivier, Bert

    2007-01-01

    Joan Copjec has shown that modernity is privy to a notion of immortality all its own – one that differs fundamentally from any counterpart entertained in Greek antiquity or the Christian Middle Ages. She points to Blumenberg and Lefort as thinkers who have construed this concept in its modern guise in different ways, and ultimately opts for Lefort's paradoxical understanding of immortality as the ‘transcending of time, within time’ before elaborating on a corresponding notion in Lacan's wo...

  8. Differentiation of immortal cells inhibits telomerase activity.

    OpenAIRE

    Sharma, H W; Sokoloski, J A; Perez, J.R.; Maltese, J Y; Sartorelli, A C; Stein, C A; Nichols, G; Khaled, Z.; Telang, N T; Narayanan, R.

    1995-01-01

    Telomerase, a ribonucleic acid-protein complex, adds hexameric repeats of 5'-TTAGGG-3' to the ends of mammalian chromosomal DNA (telomeres) to compensate for the progressive loss that occurs with successive rounds of DNA replication. Although somatic cells do not express telomerase, germ cells and immortalized cells, including neoplastic cells, express this activity. To determine whether the phenotypic differentiation of immortalized cells is linked to the regulation of telomerase activity, t...

  9. Els mites en les altes capacitats

    OpenAIRE

    Gotarda Rodríguez, María del Mar

    2013-01-01

    Davant la diversitat de teories que acompanyen les altes capacitats, la intel·ligència,la sobredotació, el talent, etc., a continuació es presenta el treball que he desenvolupat en el centre privat Sales Jové S.L.P. de Lleida, enfocat a detectar i avaluar infants i adolescents amb altes capacitats. Gràcies a les dades obtingudes he pogut verificar o rebutjar alguns dels mites, creences i tòpics existents sobre les altes capacitats. Ante la diversidad de teorías que acompañan a las altas ca...

  10. Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Gokhan Yildiz

    Full Text Available Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal" by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15

  11. Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.

    Science.gov (United States)

    Yildiz, Gokhan; Arslan-Ergul, Ayca; Bagislar, Sevgi; Konu, Ozlen; Yuzugullu, Haluk; Gursoy-Yuzugullu, Ozge; Ozturk, Nuri; Ozen, Cigdem; Ozdag, Hilal; Erdal, Esra; Karademir, Sedat; Sagol, Ozgul; Mizrak, Dilsa; Bozkaya, Hakan; Ilk, Hakki Gokhan; Ilk, Ozlem; Bilen, Biter; Cetin-Atalay, Rengul; Akar, Nejat; Ozturk, Mehmet

    2013-01-01

    Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal") by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC) development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15-gene

  12. Therapeutic targeting of replicative immortality.

    Science.gov (United States)

    Yaswen, Paul; MacKenzie, Karen L; Keith, W Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-12-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. PMID:25869441

  13. Production of the Allergenic Protein Alt a 1 by Alternaria Isolates from Working Environments

    Directory of Open Access Journals (Sweden)

    Justyna Skóra

    2015-02-01

    Full Text Available The aim of the study was to evaluate the ability of Alternaria isolates from workplaces to produce Alt a 1 allergenic protein, and to analyze whether technical materials (cellulose, compost, leather present within the working environment stimulate or inhibit Alt a 1 production (ELISA test. Studies included identification of the isolated molds by nucleotide sequences analyzing of the ITS1/ITS2 regions, actin, calmodulin and Alt a 1 genes. It has been shown that Alternaria molds are significant part of microbiocenosis in the archive, museum, library, composting plant and tannery (14%–16% frequency in the air. The presence of the gene encoding the Alt a 1 protein has been detected for the strains: Alternaria alternata, A. lini, A. limoniasperae A. nobilis and A. tenuissima. Environmental strains produced Alt a 1 at higher concentrations (1.103–6.528 ng/mL than a ATCC strain (0.551–0.975 ng/mL. It has been shown that the homogenization of the mycelium and the use of ultrafiltration allow a considerable increase of Alt a 1 concentration. Variations in the production of Alt a 1 protein, depend on the strain and extraction methods. These studies revealed no impact of the technical material from the workplaces on the production of Alt a 1 protein.

  14. Production of the allergenic protein Alt a 1 by Alternaria isolates from working environments.

    Science.gov (United States)

    Skóra, Justyna; Otlewska, Anna; Gutarowska, Beata; Leszczyńska, Joanna; Majak, Iwona; Stępień, Łukasz

    2015-02-01

    The aim of the study was to evaluate the ability of Alternaria isolates from workplaces to produce Alt a 1 allergenic protein, and to analyze whether technical materials (cellulose, compost, leather) present within the working environment stimulate or inhibit Alt a 1 production (ELISA test). Studies included identification of the isolated molds by nucleotide sequences analyzing of the ITS1/ITS2 regions, actin, calmodulin and Alt a 1 genes. It has been shown that Alternaria molds are significant part of microbiocenosis in the archive, museum, library, composting plant and tannery (14%-16% frequency in the air). The presence of the gene encoding the Alt a 1 protein has been detected for the strains: Alternaria alternata, A. lini, A. limoniasperae A. nobilis and A. tenuissima. Environmental strains produced Alt a 1 at higher concentrations (1.103-6.528 ng/mL) than a ATCC strain (0.551-0.975 ng/mL). It has been shown that the homogenization of the mycelium and the use of ultrafiltration allow a considerable increase of Alt a 1 concentration. Variations in the production of Alt a 1 protein, depend on the strain and extraction methods. These studies revealed no impact of the technical material from the workplaces on the production of Alt a 1 protein. PMID:25689994

  15. Immortality in view of Maimonides and Spinoza

    Directory of Open Access Journals (Sweden)

    Morteza Shajari

    2014-12-01

    Full Text Available Desire for immortality can be seen as the essential natural impulse. Therefore, different religions and thinkers have attempted to see the issue from different viewpoints. The great Jewish philosopher. Maimonides, due to deep fixation to Judaism, has tried to express their issues to be consistent with the Bible and his own community believes. He, in his discussion of resurrection, believed to three basic steps: The Messiah, the resurrection, and the world hereafter. His standpoint of eternity is dedicated to the hereafter. And we can be immortalized only by acting and teachings in accordance with the Bible and righteousness. Like Maimonides, Spinoza – the other Jewish philosopher - considered the immortality as Ultimate bliss through which the “immutable and eternal love of God" can be achieved. In his opinion, a person reaches this stage, when the lusts and emotions can reasonably be overcome, and also, when the power and anger and contempt and disregard others will respond with love and dignity. Thus, a man can be reached its proper perfection and immortality is reached. The difference between these two philosophers is that Maimonides believes through "actual intellect" -that is Emanation of the active intellect- can be immortalized but, for Spinoza, eternity can be reached through the adequate Ideas.

  16. Network signatures of cellular immortalization in human lymphoblastoid cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Sung-Mi; Jung, So-Young; Nam, Hye-Young; Kim, Hye-Ryun; Lee, Mee-Hee; Kim, Jun-Woo; Han, Bok-Ghee [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Osong 363-951 (Korea, Republic of); Jeon, Jae-Pil, E-mail: jaepiljeon@hanmail.net [Division of Brain Diseases, Center for Biomedical Science, Korea National Institute of Health, Osong 363-951 (Korea, Republic of)

    2013-11-15

    Highlights: •We identified network signatures of LCL immortalization from transcriptomic profiles. •More than 41% of DEGs are possibly regulated by miRNAs in LCLs. •MicroRNA target genes in LCLs are involved in apoptosis and immune-related functions. •This approach is useful to find functional miRNA targets in specific cell conditions. -- Abstract: Human lymphoblastoid cell line (LCL) has been used as an in vitro cell model in genetic and pharmacogenomic studies, as well as a good model for studying gene expression regulatory machinery using integrated genomic analyses. In this study, we aimed to identify biological networks of LCL immortalization from transcriptomic profiles of microRNAs and their target genes in LCLs. We first selected differentially expressed genes (DEGs) and microRNAs (DEmiRs) between early passage LCLs (eLCLs) and terminally differentiated late passage LCLs (tLCLs). The in silico and correlation analysis of these DEGs and DEmiRs revealed that 1098 DEG–DEmiR pairs were found to be positively (n = 591 pairs) or negatively (n = 507 pairs) correlated with each other. More than 41% of DEGs are possibly regulated by miRNAs in LCL immortalizations. The target DEGs of DEmiRs were enriched for cellular functions associated with apoptosis, immune response, cell death, JAK–STAT cascade and lymphocyte activation while non-miRNA target DEGs were over-represented for basic cell metabolisms. The target DEGs correlated negatively with miR-548a-3p and miR-219-5p were significantly associated with protein kinase cascade, and the lymphocyte proliferation and apoptosis, respectively. In addition, the miR-106a and miR-424 clusters located in the X chromosome were enriched in DEmiR–mRNA pairs for LCL immortalization. In this study, the integrated transcriptomic analysis of LCLs could identify functional networks of biologically active microRNAs and their target genes involved in LCL immortalization.

  17. Probabilistic immortality of Cu damascene interconnects

    Science.gov (United States)

    Hau-Riege, Stefan P.

    2002-02-01

    We have studied electromigration short-line effects in Cu damascene interconnects through experiments on lines of various lengths L, stressed at a variety of current densities j, and embedded in different dielectric materials. We observed two modes of resistance evolution: Either the resistance of the lines remains constant for the duration of the test, so that the lines are considered immortal, or the lines fail due to abrupt open-circuit failure. The resistance was not observed to gradually increase and then saturate, as commonly observed in Al-based interconnects, because the barrier is too thin and resistive to serve as a redundant current path should voiding occur. The critical stress for void nucleation was found to be smaller than 41 MPa, since voiding occurred even under the mildest test conditions of j=2 MA/cm2 and L=10.5 μm at 300 °C. A small fraction of short Cu lines failed even at low current densities, which deems necessary a concept of probabilistic immortality rather than deterministic immortality. Experiments and modeling suggest that the probability of immortality is described by (jL2/B), where B is the effective elastic modulus of the metallization scheme. By contrast, the immortality of Al-based interconnects with shunt layers is described by (jL) if no voids nucleate, and (jL/B) if voids do nucleate. Even though the phenomenology of short-line effects differs for Al- and Cu-based interconnects, the immortality of interconnects of either materials system can be explained by the phenomena of nucleation barriers for void formation and void-growth saturation. The differences are due solely to the absence of a shunt layer and the low critical stress for void nucleation in the case of Cu.

  18. Selective expression of mutated p53 in human cells immortalized with either 4-nitroquinoline 1-oxide or 60Co gamma rays

    International Nuclear Information System (INIS)

    Many studies on in vitro transformation of human cells indicate that the cells must be immortalized before they can be neoplastically transformed, indicating that immortalization is a critical step in multistep neoplastic transformation of human cells. We immortalized three human cell lines by repeated treatment with either 60Co gamma rays or a chemical carcinogen, 4-nitroquinoline 1-oxide, and found that all three immortalized cell lines have mutations in the tumor suppressor gene, p53. Direct sequencing of the reverse-transcribed mRNA and immunoprecipitation of p53 protein revealed that mutant p53 is selectively expressed in all the immortalized cell lines, whereas the genomic fragments of the immortalized cells contain wild-type and mutated p53 alleles. Although the mutated p53 is selectively expressed in the immortalized cells, expression of the wild-type p53 was induced by treatment of the cells with a hypomethylating reagent, 5-azacytidine, indicating that the wild-type p53 allele might be inactivated by hypermethylation of DNA. Actually, the entire genomic locus including the promoter region of p53 is hypermethylated in all the immortalized cell lines. Expression and phosphorylation of Rb was normal in these three cell lines. Thus, inactivation of both wild type p53 alleles and selective expression of mutated p53 seem to be key factors in the immortalization of human fibroblasts. (author)

  19. Atenció a les altes capacitats

    OpenAIRE

    Asenjo Luque, Montse

    2012-01-01

    Davant dels diferents criteris sobre l'atenció a les altes capacitats, aquest estudi pretén contrastar com el sistema educatiu actual fa front a un possible cas en un centre de primària de Girona, de quina manera es mobilitza i dóna resposta a aquests tipus de necessitats educatives, enfront referents teòrics com l'educació lenta, inclusiva i constructivista entesa sobre les bases de la psicologia positiva, que ens permetran posar en evidència l'actual sistema d'intervenció a les altes capaci...

  20. Telomere elongation in immortal human cells without detectable telomerase activity.

    OpenAIRE

    Bryan, T M; Englezou, A; J Gupta; Bacchetti, S; Reddel, R. R.

    1995-01-01

    Immortalization of human cells is often associated with reactivation of telomerase, a ribonucleoprotein enzyme that adds TTAGGG repeats onto telomeres and compensates for their shortening. We examined whether telomerase activation is necessary for immortalization. All normal human fibroblasts tested were negative for telomerase activity. Thirteen out of 13 DNA tumor virus-transformed cell cultures were also negative in the pre-crisis (i.e. non-immortalized) stage. Of 35 immortalized cell line...

  1. Education as Immortality: Toward the Rehabilitation of an Ideal.

    Science.gov (United States)

    Blacker, David

    1998-01-01

    Observes that immortality remains an important animating ideal for teaching and learning, despite being long neglected as theological or egoistic. Makes the case that the role of immortality in pedagogy has a long history in Western thought. Argues that individuals should recognize and address ways that longing for immortality shapes educators'…

  2. Progressive transformation of immortalized esophageal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Zhong-YingShen; Li-YanXu; Min-HuaChen; JianShen; Wei-JiaCai; YiZeng

    2002-01-01

    AIM:To investigate the progressive transformation of immortal cells of human fetal esophageal epithelium induced by human papillomavirus,and to examine biological criteria of sequential passage of cells,including cellular phenotype,proliferative rate,telomerase,chromosome and tumorigenicity.

  3. The (not so immortal strand hypothesis

    Directory of Open Access Journals (Sweden)

    Cristian Tomasetti

    2015-03-01

    Significance: Utilizing an approach that is fundamentally different from previous efforts to confirm or refute the immortal strand hypothesis, we provide evidence against non-random segregation of DNA during stem cell replication. Our results strongly suggest that parental DNA is passed randomly to stem cell daughters and provides new insight into the mechanism of DNA replication in stem cells.

  4. Immortalization of human myogenic progenitor cell clone retaining multipotentiality

    International Nuclear Information System (INIS)

    Human myogenic cells have limited ability to proliferate in culture. Although forced expression of telomerase can immortalize some cell types, telomerase alone delays senescence of human primary cultured myogenic cells, but fails to immortalize them. In contrast, constitutive expression of both telomerase and the E7 gene from human papillomavirus type 16 immortalizes primary human myogenic cells. We have established an immortalized primary human myogenic cell line preserving multipotentiality by ectopic expression of telomerase and E7. The immortalized human myogenic cells exhibit the phenotypic characteristics of their primary parent, including an ability to undergo myogenic, osteogenic, and adipogenic terminal differentiation under appropriate culture conditions. The immortalized cells will be useful for both basic and applied studies aimed at human muscle disorders. Furthermore, immortalization by transduction of telomerase and E7 represents a useful method by which to expand human myogenic cells in vitro without compromising their ability to differentiate

  5. Editorial ALT-J non-electronica

    Directory of Open Access Journals (Sweden)

    Gabriel Jacobs

    1997-12-01

    Full Text Available The ALT Executive Committee has discussed on a number of occasions the question of making ALT-J wholly available in electronic form on our Web site (at present only the editorial and abstracts of papers appear, and even of turning it into a full-blown electronic journal. I have gently but consistently opposed this move, on occasions to the intense irritation of some of my fellow members, and always at the risk of appearing to be a Luddite. Explicitly ('Who, if not we as learning technologists, should be in the forefront of the soon-to-happen electronic-journal revolution?' and implicitly ('It is estimated that within two years, paper-based journals will be considered the dinosaurs of the academic world', I have increasingly come under pressure to accede to an apparently unstoppable, apparently imminent change in the method and form of scholarly publication. I set out here my reasons for my continued resistance.

  6. Immortality in view of Maimonides and Spinoza

    OpenAIRE

    Morteza Shajari; Yousef Nozohur; Abbas Fanni Asl

    2014-01-01

    Desire for immortality can be seen as the essential natural impulse. Therefore, different religions and thinkers have attempted to see the issue from different viewpoints. The great Jewish philosopher. Maimonides, due to deep fixation to Judaism, has tried to express their issues to be consistent with the Bible and his own community believes. He, in his discussion of resurrection, believed to three basic steps: The Messiah, the resurrection, and the world hereafter. His standpoint of eternity...

  7. Die Altäre von Selinunt

    OpenAIRE

    Voigts, Clemens

    2014-01-01

    In der Dissertation wurden die Altäre von Selinunt, einer griechischen Kolonie auf Sizilien, mit den Methoden der Bauforschung untersucht. Die neun behandelten Brandopferaltäre sind monumentale Quaderbauten, die bis zu 20 m Länge erreichen. Sie stammen aus der Blütezeit Selinunts, dem 6. und 5. Jh. v. Chr. Die Bauten waren bereits im 19. und 20. Jh. freigelegt worden und wurden nun in Bauaufnahmen dokumentiert, zeichnerisch rekonstruiert und zeitlich eingeordnet. Dabei ließ sich an ihnen eine...

  8. SMARCAL1 Resolves Replication Stress at ALT Telomeres.

    Science.gov (United States)

    Cox, Kelli E; Maréchal, Alexandre; Flynn, Rachel Litman

    2016-02-01

    Cancer cells overcome replicative senescence by exploiting mechanisms of telomere elongation, a process often accomplished by reactivation of the enzyme telomerase. However, a subset of cancer cells lack telomerase activity and rely on the alternative lengthening of telomeres (ALT) pathway, a recombination-based mechanism of telomere elongation. Although the mechanisms regulating ALT are not fully defined, chronic replication stress at telomeres might prime these fragile regions for recombination. Here, we demonstrate that the replication stress response protein SMARCAL1 is a critical regulator of ALT activity. SMARCAL1 associates with ALT telomeres to resolve replication stress and ensure telomere stability. In the absence of SMARCAL1, persistently stalled replication forks at ALT telomeres deteriorate into DNA double-strand breaks promoting the formation of chromosome fusions. Our studies not only define a role for SMARCAL1 in ALT telomere maintenance, but also demonstrate that resolution of replication stress is a crucial step in the ALT mechanism. PMID:26832416

  9. SMARCAL1 Resolves Replication Stress at ALT Telomeres

    Directory of Open Access Journals (Sweden)

    Kelli E. Cox

    2016-02-01

    Full Text Available Cancer cells overcome replicative senescence by exploiting mechanisms of telomere elongation, a process often accomplished by reactivation of the enzyme telomerase. However, a subset of cancer cells lack telomerase activity and rely on the alternative lengthening of telomeres (ALT pathway, a recombination-based mechanism of telomere elongation. Although the mechanisms regulating ALT are not fully defined, chronic replication stress at telomeres might prime these fragile regions for recombination. Here, we demonstrate that the replication stress response protein SMARCAL1 is a critical regulator of ALT activity. SMARCAL1 associates with ALT telomeres to resolve replication stress and ensure telomere stability. In the absence of SMARCAL1, persistently stalled replication forks at ALT telomeres deteriorate into DNA double-strand breaks promoting the formation of chromosome fusions. Our studies not only define a role for SMARCAL1 in ALT telomere maintenance, but also demonstrate that resolution of replication stress is a crucial step in the ALT mechanism.

  10. Senescence and immortality in hepatocellular carcinoma.

    Science.gov (United States)

    Ozturk, Mehmet; Arslan-Ergul, Ayca; Bagislar, Sevgi; Senturk, Serif; Yuzugullu, Haluk

    2009-12-01

    Cellular senescence is a process leading to terminal growth arrest with characteristic morphological features. This process is mediated by telomere-dependent, oncogene-induced and ROS-induced pathways, but persistent DNA damage is the most common cause. Senescence arrest is mediated by p16(INK4a)- and p21(Cip1)-dependent pathways both leading to retinoblastoma protein (pRb) activation. p53 plays a relay role between DNA damage sensing and p21(Cip1) activation. pRb arrests the cell cycle by recruiting proliferation genes to facultative heterochromatin for permanent silencing. Replicative senescence that occurs in hepatocytes in culture and in liver cirrhosis is associated with lack of telomerase activity and results in telomere shortening. Hepatocellular carcinoma (HCC) cells display inactivating mutations of p53 and epigenetic silencing of p16(INK4a). Moreover, they re-express telomerase reverse transcriptase required for telomere maintenance. Thus, senescence bypass and cellular immortality is likely to contribute significantly to HCC development. Oncogene-induced senescence in premalignant lesions and reversible immortality of cancer cells including HCC offer new potentials for tumor prevention and treatment. PMID:19070423

  11. TEAM TEACHING IN JAPAN FROM THE PERSPECTIVES OF THE ALTs, THE JTEs, AND THE STUDENTS

    Directory of Open Access Journals (Sweden)

    Andrea Ann Johannes

    2012-07-01

    Full Text Available This case study explores team teaching in Japan from the perspectives of JTEs (Japanese English Teachers, ALTs (Assistant Language Teachers, and students. Special focus is attributed to teachers and students’ perceptions of ALT and JTE roles. To determine the perspectives of all three participants, 112 students, 4 JTES and 2 ALTs from a Japanese high school in Chiba Prefecture were surveyed. Fieldwork was conducted over a ten-day period at the research site in 2009 to collect data in the form of questionnaires, interviews, and class observations. The findings indicate more of a mismatch between students’ perceptions of their teachers’ roles than between teachers. The results also reveal the students prefer a combination of both teachers and find team-taught classes more beneficial to developing their English skills.

  12. Relationship between body surface area and ALT normalization after long-term lamivudine treatment

    Institute of Scientific and Technical Information of China (English)

    Makoto Nakamuta; Hironori Sakai; Kazuhiro Takahashi; Koichi Azuma; Shinji Shimoda; Kazuhiro Kotoh; Munechika Enjoji; Jun Hayashi; Shusuke Morizono; Yuichi Tanabe; Eiji Kajiwara; Junya Shimono; Akihide Masumoto; Toshihiro Maruyama; Norihiro Furusyo; Hideyuki Nomura

    2005-01-01

    AIM: To further evaluate the relationship between BSA and the effects of lamivudine in a greater number of cases and over a longer period of observation than in our previous evaluation.METHODS: We evaluated 249 patients with chronic hepatitis B. The effects of treatment for one year (n = 249),two years (n = 147), and three years (n = 72) were evaluated from the levels of serum ALT and HBV-DNA,as biological and virological effects (undetectable levels by PCR), respectively. Moreover, several variables that could influence the response to treatment, including ALT,albumin, bilirubin, platelet counts, BSA, HBV-DNA, and HBeAg were analyzed.RESULTS: For 1-year treatment, multivariate analysis revealed that BSA (P=0.0002) was the only factor for the biological effect, and that ALT (P = 0.0017), HBVDNA (P = 0.0004), and HBeAg (P = 0.0021) were independent factors for the virological effect. For 2-year treatment, multivariate analysis again showed that BSA(P = 0.0147) was the only factor for the biological effect,and that ALT (P = 0.0192) and HBeAg (P = 0.0428) were independent factors for the virological effect. For 3-year treatment, multivariate analysis, however, could not reveal BSA (P = 0.0730) as a factor for the normalization of ALT levels.CONCLUSION: BSA is a significant predictor for the normalizing the effect of lamivudine therapy on ALT for an initial 2-year period, suggesting that lamivudine dosage should be based on the individual BSA.

  13. Effects of BRCA2 deficiency on telomere recombination in non-ALT and ALT cells

    Directory of Open Access Journals (Sweden)

    Sapir Ester

    2011-12-01

    Full Text Available Abstract Background Recent studies suggest that BRCA2 affects telomere maintenance. Interestingly, anti cancer treatments that involve BRCA2 and telomerase individually are currently being explored. In the light of the above recent studies their combinatorial targeting may be justified in the development of future treatments. In order to investigate effects of BRCA2 that can be explored for this combinatorial targeting we focused on the analysis of recombination rates at telomeres by monitoring T-SCEs (Telomere Sister Chromatid Exchanges. Results We observed a significant increase in T-SCE frequencies in four BRCA2 defective human cell lines thus suggesting that BRCA2 suppresses recombination at telomeres. To test this hypothesis further we analyzed T-SCE frequencies in a set of Chinese hamster cell lines with or without functional BRCA2. Our results indicate that introduction of functional BRCA2 normalizes frequencies of T-SCEs thus supporting the notion that BRCA2 suppresses recombination at telomeres. Given that ALT (Alternative Lengthening of Telomeres positive cells maintain telomeres by recombination we investigated the effect of BRCA2 depletion in these cells. Our results show that this depletion causes a dramatic reduction in T-SCE frequencies in ALT positive cells, but not in non-ALT cells. Conclusion BRCA2 suppresses recombination at telomeres in cells that maintain them by conventional mechanisms. Furthermore, BRCA2 depletion in ALT positive cells reduces high levels of T-SCEs normally found in these cells. Our results could be potentially important for refining telomerase-based anti-cancer therapies.

  14. Absence of oncogenic transformation despite acquisition of cytogenetic aberrations in long-term cultured telomerase-immortalized human fetal hepatocytes.

    Science.gov (United States)

    Haker, Björn; Fuchs, Sigrid; Dierlamm, Judith; Brümmendorf, Tim H; Wege, Henning

    2007-10-18

    As a culture model to study hepatocarcinogenesis, telomerase-immortalized human fetal hepatocytes were monitored for karyotype changes evolving in long-term culture and development of functional defects in DNA damage response. G-banding revealed acquisition of characteristic karyotype abnormalities, e.g., trisomy 7 and monosomy X, in two independently immortalized and cultured populations after 80-100 population doublings. Interestingly, the detected aneuploidies resemble some of the genetic events observed in hepatocellular cancer. However, these genetic changes were not sufficient to induce oncogenic transformation reflected by absence of anchorage-independent growth. Furthermore, long-term cultured telomerase-immortalized cells preserved p53 expression levels and effective p53-mediated damage response. PMID:17630152

  15. Histopathological grading and staging in liver biopsies of Hepatitis-C patients and their association with ALT levels

    International Nuclear Information System (INIS)

    Objective: To perform the histological evaluation of liver biopsies and see its association with the serological levels of ALT. Methodology: This was a prospective study based on liver biopsies of fifty hepatitis C patients, whose serum ALT levels were also estimated. H and E stained slides were examined to determine the histological activity and fibrosis score. Results: Grade 1 activity was found in 44% of patients; whereas 42% had an activity of grade 3. About 44% cases having grade 1 activity had a mean ALT of 52.3 U/L while 42% cases having severe activity had a mean ALT of 76.14 U/L. The present study revealed a significant relationship of ALT with fibrosis (p < 0.005). A steady and proportional rise in mean age with increasing score of fibrosis stage was also evident. Conclusion: Higher ALT levels are associated with more pronounced forms of necroinflammatory activity; however normal ALT level does not rule out severity of the disease suggesting that all such patients require liver biopsy to unearth clinically subtle but advanced liver disease. (author)

  16. Stamps of New China: The Eight Immortals Cross the Sea

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    On July 30, 2004, the State Postal Bureau issued its first asymmetrical perforated stamp in tnbute to the popular tale of how the Eight Immortals Crossed the Sea. The Eight Immortals are the most important figures in Chinese Taoist mythology. Each carried with them a magical object: a drum, a fan, a sword, a gourd, a bamboo flute, castanets, a basket of flowers and a lotus. Wherever they went they helped the weak and poor, punished evil-doers and encouraged people to do good. Immortality was their reward for such good deeds.

  17. 15th Incontri di Fisica delle Alte Energie

    CERN Document Server

    2016-01-01

    La XV Edizione di IFAE - Incontri di Fisica delle Alte Energie - si terrà presso il Dipartimento di Fisica dell'Università di Genova L'edizione 2016 comprenderà numerose sessioni dedicate alla discussione degli aspetti di maggiore interesse attuale e di prospettiva nella fisica delle alte energie.

  18. Cilia containing 9 + 2 structures grown from immortalized cells

    Institute of Scientific and Technical Information of China (English)

    Ming Zhang; Jose G Assouline

    2007-01-01

    Cilia depend on their highly differentiated structure, a 9 + 2 arrangement, to remove particles from the lung and to transport reproductive cells. Immortalized cells could potentially be of great use in cilia research. Immortalization of cells with cilia structure containing the 9 + 2 arrangement might be able to generate cell lines with such cilia structure. However, whether immortalized cells can retain such a highly differentiated structure remains unclear. Here we demonstrate that (1) using E1a gene transfection, tracheal cells are immortalized; (2) interestingly, in a gel culture the immortalized cells form spherical aggregations within which a lumen is developed; and (3) surprisingly, inside the aggregation, cilia containing a 9 + 2 arrangement grow from the cell's apical pole and protrude into the lumen. These results may influence future research in many areas such as understanding the mechanisms of cilia differentiation, cilia generation in other existing cell lines, cilia disorders, generation of other highly differentiated structures besides cilia using the gel culture,immortalization of other ciliated cells with the E1a gene, development of cilia motile function, and establishment of a research model to provide uniform ciliated cells.

  19. Molecular and Cellular Evidence for the Alternative Lengthening of Telomeres (ALT) Mechanism in Chicken

    OpenAIRE

    O'Hare, T.H.; Delany, M. E.

    2011-01-01

    Telomere maintenance is an important genetic mechanism controlling cellular proliferation. Normally, telomeres are maintained by telomerase which is downregulated upon cellular differentiation in most somatic cell lineages. Telomerase activity is upregulated in immortalized cells and cancers to support an infinite lifespan and uncontrolled cell growth; however, some immortalized and transformed cells lack telomerase activity. Telomerase-negative tumors and immortalized cells utilize an altern...

  20. PISCES and ALT-II: Juelich PSI papers

    Energy Technology Data Exchange (ETDEWEB)

    Conn, R.W.; Hirooka, Y.; LaBombard, B.; Moyer, R.; Goebel, D.M.; Leung, W.K.; Nygren, R.E.; Corbett, W.J.; Lehmer, R.; Ra, Y.; Tynan, G.; Dippel, K.H.; Finken, K.H.; Hardkte, A.; Kohlhaas, W.; Wolf, G.; Vandenplas, P.; Messian, M.; Van Oost, G.; Weynants, R.; Franconi, E.; Miyahara, A.; Sagara, A.; Gauster, W.B.; Koski, J.A.; McGrath, R.T.; Watkins, J.G.; Malinowski, M.E.

    1988-08-01

    This publication comprises papers from the PISCES and ALT-II Programs at UCLA which were presented at the International Plasma Surface Interactions Meeting held in Juelich, FRG, on May 2-6, 1988. A list of publications from the PISCES and ALT-II contained in this report are: Deuterium pumping and erosion behavior of selected graphite materials under high flux plasma bombardment in PISCES; Erosion and redeposition behavior of selected NET-candidate materials under high-flux hydrogen, deuterium plasma bombardment in PISCES; Presheath profiles in simulated tokamak edge plasmas; Boundary asymmetries and plasma flow to the ALT-II toroidal belt pump limiter; ALT-II toroidal belt pump limiter performance in TEXTOR; and An in-situ spectroscopic erosion yield measurement with applications to sputtering and surface morphology alterations.

  1. SMARCAL1 Resolves Replication Stress at ALT Telomeres

    OpenAIRE

    Kelli E. Cox; Alexandre Maréchal; Rachel Litman Flynn

    2016-01-01

    Cancer cells overcome replicative senescence by exploiting mechanisms of telomere elongation, a process often accomplished by reactivation of the enzyme telomerase. However, a subset of cancer cells lack telomerase activity and rely on the alternative lengthening of telomeres (ALT) pathway, a recombination-based mechanism of telomere elongation. Although the mechanisms regulating ALT are not fully defined, chronic replication stress at telomeres might prime these fragile regions for recombina...

  2. In Vitro Endothelialization Test of Biomaterials Using Immortalized Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Ken Kono

    Full Text Available Functionalizing biomaterials with peptides or polymers that enhance recruitment of endothelial cells (ECs can reduce blood coagulation and thrombosis. To assess endothelialization of materials in vitro, primary ECs are generally used, although the characteristics of these cells vary among the donors and change with time in culture. Recently, primary cell lines immortalized by transduction of simian vacuolating virus 40 large T antigen or human telomerase reverse transcriptase have been developed. To determine whether immortalized ECs can substitute for primary ECs in material testing, we investigated endothelialization on biocompatible polymers using three lots of primary human umbilical vein endothelial cells (HUVEC and immortalized microvascular ECs, TIME-GFP. Attachment to and growth on polymer surfaces were comparable between cell types, but results were more consistent with TIME-GFP. Our findings indicate that TIME-GFP is more suitable for in vitro endothelialization testing of biomaterials.

  3. Genes involved in immortalization of human mammary cells

    Energy Technology Data Exchange (ETDEWEB)

    Stampfer, Martha R.; Yaswen, Paul

    2001-09-27

    Breast cancer progression is characterized by inappropriate cell growth. Normal cells cease growth after a limited number of cell divisions--a process called cellular senescence-while tumor cells may acquire the ability to proliferate indefinitely (immortality). Inappropriate expression of specific oncogenes in a key cellular signaling pathway (Ras, Raf) can promote tumorigenicity in immortal cells, while causing finite lifespan cells to undergo a rapid senescence-like arrest. We have studied when in the course of transformation of cultured human mammary epithelial cells (HMEC), the response to overexpressed oncogenic Raf changes from being tumor-suppressive to tumor enhancing, and what are the molecular underpinnings of this response. Our data indicate: (1) HMEC acquire the ability to maintain growth in the presence of oncogenic Raf not simply as a consequence of overcoming senescence, but as a result of a newly discovered step in the process of immortal transformation uncovered by our lab, termed conversion. Immortal cells that have not undergone conversion (e.g., cells immortalized by exogenous introduction of the immortalizing enzyme, telomerase) remain growth inhibited. (2) Finite lifespan HMEC growth arrest in response to oncogenic Raf using mediators of growth inhibition that are very different from those used in response to oncogenic Raf by rodent cells and certain other human cell types, including the connective tissue cells from the same breast tissue. While many diverse cell types appear to have in common a tumor-suppressive response to this oncogenic signal, they also have developed multiple mechanisms to elicit this response. Understanding how cancer cells acquire the crucial capacity to be immortal and to abrogate normal tumor-suppressive mechanisms may serve both to increase our understanding of breast cancer progression, and to provide new targets for therapeutic intervention. Our results indicate that normal HMEC have novel means of enforcing a Raf

  4. Measuring an Individual's Investment in the Future: Symbolic Immortality, Sensation Seeking, and Psychic Numbness.

    Science.gov (United States)

    Mathews, Robert C.; Mister, Rena D.

    1988-01-01

    Operationalized Lifton's constructs of symbolic immortality and developed instrument to measure individual's needs for symbolic immortality in Lifton's five modes (biological, religious, nature, creative, experiential) in study which also examined age effects on needs for symbolic immortality and relation between sensation seeking and symbolic…

  5. Locus of Control and Level of Conflict as Correlates of Immortality Orientation.

    Science.gov (United States)

    O'Dowd, William

    1985-01-01

    Assessed the orientation of 14 male professors toward immortality as a psychological motive. Results showed a generally low conscious concern with immortality issues; however, respondents who have accepted some sort of immortality show a more internal locus of control and better adjustment. (JAC)

  6. The French Academy: Arbitrator of Taste, Order, Genius--Immortality.

    Science.gov (United States)

    Buzash, Michael D.

    The French Academy is the oldest of the scholarly societies of France. Its ideals and preferences of order, genius, and immortality have influenced the schools, conservatories, universities, and archives and the intellectual and artistic tastes of the time. Its foundation was laid by nine lettered, well-educated laymen and ecclesiastics around…

  7. Symbolic Immortality in Ordinary Contexts: Impediments to the Nuclear Era.

    Science.gov (United States)

    Schmitt, Raymond L.

    1982-01-01

    Lifton's writings indicate that fear of nuclear holocaust has severely impaired and threatens to negate traditional modes of symbolic immortality in America. Lifton's research, however, has been limited to extreme contexts. Data were triangulated in four distinctive American contexts. Found substantial negative evidence of Lifton's suspicions in…

  8. The Golden Bough: Literature and the Idea of Immortality.

    Science.gov (United States)

    Klotz, Kenneth

    1979-01-01

    All works of literature reflect man's obsession with death and his creative attempts to evade or postpone it. Art cannot solve the problem, but within the limits of human capabilities, we come to art, whether as artists or audience, for our own small share in the "intimations of immortality." (Author/SJL)

  9. Antioxidant and antifatigue activities of Polygonatum Alte-lobatum Hayata rhizomes in rats.

    Science.gov (United States)

    Horng, Chi-Ting; Huang, Jon-Kway; Wang, Hui-Yun; Huang, Chi-Chang; Chen, Fu-An

    2014-11-01

    Polygonatum alte-lobatum Hayata, a rhizomatous perennial herb, belongs to the Liliaceae family and is endemic to Taiwan. We investigated the antioxidant and anti-fatigue activities of P. alte-lobatum in exercised rats. Levels of polyphenols, flavonoids and polysaccharides and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging activity were measured in extracts of P. alte-lobatum (EPA). Sprague-Dawley rats were randomly divided into four groups for 8-week treatment with vehicle (control) and low-, medium-, and high-dose EPA (LEPA, MEPA, HEPA; 0, 75, 150, and 375 mg/kg/day, respectively). Exercise performance was evaluated by exhaustive treadmill exercise time and by changes in body composition and biochemical variables at the end of the experiment. EPA contained polyphenols, flavonoids and polysaccharides, with polysaccharide content at least 26 times greater than that of polyphenols and flavonoids. Trend analysis revealed that EPA dose-dependently scavenged DPPH free radicals. EPA treatment dose-dependently increased endurance running time to exhaustion and superoxide dismutase activity and total antioxidant ability of blood. EPA dose-dependently decreased serum urea nitrogen and malondialdehyde levels after exercise. Hepatic glycogen content, an important energy source for exercise, was significantly increased with EPA treatment. EPA could be a potential agent with an anti-fatigue pharmacological function. PMID:25421533

  10. Antioxidant and Antifatigue Activities of Polygonatum Alte-lobatum Hayata Rhizomes in Rats

    Directory of Open Access Journals (Sweden)

    Chi-Ting Horng

    2014-11-01

    Full Text Available Polygonatum alte-lobatum Hayata, a rhizomatous perennial herb, belongs to the Liliaceae family and is endemic to Taiwan. We investigated the antioxidant and anti-fatigue activities of P. alte-lobatum in exercised rats. Levels of polyphenols, flavonoids and polysaccharides and 2,2-diphenyl-1-picrylhydrazyl (DPPH free-radical scavenging activity were measured in extracts of P. alte-lobatum (EPA. Sprague-Dawley rats were randomly divided into four groups for 8-week treatment with vehicle (control and low-, medium-, and high-dose EPA (LEPA, MEPA, HEPA; 0, 75, 150, and 375 mg/kg/day, respectively. Exercise performance was evaluated by exhaustive treadmill exercise time and by changes in body composition and biochemical variables at the end of the experiment. EPA contained polyphenols, flavonoids and polysaccharides, with polysaccharide content at least 26 times greater than that of polyphenols and flavonoids. Trend analysis revealed that EPA dose-dependently scavenged DPPH free radicals. EPA treatment dose-dependently increased endurance running time to exhaustion and superoxide dismutase activity and total antioxidant ability of blood. EPA dose-dependently decreased serum urea nitrogen and malondialdehyde levels after exercise. Hepatic glycogen content, an important energy source for exercise, was significantly increased with EPA treatment. EPA could be a potential agent with an anti-fatigue pharmacological function.

  11. Staphylococcal superantigens stimulate immortalized human adipocytes to produce chemokines.

    Directory of Open Access Journals (Sweden)

    Bao G Vu

    Full Text Available BACKGROUND: Human adipocytes may have significant functions in wound healing and the development of diabetes through production of pro-inflammatory cytokines after stimulation by gram-negative bacterial endotoxin. Diabetic foot ulcers are most often associated with staphylococcal infections. Adipocyte responses in the area of the wound may play a role in persistence and pathology. We studied the effect of staphylococcal superantigens (SAgs on immortalized human adipocytes, alone and in the presence of bacterial endotoxin or staphylococcal α-toxin. METHODOLOGY/PRINCIPAL FINDINGS: Primary non-diabetic and diabetic human preadipocytes were immortalized by the reverse transcriptase component of telomerase (TERT and the E6/E7 genes of human papillomavirus. The immortal cells were demonstrated to have properties of non-immortalized pre-adipocytes and could be differentiated into mature and functional adipocytes. Differentiated adipocytes exposed to staphylococcal SAgs produced robust levels of cytokines IL-6 and IL-8, but there were no significant differences in levels between the non-diabetic and diabetic cells. Cytokine production was increased by co-incubation of adipocytes with SAgs and endotoxin together. In contrast, α-toxin alone was cytotoxic at high concentrations, but, at sub-cytotoxic doses, did not stimulate production of IL-6 and IL-8. CONCLUSIONS/SIGNIFICANCE: Endotoxin has been proposed to contribute to diabetes through enhanced insulin resistance after chronic exposure and stimulation of adipocytes to produce cytokines. Our data indicate staphylococcal SAgs TSST-1 and SEB alone and in combination with bacterial endotoxin also stimulate adipocytes to produce cytokines and thus may contribute to the inflammatory response found in chronic diabetic ulcers and in the systemic inflammation that is associated with the development and persistence of diabetes. The immortal human pre-adipocytes reported here will be useful for studies to

  12. Telomerase-Independent Paths to Immortality in Predictable Cancer Subtypes

    Directory of Open Access Journals (Sweden)

    Stephen T Durant

    2012-01-01

    Full Text Available The vast majority of cancers commandeer the activity of telomerase - the remarkable enzyme responsible for prolonging cellular lifespan by maintaining the length of telomeres at the ends of chromosomes. Telomerase is only normally active in embryonic and highly proliferative somatic cells. Thus, targeting telomerase is an attractive anti-cancer therapeutic rationale currently under investigation in various phases of clinical development. However, previous reports suggest that an average of 10-15% of all cancers lose the functional activity of telomerase and most of these turn to an Alternative Lengthening of Telomeres pathway (ALT. ALT-positive tumours will therefore not respond to anti-telomerase therapies and there is a real possibility that such drugs would be toxic to normal telomerase-utilising cells and ultimately select for resistant cells that activate an ALT mechanism. ALT exploits certain DNA damage response (DDR components to counteract telomere shortening and rapid trimming. ALT has been reported in many cancer subtypes including sarcoma, gastric carcinoma, central nervous system malignancies, subtypes of kidney (Wilm's Tumour and bladder carcinoma, mesothelioma, malignant melanoma and germ cell testicular cancers to name but a few. A recent heroic study that analysed ALT in over six thousand tumour samples supports this historical spread, although only reporting an approximate 4% prevalence. This review highlights the various methods of ALT detection, unravels several molecular ALT models thought to promote telomere maintenance and elongation, spotlights the DDR components known to facilitate these and explores why certain tissues are more likely to subvert DDR away from its usually protective functions, resulting in a predictive pattern of prevalence in specific cancer subsets.

  13. Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells

    OpenAIRE

    Conomos, Dimitri; Stutz, Michael D.; Hills, Mark; Neumann, Axel A.; Bryan, Tracy M.; Reddel, Roger R; Hilda A Pickett

    2012-01-01

    Telomeres in cells that use the recombination-mediated alternative lengthening of telomeres (ALT) pathway elicit a DNA damage response that is partly independent of telomere length. We therefore investigated whether ALT telomeres contain structural abnormalities that contribute to ALT activity. Here we used next generation sequencing to analyze the DNA content of ALT telomeres. We discovered that variant repeats were interspersed throughout the telomeres of ALT cells. We found that the C-type...

  14. Development of cancer-initiating cells and immortalized cells with genomic instability.

    Science.gov (United States)

    Yoshioka, Ken-Ichi; Atsumi, Yuko; Nakagama, Hitoshi; Teraoka, Hirobumi

    2015-03-26

    Cancers that develop after middle age usually exhibit genomic instability and multiple mutations. This is in direct contrast to pediatric tumors that usually develop as a result of specific chromosomal translocations and epigenetic aberrations. The development of genomic instability is associated with mutations that contribute to cellular immortalization and transformation. Cancer occurs when cancer-initiating cells (CICs), also called cancer stem cells, develop as a result of these mutations. In this paper, we explore how CICs develop as a result of genomic instability, including looking at which cancer suppression mechanisms are abrogated. A recent in vitro study revealed the existence of a CIC induction pathway in differentiating stem cells. Under aberrant differentiation conditions, cells become senescent and develop genomic instabilities that lead to the development of CICs. The resulting CICs contain a mutation in the alternative reading frame of CDKN2A (ARF)/p53 module, i.e., in either ARF or p53. We summarize recently established knowledge of CIC development and cellular immortality, explore the role of the ARF/p53 module in protecting cells from transformation, and describe a risk factor for genomic destabilization that increases during the process of normal cell growth and differentiation and is associated with the downregulation of histone H2AX to levels representative of growth arrest in normal cells. PMID:25815132

  15. Immortalization of human articular chondrocytes and induction of their phenotype

    Institute of Scientific and Technical Information of China (English)

    何清义; 李起鸿; 杨柳; 许建中

    2003-01-01

    Objective To immortalize human articular chondrocytes (HACs) using gene transfection and to maintain stable phenotype of transformed HACs after induction.Methods HACs were transfected with the retroviral vector pLXSN encoding human papillomavirus 16E7 (HPV16E7), and the transformed clones were sorted and proliferated. Karyotype analysis, clone forming tests and nude mice tumor forming tests were applied to check the characteristics of the transformation. Type Ⅱ collagen of transformed chondrocytes was inducted with free serum medium (FSM) supplemented with nutridoma-sp and ascorbate. Results Immortalized HACs were isolated with fifty passages achieved. The HPV16E7 transformed cells were confirmed to be benign. Induction of FSM with nutridoma-sp and ascorbate promoted type Ⅱ collagen of transformed chondrocytes to the high levels of normal chondrocytes. Conclusion HACs transformed with HPV16E7 survive for long periods in vitro, and type Ⅱ collagen can maintain stability after induction.

  16. Immortalized neural progenitor cells for CNS gene transfer and repair.

    Science.gov (United States)

    Martínez-Serrano, A; Björklund, A

    1997-11-01

    Immortalized multipotent neural stem and progenitor cells have emerged as a highly convenient source of tissue for genetic manipulation and ex vivo gene transfer to the CNS. Recent studies show that these cells, which can be maintained and genetically transduced as cell lines in culture, can survive, integrate and differentiate into both neurons and glia after transplantation to the intact or damaged brain. Progenitors engineered to secrete trophic factors, or to produce neurotransmitter-related or metabolic enzymes can be made to repopulate diseased or injured brain areas, thus providing a new potential therapeutic tool for the blockade of neurodegenerative processes and reversal of behavioural deficits in animal models of neurodegenerative diseases. With further technical improvements, the use of immortalized neural progenitors may bring us closer to the challenging goal of targeted and effective CNS repair.

  17. The Immortality of the Soul: History of a Political Argument

    OpenAIRE

    Miguel Saralegui

    2014-01-01

    The paper examines a fundamental and little studied issue of political theology: the relationship between the defense of the immortality of the soul and the preservation of public order. It carries out a historical survey of authors such as Pietro Pomponazzi and Thomas More, who resort to political reasons in order to defend it, and David Hume, who feels that there are no political grounds to support such a relationship. Finally, the article analyzes the arguments proposed to show that its...

  18. Stressed SIRT7: facing a crossroad of senescence and immortality.

    Science.gov (United States)

    Liu, Jun-Ping; Chen, Ruping

    2015-06-01

    SIRT7 with coenzyme NAD catalyzes protein de-acetylation. In stress response, SIRT7 regulates protein folding in mitochondria with unknown mechanisms. Decreases in SIRT7 entrain hematopoietic stem cell senescence, but increasing SIRT7 causes elevation of hematopoietic stem cell regenerative function. We discuss the recent findings on SIRT7 and its binding proteins, NRF1 and GABPβ1, in decision making between the choices of inducing cell aging and immortality. PMID:25970806

  19. Many-Worlds Interpretations Can Not Imply 'Quantum Immortality'

    OpenAIRE

    Mallah, Jacques

    2009-01-01

    The fallacy that the many worlds intepretation (MWI) of quantum mechanics implies certain survival in quantum Russian roulette-like situations (the 'Quantum Suicide' (QS) thought experiment) has become common enough that it is now necessary to publicly debunk this belief despite the risk of further publicizing it. 'Quantum Immortality' is an extension of the QS Fallacy (QSF) with some additional unlikely assumptions. The QS/QI ideas are examined here and shown to be false.

  20. Silicon soul: The vain dream of electronic immortality

    OpenAIRE

    Rougier, Nicolas P.

    2016-01-01

    International audience "In just over 30 years, humans will be able to upload their entire minds to computers and become digitally immortal." – Ray Kurzweil, Global Futures 2045 International Congress (2013). Without even considering the ethical, philosophical, social or legal scope of such a statement, it’s important to consider if it actually makes any sense. To try to give an educated guess, we have to move away from computer science and look at what biology and neuroscience can teach us...

  1. Neoplastic transformation of immortalized human epidermal keratinocytes by ionizing radiation.

    OpenAIRE

    Thraves, P; Salehi, Z; Dritschilo, A; Rhim, J S

    1990-01-01

    Efforts to investigate the progression of events that cause human cells to become neoplastic in response to ionizing radiation have been aided by the development of tissue culture systems of epithelial cells. In the present study, nontumorigenic human epidermal keratinocytes immortalized by adenovirus type 12 and simian virus 40 have been transformed by exposure to x-ray irradiation. Such transformants showed morphological alterations, formed colonies in soft agar, and induced carcinomas when...

  2. Koschei the immortal and anti-aging drugs

    OpenAIRE

    Blagosklonny, M V

    2014-01-01

    In Slavic folklore, Koschei the Immortal was bony, thin and lean. Was his condition caused by severe calorie restriction (CR)? CR deactivates the target of rapamycin pathway and slows down aging. But the life-extending effect of severe CR is limited by starvation. What if Koschei's anti-aging formula included rapamycin? And was rapamycin (or another rapalog) combined with commonly available drugs such as metformin, aspirin, propranolol, angiotensin II receptor blockers and angiotensin-convert...

  3. Role of SV40 Integration Site at Chromosomal Interval 1q21.1 in Immortalized CRL2504 Cells

    Science.gov (United States)

    Liu, Jinglan; Kaur, Gurpreet; Zhawar, Vikramjit K.; Zimonjic, Drazen B.; Popescu, Nicholas C.; Kandpal, Raj P.; Athwal, Raghbir S.

    2009-01-01

    We have applied a functional gene transfer strategy to demonstrate the importance of viral integration site in cellular immortalization. The large tumor antigen of SV40 is capable of extending the cellular life span by sequestering tumor suppressor proteins pRB and p53 in virus-transformed human cells. Although SV40-LT is essential, it is not sufficient for cellular immortalization, suggesting that additional alterations in cellular genes are required to attain infinite proliferation. We demonstrate here that the disruption of human chromosomal interval at 1q21.1, by SV40 integration, can be an essential step for cellular immortalization. The transfer of a 150Kb bacterial artificial chromosome (BAC) clone, RP364B14, corresponding to viral integration site in CRL2504 cells, reverted their immortal phenotype. Interestingly, the BAC transfer clones of CRL-2504 cells displayed characteristics of either senescence as shown by β-galactosidase activity or apoptosis as revealed by positive staining with M30 cytoDeath antibody. The SV40 integration at 1q21.1, in the vicinity of epidermal differentiation complex genes, resulted in the down-regulation of the filaggrin (FLG) gene that is part of the epidermal differentiation complex. FLG gene expression was restored to its normal levels in BAC transfer senescent and apoptotic clones. Our results suggest that the disruption of native genomic sequence by SV40 may alter expression of genes involved in senescence and apoptosis by modulating chromatin structure. These studies imply that identification of genes located in the vicinity of viral integration sites in human cancers may be helpful in developing new diagnostic and therapeutic strategies. PMID:19789346

  4. Alternative Liquid Fuels Simulation Model (AltSim).

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Ryan; Baker, Arnold Barry; Drennen, Thomas E.

    2009-12-01

    The Alternative Liquid Fuels Simulation Model (AltSim) is a high-level dynamic simulation model which calculates and compares the production and end use costs, greenhouse gas emissions, and energy balances of several alternative liquid transportation fuels. These fuels include: corn ethanol, cellulosic ethanol from various feedstocks (switchgrass, corn stover, forest residue, and farmed trees), biodiesel, and diesels derived from natural gas (gas to liquid, or GTL), coal (coal to liquid, or CTL), and coal with biomass (CBTL). AltSim allows for comprehensive sensitivity analyses on capital costs, operation and maintenance costs, renewable and fossil fuel feedstock costs, feedstock conversion ratio, financial assumptions, tax credits, CO{sub 2} taxes, and plant capacity factor. This paper summarizes the structure and methodology of AltSim, presents results, and provides a detailed sensitivity analysis. The Energy Independence and Security Act (EISA) of 2007 sets a goal for the increased use of biofuels in the U.S., ultimately reaching 36 billion gallons by 2022. AltSim's base case assumes EPA projected feedstock costs in 2022 (EPA, 2009). For the base case assumptions, AltSim estimates per gallon production costs for the five ethanol feedstocks (corn, switchgrass, corn stover, forest residue, and farmed trees) of $1.86, $2.32, $2.45, $1.52, and $1.91, respectively. The projected production cost of biodiesel is $1.81/gallon. The estimates for CTL without biomass range from $1.36 to $2.22. With biomass, the estimated costs increase, ranging from $2.19 per gallon for the CTL option with 8% biomass to $2.79 per gallon for the CTL option with 30% biomass and carbon capture and sequestration. AltSim compares the greenhouse gas emissions (GHG) associated with both the production and consumption of the various fuels. EISA allows fuels emitting 20% less greenhouse gases (GHG) than conventional gasoline and diesels to qualify as renewable fuels. This allows several of the

  5. Alternative Liquid Fuels Simulation Model (AltSim).

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Ryan; Baker, Arnold Barry; Drennen, Thomas E.

    2009-12-01

    The Alternative Liquid Fuels Simulation Model (AltSim) is a high-level dynamic simulation model which calculates and compares the production and end use costs, greenhouse gas emissions, and energy balances of several alternative liquid transportation fuels. These fuels include: corn ethanol, cellulosic ethanol from various feedstocks (switchgrass, corn stover, forest residue, and farmed trees), biodiesel, and diesels derived from natural gas (gas to liquid, or GTL), coal (coal to liquid, or CTL), and coal with biomass (CBTL). AltSim allows for comprehensive sensitivity analyses on capital costs, operation and maintenance costs, renewable and fossil fuel feedstock costs, feedstock conversion ratio, financial assumptions, tax credits, CO{sub 2} taxes, and plant capacity factor. This paper summarizes the structure and methodology of AltSim, presents results, and provides a detailed sensitivity analysis. The Energy Independence and Security Act (EISA) of 2007 sets a goal for the increased use of biofuels in the U.S., ultimately reaching 36 billion gallons by 2022. AltSim's base case assumes EPA projected feedstock costs in 2022 (EPA, 2009). For the base case assumptions, AltSim estimates per gallon production costs for the five ethanol feedstocks (corn, switchgrass, corn stover, forest residue, and farmed trees) of $1.86, $2.32, $2.45, $1.52, and $1.91, respectively. The projected production cost of biodiesel is $1.81/gallon. The estimates for CTL without biomass range from $1.36 to $2.22. With biomass, the estimated costs increase, ranging from $2.19 per gallon for the CTL option with 8% biomass to $2.79 per gallon for the CTL option with 30% biomass and carbon capture and sequestration. AltSim compares the greenhouse gas emissions (GHG) associated with both the production and consumption of the various fuels. EISA allows fuels emitting 20% less greenhouse gases (GHG) than conventional gasoline and diesels to qualify as renewable fuels. This allows several of the

  6. Rescue excavations on Alt-Laari settlement site, Tartumaa / Anti Lillak, Heiki Valk

    Index Scriptorium Estoniae

    Lillak, Anti

    2009-01-01

    Alt-Laari linnusasula tekkis nähtavasti rooma rauaajal. Kui Alt-Laari linnus oli kasutused arvatavasti I aastatuhandest II aastatuhandeni pKr. siis asula kestis edasi keskajal ning jäeti maha hiljemalt 14. sajandil

  7. Functional analysis of a novel human serotonin transporter gene promoter in immortalized raphe cells

    DEFF Research Database (Denmark)

    Mortensen, O V; Thomassen, M; Larsen, M B;

    1999-01-01

    To investigate the structural basis for genetic regulation of the human serotonin transporter gene, a 1.8 kb fragment upstream to the cap site was cloned and sequenced. The promoter possesses a polymorphic repeat region with 16 and 14 repeats, respectively. Both were cloned and characterized...... were found to possess the additional 379 bp fragment. The integrity of the promoter was furthermore confirmed by genomic Southern blotting. The promoter activity was analyzed by reporter gene assays in neuronal and non-neuronal serotonergic cell lines. In immortalized serotonergic raphe neurons, RN46A....... The promoter sequence revealed an internal 379 bp fragment not reported in previous publications. This novel fragment contains consensus sequences for several transcription factors including SpI and GATA. DNA from 48 unrelated individuals was PCR amplified, in this region, to test for allelic variations. All...

  8. Synthesis, Chiroptical Behavior, and Sensing of Carboxylic Acid Functionalized.Poly(phenylene ethynylene-alt-bithiophene)s

    OpenAIRE

    Vandeleene, Steven; Verswyvel, Michiel; Verbiest, Thierry; Koeckelberghs, Guy

    2010-01-01

    Several poly(phenylene ethynylene-alt-bithiophene)s with (chiral) nonfunctionalized substituents were synthesized with a variable phenylene ethynylene (PE) spacer length (up to 4 repeating units). The chiroptical behavior was evaluated with UV vis and circular dichroism (CD) spectroscopy, revealing a highly solvent-sensitive aggregate formation. Based on this high sensitivity, both chiral and achiral carboxylic acid functionalized analogues were prepared, of which the length of the spacer con...

  9. DSLR Double Star Astrometry Using an Alt-Az Telescope

    Science.gov (United States)

    Frey, Thomas; Haworth, David

    2014-07-01

    The goal of this project was to determine if the double star's angular separation and position angle measurements could be successfully measured with a motor driven, alt-azimuth Dobsonian-mounted Newtonian telescope (without a field rotator), and a digital single-lens reflex (DSLR) camera. Additionally, the project was constrained by using as much existing equipment as much as possible, including an Apple MacBook Pro laptop and a Canon T2i camera. This project was additionally challenging because the first author had no experience with astrophotography.

  10. Transcription profiles of non-immortalized breast cancer cell lines

    International Nuclear Information System (INIS)

    Searches for differentially expressed genes in tumours have made extensive use of array technology. Most samples have been obtained from tumour biopsies or from established tumour-derived cell lines. Here we compare cultures of non-immortalized breast cancer cells, normal non-immortalized breast cells and immortalized normal and breast cancer cells to identify which elements of a defined set of well-known cancer-related genes are differentially expressed. Cultures of cells from pleural effusions or ascitic fluids from breast cancer patients (MSSMs) were used in addition to commercially-available normal breast epithelial cells (HMECs), established breast cancer cell lines (T-est) and established normal breast cells (N-est). The Atlas Human Cancer 1.2 cDNA expression array was employed. The data obtained were analysed using widely-available statistical and clustering software and further validated through real-time PCR. According to Significance Analysis of Microarray (SAM) and AtlasImage software, 48 genes differed at least 2-fold in adjusted intensities between HMECs and MSSMs (p < 0.01). Some of these genes have already been directly linked with breast cancer, metastasis and malignant progression, whilst others encode receptors linked to signal transduction pathways or are otherwise related to cell proliferation. Fifty genes showed at least a 2.5-fold difference between MSSMs and T-est cells according to AtlasImage, 2-fold according to SAM. Most of these classified as genes related to metabolism and cell communication. The expression profiles of 1176 genes were determined in finite life-span cultures of metastatic breast cancer cells and of normal breast cells. Significant differences were detected between the finite life-span breast cancer cell cultures and the established breast cancer cell lines. These data suggest caution in extrapolating information from established lines for application to clinical cancer research

  11. The Immortality of the Soul: History of a Political Argument

    Directory of Open Access Journals (Sweden)

    Miguel Saralegui

    2014-08-01

    Full Text Available The paper examines a fundamental and little studied issue of political theology: the relationship between the defense of the immortality of the soul and the preservation of public order. It carries out a historical survey of authors such as Pietro Pomponazzi and Thomas More, who resort to political reasons in order to defend it, and David Hume, who feels that there are no political grounds to support such a relationship. Finally, the article analyzes the arguments proposed to show that its efficacy is conditioned by the historical situation.

  12. DNA asymmetry in stem cells - immortal or mortal?

    Science.gov (United States)

    Yadlapalli, Swathi; Yamashita, Yukiko M

    2013-09-15

    The immortal strand hypothesis proposes that stem cells retain a template copy of genomic DNA (i.e. an 'immortal strand') to avoid replication-induced mutations. An alternative hypothesis suggests that certain cells segregate sister chromatids non-randomly to transmit distinct epigenetic information. However, this area of research has been highly controversial, with conflicting data even from the same cell types. Moreover, historically, the same term of 'non-random sister chromatid segregation' or 'biased sister chromatid segregation' has been used to indicate distinct biological processes, generating a confusion in the biological significance and potential mechanism of each phenomenon. Here, we discuss the models of non-random sister chromatid segregation, and we explore the strengths and limitations of the various techniques and experimental model systems used to study this question. We also describe our recent study on Drosophila male germline stem cells, where sister chromatids of X and Y chromosomes are segregated non-randomly during cell division. We aim to integrate the existing evidence to speculate on the underlying mechanisms and biological relevance of this long-standing observation on non-random sister chromatid segregation.

  13. Mortal Ancestors, Immortal Images: Zhang Dai’s Biographical Portraits

    Directory of Open Access Journals (Sweden)

    Duncan M. Campbell

    2012-11-01

    Full Text Available Towards the end of his long life, the prolific late-Ming historian and essayist Zhang Dai 張岱 (1597-?1684 completed a book that he had been working on for many years. Entitled Portraits of the Eminent and Worthy Immortals of Zhejiang During the Ming Dynasty (You Ming yuyue san bu xiu tuzan 有明於越三不朽名賢圖贊 the book included the short biographies (with poetic panegyrics and portraits of 109 men and women of Zhang Dai’s hometown of Shaoxing, one of the epicentres of China’s élite cultural life. The book was organised according to the “Three Immortalities of Life”: moral force, meritorious service, and wise words. Zhang also included a number of his own friends and family members in this collection. This paper discusses aspects the relationship between text and image in this late-imperial Chinese work, both in the context of Zhang Dai’s practice as a biographer who had a strong visual sense and in regard to his particular historical plight as someone who had survived the collapse of one dynasty and who had lived on under its successor regime.

  14. Dying To Teach: The Educator's Search for Immortality. Advances in Contemporary Educational Thought Series, Volume 18.

    Science.gov (United States)

    Blacker, David J.

    This book offers both an intellectual history and a sustained argument for the inescapability of education's immortality agenda. It seeks a Hegelian synthesis of common ideas about living in one's students by giving them something of oneself, developing the image of immortality as an a-temporal, mythic, meaning-making, relational enterprise.…

  15. Immortalization capacity of HPV types is inversely related to chromosomal instability

    DEFF Research Database (Denmark)

    Schütze, Denise M; Krijgsman, Oscar; Snijders, Peter J F;

    2016-01-01

    by a crisis period, require more genetic host cell aberrations to facilitate immortalization than types that can immortalize without crisis. This may in part explain the observed differences in HPV-type prevalence in cervical cancers and emphasizes that changes in the host cell genome contribute to HPV...

  16. Effects of hTERT immortalization on osteogenic and adipogenic differentiation of dental pulp stem cells

    Directory of Open Access Journals (Sweden)

    Ikbale El-Ayachi

    2016-03-01

    Full Text Available These data relate to the differentiation of human dental pulp stem cells (DPSC and DPSC immortalized by constitutively expressing human telomerase reverse transcriptase (hTERT through both osteogenic and adipogenic lineages (i.e. to make bone producing and fat producing cells from these dental pulp stem cells. The data augment another study to characterize immortalized DPSC for the study of neurogenetic “Characterization of neurons from immortalized dental pulp stem cells for the study of neurogenetic disorders” [1]. Two copies of one typical control cell line (technical replicates were used in this study. The data represent the differentiation of primary DPSC into osteoblast cells approximately 60% more effectively than hTERT immortalized DPSC. Conversely, both primary and immortalized DPSC are poorly differentiated into adipocytes. The mRNA expression levels for both early and late adipogenic and osteogenic gene markers are shown.

  17. 22941 Cases of Blood Donor Screening Model of ALT%献血者22941例 ALT 初筛模式探讨

    Institute of Scientific and Technical Information of China (English)

    贺许华

    2013-01-01

    objective (ALT) unqualified and gender, age, occupation, type, body mass index, blood donation (BMI) and the relationship between life style, to explore the causes of elevated alt donors, establishment of donor alt screening model for blood donation, and provide scientific reference for recruitment. Methods td-1401a dry plate rapid detector for alt screening blood donors. Results The results of ALT in blood donors screening unqualified in male than in female P < 0.01 (χ2=110.840);different age donors, with the growth of the age of unqualified rate increased significantly P < 0.01 (χ2=280.110); different occupation, different types of blood donors have significant difference P < 0.01 ( χ2= 651.070, 416.490) blood donors; weight exceed the standard is the primary cause of alt failed P < 0.01 (χ2=764.390); lifestyle has become one of the factors of ALT in blood donors. Conclusion to strengthen the propaganda and education of health knowledge of blood donation, blood donors and different scales for different blood donation activities, the establishment of alt screening model, carry out alt screening, from low risk population were recruited donors, can effectively reduce the alt failure rate, saving precious blood resources.%目的:了解无偿献血者谷丙转氨酶(alt)不合格与性别、年龄、职业、献血类型、体重指数(BMi)及生活方式等的关系,探讨献血者 alt 升高的原因,建立献血者 alt 初筛模式,为无偿献血招募工作提供科学的参考依据。方法应用 td-1401a 干片式快速检测仪对献血者 alt 进行初筛。结果献血者 alt 初筛不合格中,男性显著高于女性P <0.01(χ2=110.840);不同年龄献血者,随年龄的增长不合格率显著上升P <0.01(χ2=280.110);不同职业、不同类型献血者有显著差异P <0.01(χ2=651.070,416.490);体重超标献血者是 alt 不合格的首要原因,P <0.01(χ2=764.390);生

  18. Successful immortalization of mesenchymal progenitor cells derived from human placenta and the differentiation abilities of immortalized cells

    International Nuclear Information System (INIS)

    We reported previously that mesenchymal progenitor cells derived from chorionic villi of the human placenta could differentiate into osteoblasts, adipocytes, and chondrocytes under proper induction conditions and that these cells should be useful for allogeneic regenerative medicine, including cartilage tissue engineering. However, similar to human mesenchymal stem cells (hMSCs), though these placental cells can be isolated easily, they are difficult to study in detail because of their limited life span in vitro. To overcome this problem, we attempted to prolong the life span of human placenta-derived mesenchymal cells (hPDMCs) by modifying hTERT and Bmi-1, and investigated whether these modified hPDMCs retained their differentiation capability and multipotency. Our results indicated that the combination of hTERT and Bmi-1 was highly efficient in prolonging the life span of hPDMCs with differentiation capability to osteogenic, adipogenic, and chondrogenic cells in vitro. Clonal cell lines with directional differentiation ability were established from the immortalized parental hPDMC/hTERT + Bmi-1. Interestingly, hPDMC/Bmi-1 showed extended proliferation after long-term growth arrest and telomerase was activated in the immortal hPDMC/Bmi-1 cells. However, the differentiation potential was lost in these cells. This study reports a method to extend the life span of hPDMCs with hTERT and Bmi-1 that should become a useful tool for the study of mesenchymal stem cells

  19. Annealing improves tribological property of poly(octadecene-alt-maleic anhydride) self-assembled film

    Energy Technology Data Exchange (ETDEWEB)

    Song Shiyong, E-mail: sysong0827@gmail.com [Pharmaceutic College of Henan University, Kaifeng 475004 (China); Liu Lei [Pharmaceutic College of Henan University, Kaifeng 475004 (China); Zhang Junyan [Pharmaceutic College of Henan University, Kaifeng 475004 (China); State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000 (China)

    2011-09-15

    A poly(octadecene-alt-maleic anhydride) (POMA) film was covalently immobilized on N-[3-(trimethoxylsilyl)propyl]ethylenediamine self-assembled monolayer modified silicon surface. Attenuated total reflectance Fourier transform infrared spectra were used to confirm the chemical bonding. Water contact angles and ellipsometric thicknesses were measured before and after annealing treatment. Atomic force microscopy was applied for top morphology, surface adhesion force and friction force. Anti-wear properties of the films were also evaluated on a ball-on-plate tribometer. It was found that annealing treatment which would evoke a conformation transform thermodynamically, was a critical step in the preparation of anti-wear films, especially for polymer ones. The correlation between structure and tribological property was revealed, which has profound meaning in designing excellent anti-wear nano-coatings used in microelectronic mechanical systems (MEMS).

  20. Detailed design specification for the ALT Shuttle Information Extraction Subsystem (SIES)

    Science.gov (United States)

    Clouette, G. L.; Fitzpatrick, W. N.

    1976-01-01

    The approach and landing test (ALT) shuttle information extraction system (SIES) is described in terms of general requirements and system characteristics output products and processing options, output products and data sources, and system data flow. The ALT SIES is a data reduction system designed to satisfy certain data processing requirements for the ALT phase of the space shuttle program. The specific ALT SIES data processing requirements are stated in the data reduction complex approach and landing test data processing requirements. In general, ALT SIES must produce time correlated data products as a result of standardized data reduction or special purpose analytical processes. The main characteristics of ALT SIES are: (1) the system operates in a batch (non-interactive) mode; (2) the processing is table driven; (3) it is data base oriented; (4) it has simple operating procedures; and (5) it requires a minimum of run time information.

  1. Prognostic relevance of ALT-associated markers in liposarcoma: a comparative analysis

    Directory of Open Access Journals (Sweden)

    Daidone MariaGrazia

    2010-06-01

    Full Text Available Abstract Background Most cancers maintain telomeres by activating telomerase but a significant minority, mainly of mesenchymal origin, utilize an alternative lengthening of telomeres (ALT mechanism. Methods In this study we comparatively analyzed the prognostic relevance of ALT in a monoinstitutional series of 85 liposarcoma patients as a function of the marker (ALT-associated promyelocytic leukemia bodies (APB versus heterogeneous telomeres used to classify the tumor. Results Independently of the detection approach, ALT proved to be a prognostic discriminant of increased mortality, although the prognostic relevance of the two markers appeared at different follow-up intervals (at 10 years for APB and 15 years for telomeres. Conclusions Overall, we confirmed ALT as an indicator of poor clinical outcome in this disease and provide the first evidence that the sensitivity of the ALT predictive power depends, at least in part, on the method used.

  2. Oxidative DNA damage correlates with cell immortalization and mir-92 expression in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    MicroRNAs expression has been extensively studied in hepatocellular carcinoma but little is known regarding the relationship, if any, with inflammation, production of reactive oxygen species (ROS), host’s repair mechanisms and cell immortalization. This study aimed at assessing the extent of oxidative DNA damage (8-hydroxydeoxyguanosine - 8-OHdG) in different phases of the carcinogenetic process, in relation to DNA repair gene polymorphism, telomeric dysfunction and to the expression of several microRNAs, non-coding genes involved in post-transcriptional regulation, cell proliferation, differentiation and death. Tissue samples obtained either at surgery, [neoplastic (HCC) and adjacent non-cancerous cirrhotic tissues (NCCT)] at percutaneous or laparoscopic biopsy (patients with HCV or HBV-related hepatitis or patients undergoing cholecystectomy) were analysed for 8-OHdG (HPLC-ED), OGG1 (a DNA repair gene) polymorphism (PCR-RFLP), telomerase activity, telomere length (T/S, by RT-PCR), Taqman microRNA assay and Bad/Bax mRNA (RT-PCR). Fifty-eight samples from 29 HCC patients (obtained in both neoplastic and peritumoral tissues), 22 from chronic hepatitis (CH) and 10 controls (cholecystectomy patients - CON) were examined. Eight-OHdG levels were significantly higher in HCC and NCCT than in CH and CON (p=0.001). Telomerase activity was significantly higher in HCC than in the remaining subgroups (p=0.002); conversely T/S was significantly lower in HCC (p=0.05). MiR-199a-b, -195, -122, -92a and −145 were down-regulated in the majority of HCCs while miR-222 was up-regulated. A positive correlation was observed among 8-OHdG levels, disease stage, telomerase activity, OGG1 polymorphisms and ALT/GGT levels. In HCC, miR-92 expression correlated positively with telomerase activity, 8-OHdG levels and Bad/Bax mRNA. The above findings confirm the accumulation, in the progression of chronic liver damage to HCC, of a ROS-mediated oxidative DNA damage, and suggest that this

  3. Oxidative DNA damage correlates with cell immortalization and mir-92 expression in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Romilda Cardin

    2012-05-01

    Full Text Available Abstract Background MicroRNAs expression has been extensively studied in hepatocellular carcinoma but little is known regarding the relationship, if any, with inflammation, production of reactive oxygen species (ROS, host’s repair mechanisms and cell immortalization. This study aimed at assessing the extent of oxidative DNA damage (8-hydroxydeoxyguanosine - 8-OHdG in different phases of the carcinogenetic process, in relation to DNA repair gene polymorphism, telomeric dysfunction and to the expression of several microRNAs, non-coding genes involved in post-transcriptional regulation, cell proliferation, differentiation and death. Methods Tissue samples obtained either at surgery, [neoplastic (HCC and adjacent non-cancerous cirrhotic tissues (NCCT] at percutaneous or laparoscopic biopsy (patients with HCV or HBV-related hepatitis or patients undergoing cholecystectomy were analysed for 8-OHdG (HPLC-ED, OGG1 (a DNA repair gene polymorphism (PCR-RFLP, telomerase activity, telomere length (T/S, by RT-PCR, Taqman microRNA assay and Bad/Bax mRNA (RT-PCR. Fifty-eight samples from 29 HCC patients (obtained in both neoplastic and peritumoral tissues, 22 from chronic hepatitis (CH and 10 controls (cholecystectomy patients - CON were examined. Results Eight-OHdG levels were significantly higher in HCC and NCCT than in CH and CON (p=0.001. Telomerase activity was significantly higher in HCC than in the remaining subgroups (p=0.002; conversely T/S was significantly lower in HCC (p=0.05. MiR-199a-b, -195, -122, -92a and −145 were down-regulated in the majority of HCCs while miR-222 was up-regulated. A positive correlation was observed among 8-OHdG levels, disease stage, telomerase activity, OGG1 polymorphisms and ALT/GGT levels. In HCC, miR-92 expression correlated positively with telomerase activity, 8-OHdG levels and Bad/Bax mRNA. Conclusions The above findings confirm the accumulation, in the progression of chronic liver damage to HCC, of a ROS

  4. Elevated Alt and Ast in an Asymptomatic Person: What the primary care doctor should do?

    OpenAIRE

    Yin, Loh Keng; Tong, Kew Siang

    2009-01-01

    Abnormal liver function test with raised alanine aminotransferase (ALT) and raised aspartate aminotransferase (AST) are commonly seen in primary care setting.Chronic alcohol consumption, drugs, non-alcoholic steatohepatitis (NASH) and chronic viral hepatitis are common causes associated with raised ALT and AST.In chronic viral hepatitis, the elevation of liver enzyme may not correlate well with the degree of liver damage.Non-hepatic causes of raised ALT and AST include polymyositis, acute mus...

  5. TEAM TEACHING IN JAPAN FROM THE PERSPECTIVES OF THE ALTs, THE JTEs, AND THE STUDENTS

    OpenAIRE

    Andrea Ann Johannes

    2012-01-01

    This case study explores team teaching in Japan from the perspectives of JTEs (Japanese English Teachers), ALTs (Assistant Language Teachers), and students. Special focus is attributed to teachers and students’ perceptions of ALT and JTE roles. To determine the perspectives of all three participants, 112 students, 4 JTES and 2 ALTs from a Japanese high school in Chiba Prefecture were surveyed. Fieldwork was conducted over a ten-day period at the research site in 2009 to collect data in the fo...

  6. Antioxidant and Antifatigue Activities of Polygonatum Alte-lobatum Hayata Rhizomes in Rats

    OpenAIRE

    Chi-Ting Horng; Jon-Kway Huang; Hui-Yun Wang; Chi-Chang Huang; Fu-An Chen

    2014-01-01

    Polygonatum alte-lobatum Hayata, a rhizomatous perennial herb, belongs to the Liliaceae family and is endemic to Taiwan. We investigated the antioxidant and anti-fatigue activities of P. alte-lobatum in exercised rats. Levels of polyphenols, flavonoids and polysaccharides and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging activity were measured in extracts of P. alte-lobatum (EPA). Sprague-Dawley rats were randomly divided into four groups for 8-week treatment with vehicle (con...

  7. Prognostic relevance of ALT-associated markers in liposarcoma: a comparative analysis

    OpenAIRE

    Daidone MariaGrazia; Gronchi Alessandro; Motta Rosita; Venturini Lorenza; Zaffaroni Nadia

    2010-01-01

    Abstract Background Most cancers maintain telomeres by activating telomerase but a significant minority, mainly of mesenchymal origin, utilize an alternative lengthening of telomeres (ALT) mechanism. Methods In this study we comparatively analyzed the prognostic relevance of ALT in a monoinstitutional series of 85 liposarcoma patients as a function of the marker (ALT-associated promyelocytic leukemia bodies (APB) versus heterogeneous telomeres) used to classify the tumor. Results Independentl...

  8. Production of the Allergenic Protein Alt a 1 by Alternaria Isolates from Working Environments

    OpenAIRE

    Justyna Skóra; Anna Otlewska; Beata Gutarowska; Joanna Leszczyńska; Iwona Majak; Łukasz Stępień

    2015-01-01

    The aim of the study was to evaluate the ability of Alternaria isolates from workplaces to produce Alt a 1 allergenic protein, and to analyze whether technical materials (cellulose, compost, leather) present within the working environment stimulate or inhibit Alt a 1 production (ELISA test). Studies included identification of the isolated molds by nucleotide sequences analyzing of the ITS1/ITS2 regions, actin, calmodulin and Alt a 1 genes. It has been shown that Alternaria molds are signific...

  9. Immortal objects: the objectification of women as terror management.

    Science.gov (United States)

    Goldenberg, Jamie L

    2013-01-01

    Philosophical theorizing, research on self-objectification, and the newest empirical research on the objectification of others converge to support the notion that the objectification of women entails rendering women, quite literally, as objects. This chapter begins with a review of this literature and then moves onto the question of why women are viewed as objects. The answer offered is informed by terror management theory, and suggests that the need to manage a fear of death creates a fundamental problem with the physical body, and such difficulties resonate especially in reaction to women's--menstruating, lactating, childbearing--bodies, and men's attraction to them. Evidence is presented to support this, and for the position that this situation plays a role in, not just expectations for women to be beautiful, but in the literal transformation of women into inanimate--immortal--objects. PMID:23947279

  10. Immortalized Rat Astrocyte Strain Genetically Modified by Rat Preprogalanin Gene

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To construct an immortalized rat astrocyte strain genetically modified by rat preprogalanin gene (IAST/GAL) and detect its galanin (GAL) expression and secretion, a cDNA fragment of rat GAL in plasmid of pBS KS(+)-GAL was inserted into eukaryotic expression vector pcDNA3.1(+) by DNA recombinant technology, then the restriction enzyme digestion and DNA sequencing were carried out to evaluate the recombinant. The pcDNA3.1 (+)-GAL and pcDNA3.1 (+) construct were transfected into immortalized rat astrocyte strain (IAST) by lipofectamine and the population of cells which stably integrated the construct was selected with 600 μg/mL G418. Individual clones were screened and expanded into clonal cell strains. Detection of Neo gene was used to validate the success of the transfection. Immunocytochemical staining, RT-PCR and radioimmunoassay were used to detect the expression and secretion level of GAL. The recombinant had been successfully constructed by restriction enzyme digestion and DNA sequencing. Detection of Neo gene showed that the pcDNA3.1 (+)-GAL and pcDNA3.1 (+) have been successfully transfected into IAST. After selection by using G418, IAST/GAL and IAST/Neo cell strains were obtained.IAST/GAL, IAST/Neo and IAST were immunostained positively for GAL, but the GAL average optical density of IAST/GAL was significantly higher than that of IAST/Neo and IAST (P<0.01). The level of GAL mRNA expression and the supernatant concentration of GAL in cultured IAST/GAL were significantly higher than those of IAST and IAST/Neo (P<0.01), but no significant differences were found between the IAST and IAST/Neo (P>0.05). It was concluded that IAST/GAL strain was constructed successfully and it might provide a basis for the further study of pain therapy.

  11. Establishment and culture optimization of a new type of pituitary immortalized cell line

    Energy Technology Data Exchange (ETDEWEB)

    Kokubu, Yuko [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Asashima, Makoto [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Life Science Center of TARA, The University of Tsukuba, Ibaraki-ken 305-8577 (Japan); Kurisaki, Akira, E-mail: akikuri@hotmail.com [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8562 (Japan)

    2015-08-07

    The pituitary gland is a center of the endocrine system that controls homeostasis in an organism by secreting various hormones. The glandular anterior pituitary consists of five different cell types, each expressing specific hormones. However, their regulation and the appropriate conditions for their in vitro culture are not well defined. Here, we report the immortalization of mouse pituitary cells by introducing TERT, E6, and E7 transgenes. The immortalized cell lines mainly expressed a thyrotroph-specific thyroid stimulating hormone beta (Tshb). After optimization of the culture conditions, these immortalized cells proliferated and maintained morphological characteristics similar to those of primary pituitary cells under sphere culture conditions in DMEM/F12 medium supplemented with N2, B27, basic FGF, and EGF. These cell lines responded to PKA or PKC pathway activators and induced the expression of Tshb mRNA. Moreover, transplantation of the immortalized cell line into subcutaneous regions and kidney capsules of mice further increased Tshb expression. These results suggest that immortalization of pituitary cells with TERT, E6, and E7 transgenes is a useful method for generating proliferating cells for the in vitro analysis of pituitary regulatory mechanisms. - Highlights: • Mouse pituitary cell lines were immortalized by introducing TERT, E6, and E7. • The immortalized cell lines mainly expressed thyroid stimulating hormone beta. • The cell lines responded to PKA or PKC pathway activators, and induced Tshb.

  12. Establishment and culture optimization of a new type of pituitary immortalized cell line

    International Nuclear Information System (INIS)

    The pituitary gland is a center of the endocrine system that controls homeostasis in an organism by secreting various hormones. The glandular anterior pituitary consists of five different cell types, each expressing specific hormones. However, their regulation and the appropriate conditions for their in vitro culture are not well defined. Here, we report the immortalization of mouse pituitary cells by introducing TERT, E6, and E7 transgenes. The immortalized cell lines mainly expressed a thyrotroph-specific thyroid stimulating hormone beta (Tshb). After optimization of the culture conditions, these immortalized cells proliferated and maintained morphological characteristics similar to those of primary pituitary cells under sphere culture conditions in DMEM/F12 medium supplemented with N2, B27, basic FGF, and EGF. These cell lines responded to PKA or PKC pathway activators and induced the expression of Tshb mRNA. Moreover, transplantation of the immortalized cell line into subcutaneous regions and kidney capsules of mice further increased Tshb expression. These results suggest that immortalization of pituitary cells with TERT, E6, and E7 transgenes is a useful method for generating proliferating cells for the in vitro analysis of pituitary regulatory mechanisms. - Highlights: • Mouse pituitary cell lines were immortalized by introducing TERT, E6, and E7. • The immortalized cell lines mainly expressed thyroid stimulating hormone beta. • The cell lines responded to PKA or PKC pathway activators, and induced Tshb

  13. Cytogenetic characterization and H-ras associated transformation of immortalized human mammary epithelial cells

    Directory of Open Access Journals (Sweden)

    Larivee Siobhan

    2006-05-01

    Full Text Available Abstract Introduction Immortalization is a key step in malignant transformation, but immortalization alone is insufficient for transformation. Human mammary epithelial cell (HMEC transformation is a complex process that requires additional genetic changes beyond immortalization and can be accomplished in vitro by accumulation of genetic changes and expression of H-ras. Methods HMEC were immortalized by serial passaging and transduction with the catalytic subunit of the human telomerase gene (hTERT. The immortalized cells were passaged in vitro and studied by a combination of G- banding and Spectral Karyotyping (SKY. H-ras transduced, hTERT immortalized cells were cloned in soft agar and injected into nude mice. Extensive analysis was performed on the tumors that developed in nude mice, including immunohistochemistry and western blotting. Results Immortal HMEC alone were not tumorigenic in γ-irradiated nude mice and could not grow in soft agar. Late passage hTERT immortalized HMEC from a donor transduced with a retroviral vector containing the mutant, autoactive, human H-ras61L gene acquired anchorage independent growth properties and the capacity for tumorigenic growth in vivo. The tumors that developed in the nude mice were poorly differentiated epithelial carcinomas that continued to overexpress ras. These cells were resistant to doxorubicin mediated G1/S phase arrest but were sensitive to treatment with a farnesyltransferase inhibitor. Conclusion Some of the cytogenetic changes are similar to what is observed in premalignant and malignant breast lesions. Despite these changes, late passage immortal HMEC are not tumorigenic and could only be transformed with overexpression of a mutant H-ras oncogene.

  14. Shift work aggravates metabolic syndrome development among early-middle-aged males with elevated ALT

    Institute of Scientific and Technical Information of China (English)

    Yu-Cheng Lin; Tun-Jen Hsiao; Pau-Chung Chen

    2009-01-01

    AIM: To examine whether shift work accelerates metabolic syndrome (MetS) development among early middle- aged males with elevated alanine aminotransferase (e-ALT).METHODS: A retrospective, observational followup study on MetS development at a 5-year interval was conducted using health examination data. Nine hundred and ninety six male employees not fulfilling MetS criteria at screening were enrolled. Age, MetScomponents,liver enzymes, serological markers for viral hepatitis, abdominal ultrasound, insulin resistance status, lifestyles, and workplace factors were analyzed.RESULTS: The prevalence of elevated serum ALT (> 40 U/L, e-ALT) at baseline was 19.1%. There were 381 (38.3%) workers with long-term exposures to daynight rotating shift work (RSW). 14.2% of subjects developed MetS during follow-up. After 5 years, the workers with e-ALT had significantly unfavorable changes in MetS-components, and higher rates of MetS development, vs subjects with normal baseline ALT levels. Workers with both baseline e-ALT and 5-year persistent RSW (pRSW) exposure had the highest rate of MetS development. Also, e-ALT-plus-pRSW workers had a significant increase in MetS-components at follow-up, compared with the other subgroups. After controlling for potential confounders, e-ALT-plus-pRSW workers posed a significant risk for MetS development (odds ratio, 2.7; 95% confidence interval, 1.4-5.3, vs workers without baseline e-ALT nor pRSW). CONCLUSION: We suggest that all early middleaged male employees with e-ALT should be evaluated and managed for MetS. Particularly in terms of job arrangements, impacts of long-term RSW on MetS development should be assessed for all male employees having baseline e-ALT.

  15. Preliminary design analysis of the ALT-II limiter for TEXTOR

    International Nuclear Information System (INIS)

    Installation of a large toroidal belt pump limiter, Advanced Limiter Test II (ALT-II), on the TEXTOR tokamak at Juelich, FRG is anticipated for early 1986. This paper discusses the preliminary mechanical design and materials considerations undertaken as part of the feasibility study phase for ALT-II

  16. Clinical significance of activity of ALT enzyme in patients with hepatitis C virus

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate serum alanine aminotransferase (ALT) levels in relation to the clinical, biochemical,ultrasonographic and histological characteristics of patients with hepatitis C virus.METHODS: Duration of disease, HCV-RNA, liver steatosis, and the hepatitis activity index (HAI) were correlated with serum ALT in 36 patients with HCV. ALT values were also investigated in 16 control subjects without any liver diseases.RESULTS: In bivariate analyses, ALT levels correlated with duration of HCV infection (P< 0.01), HCV-RNA (P<0.05), and the HAI(P<0.01). Among the components of the HAI, ALT concentrations were significantly associated with pedportal bridging/necrosis (P<0.01) and fibrosis (P<0.05). In multivariate analysis, periportal bridging/necrosis (β = 0.508; P < 0.01), duration of HCV infection (β = 0.413; P < 0.01), and HCV-RNA (β= 0.253; P < 0.05)were independently associated with ALT activity. The normal ALT activity for men and women was < 23 IU/L and < 22 IU/L, respectively.CONCLUSION: In patients with HCV, alterations in the liver tissue as reflected by ALT elevation are mainly associated with periportal bridging/necrosis, viral load and duration of disease. A cut-off value < 23 IU/L distinguished with high diagnostic accuracy healthy controls from patients with HCV.

  17. Switch telomerase to ALT mechanism by inducing telomeric DNA damages and dysfunction of ATRX and DAXX.

    Science.gov (United States)

    Hu, Yang; Shi, Guang; Zhang, Laichen; Li, Feng; Jiang, Yuanling; Jiang, Shuai; Ma, Wenbin; Zhao, Yong; Songyang, Zhou; Huang, Junjiu

    2016-01-01

    Activation of telomerase or alternative lengthening of telomeres (ALT) is necessary for tumours to escape from dysfunctional telomere-mediated senescence. Anti-telomerase drugs might be effective in suppressing tumour growth in approximately 85-90% of telomerase-positive cancer cells. However, there are still chances for these cells to bypass drug treatment after switching to the ALT mechanism to maintain their telomere integrity. But the mechanism underlying this switch is unknown. In this study, we used telomerase-positive cancer cells (HTC75) to discover the mechanism of the telomerase-ALT switch by inducing telomere-specific DNA damage, alpha-thalassemia X-linked syndrome protein (ATRX) knockdown and deletion of death associated protein (DAXX). Surprisingly, two important ALT hallmarks in the ALT-like HTC75 cells were observed after treatments: ALT-associated promyelocytic leukaemia bodies (APBs) and extrachromosomal circular DNA of telomeric repeats. Moreover, knocking out hTERT by utilizing the CRISPR/Cas9 technique led to telomere elongation in a telomerase-independent manner in ALT-like HTC75 cells. In summary, this is the first report to show that inducing telomeric DNA damage, disrupting the ATRX/DAXX complex and inhibiting telomerase activity in telomerase-positive cancer cells lead to the ALT switch. PMID:27578458

  18. Specific chromosomal imbalances in human papillomavirus-transfected cells during progression toward immortality

    OpenAIRE

    Solinas-Toldo, Sabina; Dürst, Matthias; Lichter, Peter

    1997-01-01

    High risk human papillomaviruses (HPVs) known to be closely associated with cervical cancer, such as HPV16 and HPV18, have the potential to immortalize human epithelial cells in culture. Four lines of HPV-transfected keratinocytes were analyzed by comparative genomic hybridization at different time points after transfection. A number of chromosomal imbalances was found to be highly characteristic for the cultures progressing toward immortality. Whereas several of these were new and previously...

  19. Immortalized human hepatic cell lines for in vitro testing and research purposes

    OpenAIRE

    Ramboer, Eva; Vanhaecke, Tamara; Rogiers, Vera; Vinken, Mathieu

    2015-01-01

    The ubiquitous shortage of primary human hepatocytes has urged the scientific community to search for alternative cell sources, such as immortalized hepatic cell lines. Over the years, several human hepatic cell lines have been produced, whether or not using a combination of viral oncogenes and human telomerase reverse transcriptase protein. Conditional approaches for hepatocyte immortalization have also been established and allow generation of growth-controlled cell lines. A variety of immor...

  20. Spontaneous Immortalization of Clinically Normal Colon-Derived Fibroblasts from a Familial Adenomatous Polyposis Patient

    Directory of Open Access Journals (Sweden)

    Nicholas R. Forsyth

    2004-05-01

    Full Text Available Normal human diploid cells do not spontaneously immortalize in culture, but instead enter replicative senescence after a finite number of population doublings. Ablation of key checkpoint arrest or cancersuppressor genes, through dominantly inherited germline mutation (p53+/-, Li-Fraumeni or viral oncogene expression (SV40 large T, HPV16/18, E6/E7 can lead to escape from senescence, additional doublings, entrance into crisis phase, where immortal clones emerge at low frequency. In the vast majority of cases, telomerase is reactivated and telomeres are stabilized. Here we describe the spontaneous immortalization of clinically normal fibroblasts derived from colonic stroma of a familial adenomatous polyposis (FAP patient. The preimmortal (C26C and the spontaneously immortalized derivative (C26Ci cells are heterozygous for a characterized germline mutation in exon 15 of the adenomatous polyposis coli gene. Immortalization was accompanied by spontaneous reactivation of endogenous telomerase and establishment of telomeres at presenescent lengths. Normal checkpoint behavior is retained and a diploid karyotype is maintained. These cells provide a valuable new addition to the limited number of spontaneously immortalized human cell types, particularly fibroblast cells, will be useful in experimentally determining the functional pathways in neoplastic development and in the identification of potential molecular targets for cancer chemoprevention.

  1. The Quest for Immortality: Science at the Frontiers of Aging

    Energy Technology Data Exchange (ETDEWEB)

    Olshansky, S. Jay (University of Illinois at Chicago); Carnes, Bruce A. (University of Chicago)

    2001-10-24

    For more than a decade, Dr. Olshansky and Dr. Carnes have been working in the field of aging to identify the biological attributes of species that influence their length of life. Amid countless claims by scientists and the lay population that human life expectancy will continue to rise indefinitely in the future, Olshansky and Carnes have stood fast in their conviction that such claims are without any scientific basis. In their book The Quest for Immortality, S. Jay Olshansky and Bruce A. Carnes provide a comprehensive account of the real science of aging, from a historical overview of religious and philosophical thinking about aging and death, to the biology behind the changes we see in the mirror, to the promising but frightening future of genetic engineering. They demystify the complex language and concepts of science, explain how to distinguish real science from media hype in order to help readers make informed health decisions, and offer a powerfully optimistic vision of aging and health in the twenty-first century.

  2. Expectations of immortality: dam safety management into the next millennium

    International Nuclear Information System (INIS)

    Topics concerning the problems associated with older and aging dams are considered including: what can be done to extent the lifetime of an old dam, the decision to decommission a dam based on a value judgment that the risk of maintaining the dam is too great for society's acceptance, the possibility of change in the level of risk tolerance with time in a technological environment, traditional surveillance methods used by dam owners in the Y2K situation, and the unreality of dam immortality. Trends and means for preserving older dams for their owner's purposes are outlined, as well as their lifetime compared to that of the downstream systems they serve. Despite the fact that we live in a throwaway society, dam owners cannot just leave their dam asset when they are through with using it. Someone has to maintain the dam, or ensure that it is safely decommissioned when the owner is finished with it. On a worldwide scale the available pool of experienced dam engineers is shrinking. This problem needs to be addressed by a shift towards operating and dam safety management skills based on a firm awareness of dam design principles. A shift in society's expectations has occurred such that dam designers and owners must now recognize the impact a dam can have both on its natural and social environments. Because of the increasing emphasis on paying attention to the impacts of people's activities on the planet, engineers more than anyone else must have a significant influence in that direction. 9 refs

  3. Some features of alt texts associated with images in Web pages

    Directory of Open Access Journals (Sweden)

    Timothy C. Craven

    2006-01-01

    Full Text Available Introduction. This paper extends a series on summaries of Web objects, in this case, the alt attribute of image files. Method. Data were logged from 1894 pages from Yahoo!'s random page service and 4703 pages from the Google directory; an img tag was extracted randomly from each where present; its alt attribute, if any, was recorded; and the header for the corresponding image file was retrieved if possible. Analysis. Associations were measured between image type and use of null alt values, image type and image file size, image file size and alt text length, and alt text length and number of images on the page. Results. 16.6% and 17.3% of pages respectively showed no img elements. Of 1579 and 3888 img tags randomly selected from the remainder, 47.7% and 49.4% had alt texts, of which 26.3% and 27.5% were null. Of the 1316 and 3384 images for which headers could be retrieved, 71.2% and 74.2% were GIF, 28.1% and 20.5%, JPEG; and 0.8% and 0.8% PNG. GIF images were more commonly assigned null alt texts than JPEG images, and GIF files tended to be shorter than JPEG files. Weak positive correlations were observed between image file size and alt text length, except for JPEG files in the Yahoo! set. Alt texts for images from pages containing more images tended to be slightly shorter. Conclusion. Possible explanations for the results include GIF files' being more suited to decorative images and the likelihood that many images on image-rich pages are content-poor.

  4. Loss of p53 protein in human papillomavirus type 16 E6-immortalized human mammary epithelial cells.

    OpenAIRE

    Band, V; De Caprio, J A; Delmolino, L; Kulesa, V; Sager, R

    1991-01-01

    We have shown previously that introduction of the human papillomavirus type 16 (HPV16) or HPV18 genome into human mammary epithelial cells induces their immortalization. These immortalized cells have reduced growth factor requirements. We report here that transfection with a single HPV16 gene E6 is sufficient to immortalize these cells and reduce their growth factor requirements. The RB protein is normal in these cells, but the p53 protein is sharply reduced, as shown by immunoprecipitation w...

  5. RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells

    OpenAIRE

    Arora, Rajika; Lee, Yongwoo; Wischnewski, Harry; Brun, Catherine M.; Schwarz, Tobias; Azzalin, Claus M.

    2014-01-01

    A fraction of cancer cells maintain telomeres through the telomerase-independent, ‘Alternative Lengthening of Telomeres’ (ALT) pathway. ALT relies on homologous recombination (HR) between telomeric sequences; yet, what makes ALT telomeres recombinogenic remains unclear. Here we show that the RNA endonuclease RNaseH1 regulates the levels of RNA–DNA hybrids between telomeric DNA and the long noncoding RNA TERRA, and is a key mediator of telomere maintenance in ALT cells. RNaseH1 associated to t...

  6. The telomere-associated homeobox-containing protein TAH1/HMBOX1 participates in telomere maintenance in ALT cells

    OpenAIRE

    Feng, Xuyang; Luo, Zhenhua; Jiang, Shuai; Li, Feng; Han, Xin; Hu, Yang; Wang, Dan; Zhao, Yong; Ma, Wenbin; Liu, Dan; Huang, Junjiu; Songyang, Zhou

    2013-01-01

    The majority of cancer cells rely on elevated telomerase expression and activity for rapid growth and proliferation. Telomerase-negative cancer cells, by contrast, often employ the alternative lengthening of telomeres (ALT) pathway to maintain telomeres. ALT cells are characterized by long and dynamic telomeres and the presence of ALT-associated promyelocytic leukemia (PML) bodies (APBs). Previous work has shown the importance of APBs to the ALT pathway, but their formation and precise role r...

  7. Expectations of immortality: dam safety management into the next millennium

    Energy Technology Data Exchange (ETDEWEB)

    Palmer, M.D. [Tonkin and Taylor International Ltd., Auckland, (New Zealand)

    1999-07-01

    Topics concerning the problems associated with older and aging dams are considered including: what can be done to extent the lifetime of an old dam, the decision to decommission a dam based on a value judgment that the risk of maintaining the dam is too great for society's acceptance, the possibility of change in the level of risk tolerance with time in a technological environment, traditional surveillance methods used by dam owners in the Y2K situation, and the unreality of dam immortality. Trends and means for preserving older dams for their owner's purposes are outlined, as well as their lifetime compared to that of the downstream systems they serve. Despite the fact that we live in a throwaway society, dam owners cannot just leave their dam asset when they are through with using it. Someone has to maintain the dam, or ensure that it is safely decommissioned when the owner is finished with it. On a worldwide scale the available pool of experienced dam engineers is shrinking. This problem needs to be addressed by a shift towards operating and dam safety management skills based on a firm awareness of dam design principles. A shift in society's expectations has occurred such that dam designers and owners must now recognize the impact a dam can have both on its natural and social environments. Because of the increasing emphasis on paying attention to the impacts of people's activities on the planet, engineers more than anyone else must have a significant influence in that direction. 9 refs.

  8. Detection of quantitative trait loci and heterotic loci for plant height using an immortalized F2 population in maize

    Institute of Scientific and Technical Information of China (English)

    TANG JiHua; MA XiQing; TENG WenTao; YAN JianBing; WU WeiRen; DAI JingRui; LI JianSheng

    2007-01-01

    A set of recombinant inbred lines (RIL) derived from Yuyu22, an elite hybrid widespread in China, was used to construct an immortalized F2 (IF2) population comprising 441 different crosses. Genetic linkage maps were constructed containing 10 linkages groups with 263 simple sequence repeat (SSR) molecular markers. Twelve and ten quantitative trait loci (QTL) were detected for plant height in the IF2 and RIL populations respectively, using the composite interval mapping method, and six same QTL were identified in the two populations. In addition, ten unique heterotic loci (HL) located on seven different chromosomes were revealed for plant height using the mid-parent heterosis as the input data. These HL explained 1.26%-8.41% of the genotypic variance in plant height heterosis and most expressed overdominant effects. Only three QTL and HL were located in the same chromosomal region, it implied that plant height and its heterosis might be controlled by two types of genetic mechanisms.

  9. Alte Harfe. Vollständige Sammlung alter estnischer Volkslieder : Vorrede / Jakob Hurt

    Index Scriptorium Estoniae

    Hurt, Jakob, 1839-1907

    2005-01-01

    Eessõna rmt. : Hurt, Jakob. Vana kannel. 1. kogu : täieline kogu vanu eesti rahvalaulusid = Alte Harfe : vollständige Sammlung alter estnischen Volkslieder. Tartu, 1875-1886. - (Eesti Kirjameeste Seltsi toimetised ; 3)

  10. Conditionally immortalized human pancreatic stellate cell lines demonstrate enhanced proliferation and migration in response to IGF-I

    Energy Technology Data Exchange (ETDEWEB)

    Rosendahl, Ann H., E-mail: ann.rosendahl@med.lu.se [Lund University, Department of Clinical Sciences Lund, Division of Surgery, Lund (Sweden); Lund University and Skåne University Hospital, Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund (Sweden); Gundewar, Chinmay; Said Hilmersson, Katarzyna [Lund University, Department of Clinical Sciences Lund, Division of Surgery, Lund (Sweden); Ni, Lan; Saleem, Moin A. [University of Bristol, School of Clinical Sciences, Children' s Renal Unit and Academic Renal Unit, Bristol (United Kingdom); Andersson, Roland [Lund University, Department of Clinical Sciences Lund, Division of Surgery, Lund (Sweden)

    2015-01-15

    Pancreatic stellate cells (PSCs) play a key role in the dense desmoplastic stroma associated with pancreatic ductal adenocarcinoma. Studies on human PSCs have been minimal due to difficulty in maintaining primary PSC in culture. We have generated the first conditionally immortalized human non-tumor (NPSC) and tumor-derived (TPSC) pancreatic stellate cells via transformation with the temperature-sensitive SV40 large T antigen and human telomerase (hTERT). These cells proliferate at 33°C. After transfer to 37°C, the SV40LT is switched off and the cells regain their primary PSC phenotype and growth characteristics. NPSC contained cytoplasmic vitamin A-storing lipid droplets, while both NPSC and TPSC expressed the characteristic markers αSMA, vimentin, desmin and GFAP. Proteome array analysis revealed that of the 55 evaluated proteins, 27 (49%) were upregulated ≥3-fold in TPSC compared to NPSC, including uPA, pentraxin-3, endoglin and endothelin-1. Two insulin-like growth factor binding proteins (IGFBPs) were inversely expressed. Although discordant IGFBP-2 and IGFBP-3 levels, IGF-I was found to stimulate proliferation of both NPSC and TPSC. Both basal and IGF-I stimulated motility was significantly enhanced in TPSC compared to NPSC. In conclusion, these cells provide a unique resource that will facilitate further study of the active stroma compartment associated with pancreatic cancer. - Highlights: • Generation of human conditionally immortalized human pancreatic stellate cell lines. • Temperature-sensitive SV40LT allows switch to primary PSC phenotype characteristics. • Proteome profiling revealed distinct expression patterns between TPSC and NPSC. • Enhanced IGF-I-stimulated proliferation and motility by TPSC compared to NPSC.

  11. Differential Evolutionary Selection and Natural Evolvability Observed in ALT Proteins of Human Filarial Parasites.

    Directory of Open Access Journals (Sweden)

    Neil C Devoe

    Full Text Available The abundant larval transcript (ALT-2 protein is present in all members of the Filarioidea, and has been reported as a potential candidate antigen for a subunit vaccine against lymphatic filariasis. To assess the potential for vaccine escape or heterologous protection, we examined the evolutionary selection acting on ALT-2. The ratios of nonsynonymous (K(a to synonymous (K(s mutation frequencies (ω were calculated for the alt-2 genes of the lymphatic filariasis agents Brugia malayi and Wuchereria bancrofti and the agents of river blindness and African eyeworm disease Onchocerca volvulus and Loa loa. Two distinct Bayesian models of sequence evolution showed that ALT-2 of W. bancrofti and L. loa were under significant (P<0.05; P < 0.001 diversifying selection, while ALT-2 of B. malayi and O. volvulus were under neutral to stabilizing selection. Diversifying selection as measured by ω values was notably strongest on the region of ALT-2 encoding the signal peptide of L. loa and was elevated in the variable acidic domain of L. loa and W. bancrofti. Phylogenetic analysis indicated that the ALT-2 consensus sequences formed three clades: the first consisting of B. malayi, the second consisting of W. bancrofti, and the third containing both O. volvulus and L. loa. ALT-2 selection was therefore not predictable by phylogeny or pathology, as the two species parasitizing the eye were selected differently, as were the two species parasitizing the lymphatic system. The most immunogenic regions of L. loa and W. bancrofti ALT-2 sequence as modeled by antigenicity prediction analysis did not correspond with elevated levels of diversifying selection, and were not selected differently than predicted antigenic epitopes in B. malayi and O. volvulus. Measurements of ALT-2 evolvability made by χ2 analysis between alleles that were stable (O. volvulus and B. malayi and those that were under diversifying selection (W. bancrofti and L. loa indicated significant (P<0

  12. Reversible Immortalization Enables Seamless Transdifferentiation of Primary Fibroblasts into Other Lineage Cells.

    Science.gov (United States)

    Xie, Fei; Gong, Kerui; Li, Ke; Zhang, Mingliang; Chang, Judy C; Jiang, Shizhong; Ye, Lin; Wang, Jiaming; Tan, Yuting; Kan, Yuet Wai

    2016-08-15

    Fibroblasts can be transdifferentiated directly into other somatic cells such as cardiomyocytes, hematopoietic cells, and neurons. An advantage of somatic cell differentiation without first generating induced pluripotent stem cells (iPSCs) is that it avoids contamination of the differentiated cells with residual iPSCs, which may cause teratoma. However, since primary fibroblasts from biopsy undergo senescence during repeated culture, it may be difficult to grow transdifferentiated cells in sufficient numbers for future therapeutic purposes. To circumvent this problem, we reversibly immortalized primary fibroblasts by using the piggyBac transposon to deliver the human telomerase reverse transcriptase (hTERT) gene hTERT plus SV40 Large T. Both approaches enabled fibroblasts to grow continuously without senescence, and neither caused teratoma formation in immunodeficient mice. However, fibroblasts immortalized with hTERT plus SV40 large T antigen accumulated chromosomal rearrangements, whereas fibroblasts immortalized with hTERT retained the normal karyotype. To transdifferentiate hTERT-immortalized fibroblasts into other somatic lineage cells, we transiently transfected them with episomal OCT4 and cultured them under neural cell growth condition with transposase to remove the transposon. Tripotent neural progenitor cells were seamlessly and efficiently generated. Thus, reversible immortalization of primary fibroblasts with hTERT will allow potential autologous cell-based therapeutics that bypass and simulate iPSC generation. PMID:27328768

  13. Alternative lengthening of telomeres (ALT) in cancer stem cells in vivo

    OpenAIRE

    Bojovic, Bojana; Booth, Ryan E.; Jin, Yi; Zhou, Xiaofeng; Crowe, David L.

    2014-01-01

    Chromosome ends are protected by telomeres which prevent DNA damage response and degradation. Telomerase expression extends telomeres and inhibits DNA damage response. Telomeres are also maintained by the recombination based alternative lengthening pathway. Telomerase is believed to be the sole mechanism for telomere maintenance in epidermis. We show that basal cells in epidermis maintain telomeres both by telomerase and ALT mechanisms in vivo. ALT was detected in epidermal stem cells in Terc...

  14. RECOMBINANT PROTEIN PRODUCTION OF ABUNDANT LARVAL TRANSCRIPT (ALT-2 IN ESCHERICHIA COLI

    Directory of Open Access Journals (Sweden)

    Kamran Ashraf

    2013-02-01

    Full Text Available Lymphatic filariasis is a major tropical disease caused by mosquito born nematodes Brugia malayi and Wuchereria bancrofti. Vaccine against filariasis must generate immunity to infective mosquito derived L3 stage. Two highly expressed genes designated abundant larval transcript-1 and -2 (alt-1 and alt-2. ALT-1 and ALT-2 represent closely related protein (79% it. Now, expression of this alt gene in E. coli BL21plysS for the production of vaccine is major challenge as no vaccine is available against this disease. Work was carried out to express this protein at laboratory scale bioreactor. At first optimization of different parameter like suitability of media, inducer concentration, induction time was done for getting maximum amount of recombinant protein. In shake flask studies, after induction (max cell density and max specific growth rate stage good expression of ALT-2 protein was found. However, at laboratory scale production done in bioreactor, expression level drastically decreased. Plasmid stability analysis was done in reactor and was found to be cause for decreased productivity. The stability was improved by increasing antibiotic concentration in the medium and also by pulsing antibiotic during induction. This led to better plasmid stability and increased expression levels in reactor similar to expression levels in shake flask studies.

  15. Construction and identification of immortalized rat astrocyte cell line expressing enkephalin

    Institute of Scientific and Technical Information of China (English)

    XU Ying; TIAN Yu-ke; TIAN Xue-bi; AN Ke; YANG Hui

    2007-01-01

    Objective: To provide a sound cell source for further ex-vivo gene therapy for chronic pain, we attempt to develop an immortalized rat astrocyte cell line that expresses enkephalin regulated by doxycycline.Methods: Retrovirus infection method was employed to develop an immortalized rat astrocyte cell line that could express enkephalin regulated by doxycycline. The hPPE gene expression level of immoralized astroyte cells (IAC)/hPPE was detected by RT-PCR, indirect immunofiuorescence staining and radioimmunoassay.Results: IAC carrying Tet-on system transfected with preproenkephalin gene could secrete enkephalin that was regulated by doxycycline in a dose-dependent manner and hPPE gene activation could be repeated in on-off-on cycles through administration or removal of doxycycline.Conclusion: An immortalized rat astrocyte cell line that secrete enkephalin under the control of doxycycline is established successfully, which provides a research basis for transgenic cell transplantation for analgesia.

  16. Differential Evolutionary Selection and Natural Evolvability Observed in ALT Proteins of Human Filarial Parasites.

    Science.gov (United States)

    Devoe, Neil C; Corbett, Ian J; Barker, Linsey; Chang, Robert; Gudis, Polyxeni; Mullen, Nathan; Perez, Kailey; Raposo, Hugo; Scholz, John; May, Meghan

    2016-01-01

    The abundant larval transcript (ALT-2) protein is present in all members of the Filarioidea, and has been reported as a potential candidate antigen for a subunit vaccine against lymphatic filariasis. To assess the potential for vaccine escape or heterologous protection, we examined the evolutionary selection acting on ALT-2. The ratios of nonsynonymous (K(a)) to synonymous (K(s)) mutation frequencies (ω) were calculated for the alt-2 genes of the lymphatic filariasis agents Brugia malayi and Wuchereria bancrofti and the agents of river blindness and African eyeworm disease Onchocerca volvulus and Loa loa. Two distinct Bayesian models of sequence evolution showed that ALT-2 of W. bancrofti and L. loa were under significant (Pvolvulus were under neutral to stabilizing selection. Diversifying selection as measured by ω values was notably strongest on the region of ALT-2 encoding the signal peptide of L. loa and was elevated in the variable acidic domain of L. loa and W. bancrofti. Phylogenetic analysis indicated that the ALT-2 consensus sequences formed three clades: the first consisting of B. malayi, the second consisting of W. bancrofti, and the third containing both O. volvulus and L. loa. ALT-2 selection was therefore not predictable by phylogeny or pathology, as the two species parasitizing the eye were selected differently, as were the two species parasitizing the lymphatic system. The most immunogenic regions of L. loa and W. bancrofti ALT-2 sequence as modeled by antigenicity prediction analysis did not correspond with elevated levels of diversifying selection, and were not selected differently than predicted antigenic epitopes in B. malayi and O. volvulus. Measurements of ALT-2 evolvability made by χ2 analysis between alleles that were stable (O. volvulus and B. malayi) and those that were under diversifying selection (W. bancrofti and L. loa) indicated significant (P<0.01) deviations from a normal distribution for both W. bancrofti and L. loa. The

  17. H-ras expression in immortalized keratinocytes produces an invasive epithelium in cultured skin equivalents.

    Directory of Open Access Journals (Sweden)

    Melville B Vaughan

    Full Text Available BACKGROUND: Ras proteins affect both proliferation and expression of collagen-degrading enzymes, two important processes in cancer progression. Normal skin architecture is dependent both on the coordinated proliferation and stratification of keratinocytes, as well as the maintenance of a collagen-rich basement membrane. In the present studies we sought to determine whether expression of H-ras in skin keratinocytes would affect these parameters during the establishment and maintenance of an in vitro skin equivalent. METHODOLOGY/PRINCIPAL FINDINGS: Previously described cdk4 and hTERT immortalized foreskin keratinocytes were engineered to express ectopically introduced H-ras. Skin equivalents, composed of normal fibroblast-contracted collagen gels overlaid with keratinocytes (immortal or immortal expressing H-ras, were prepared and incubated for 3 weeks. Harvested tissues were processed and sectioned for histology and antibody staining. Antigens specific to differentiation (involucrin, keratin-14, p63, basement-membrane formation (collagen IV, laminin-5, and epithelial to mesenchymal transition (EMT; e-cadherin, vimentin were studied. Results showed that H-ras keratinocytes produced an invasive, disorganized epithelium most apparent in the lower strata while immortalized keratinocytes fully stratified without invasive properties. The superficial strata retained morphologically normal characteristics. Vimentin and p63 co-localization increased with H-ras overexpression, similar to basal wound-healing keratinocytes. In contrast, the cdk4 and hTERT immortalized keratinocytes differentiated similarly to normal unimmortalized keratinocytes. CONCLUSIONS/SIGNIFICANCE: The use of isogenic derivatives of stable immortalized keratinocytes with specified genetic alterations may be helpful in developing more robust in vitro models of cancer progression.

  18. Porcine hepatocyte isolation and reversible immortalization mediated by retroviral transfer and site-specific recombination

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To develop a hepatocyte cell line, we immortalized primary porcine hepatocytes with a retroviral vector SSR#69 containing the Simian Virus 40 T antigen (SV40T ag). METHODS: We first established a method of porcine hepatocyte isolation with a modified four-step retrograde perfusion technique. Then the porcine hepatocytes were immortalized with retroviral vector SSR#69 expressing SV40T and hygromycin-resistance genes flanked by paired loxP recombination targets. SV40T cDNA in the expanded cells was subse...

  19. Understanding and Avoiding Immortal-Time Bias in Gastrointestinal Observational Research.

    Science.gov (United States)

    Targownik, Laura E; Suissa, Samy

    2015-12-01

    Pharmacoepidemiologic analyses, in which observational data is interrogated to evaluate relationships between patterns of drug use and both beneficial and adverse outcomes, are being increasingly used in the study of inflammatory bowel disease. However, the results of many of these analyses may be corrupted by the presence of immortal person-time bias, an analytic error which can result in an overestimation of the benefits of medical therapy. In this report, we will describe immortal person-time bias, explain the mechanism through which it confers a false benefit, and guide the reader in how to identify this source of bias in the medical literature.

  20. C60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages

    Science.gov (United States)

    Russ, K. A.; Elvati, P.; Parsonage, T. L.; Dews, A.; Jarvis, J. A.; Ray, M.; Schneider, B.; Smith, P. J. S.; Williamson, P. T. F.; Violi, A.; Philbert, M. A.

    2016-02-01

    There continues to be a significant increase in the number and complexity of hydrophobic nanomaterials that are engineered for a variety of commercial purposes making human exposure a significant health concern. This study uses a combination of biophysical, biochemical and computational methods to probe potential mechanisms for uptake of C60 nanoparticles into various compartments of living immune cells. Cultures of RAW 264.7 immortalized murine macrophage were used as a canonical model of immune-competent cells that are likely to provide the first line of defense following inhalation. Modes of entry studied were endocytosis/pinocytosis and passive permeation of cellular membranes. The evidence suggests marginal uptake of C60 clusters is achieved through endocytosis/pinocytosis, and that passive diffusion into membranes provides a significant source of biologically-available nanomaterial. Computational modeling of both a single molecule and a small cluster of fullerenes predicts that low concentrations of fullerenes enter the membrane individually and produce limited perturbation; however, at higher concentrations the clusters in the membrane causes deformation of the membrane. These findings are bolstered by nuclear magnetic resonance (NMR) of model membranes that reveal deformation of the cell membrane upon exposure to high concentrations of fullerenes. The atomistic and NMR models fail to explain escape of the particle out of biological membranes, but are limited to idealized systems that do not completely recapitulate the complexity of cell membranes. The surprising contribution of passive modes of cellular entry provides new avenues for toxicological research that go beyond the pharmacological inhibition of bulk transport systems such as pinocytosis.There continues to be a significant increase in the number and complexity of hydrophobic nanomaterials that are engineered for a variety of commercial purposes making human exposure a significant health concern

  1. Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells.

    Directory of Open Access Journals (Sweden)

    Sandra N Schlick

    Full Text Available Epstein-Barr virus (EBV is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III. The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15, is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator.

  2. Analysis of the survivability of the shuttle (ALT) fault-tolerant avionics system

    Science.gov (United States)

    1976-01-01

    An extension of the Complementary-Analytic-Simulative Technique (CAST) is presented which is applicable to the Shuttle Data Processing Subsystem (DPS). A two step process was used. The first step provides models, both analytic and simulative, for analysis of the Approach-Landing Test (ALT) configuration. The ALT modeling and analysis are presented. Since CAST had already been shown to be multicomputer systems, the emphasis was placed on extending the CAST concept so it is applicable to computer systems including the multiplicity of input and output devices found in a real-time control system application. The DPS mission-critical survivability for a six-hour mission was determined to be 0.999863 for the Shuttle ALT baseline configuration. Thus it can be said that for ALT, the survivability is adequate. However, the fact that orbiting missions of up to 30 days are planned illustrates the necessity of extending the ALT work to be applicable to OFT and actual mission scenarios. The above analysis led to the evaluation of three selected options which identified two areas of possible improvement. These improvements would result from use of a recovery technique which combines roll ahead with memory copy, and increased TACAN fault detectability.

  3. A preclinical mouse model of glioma with an alternative mechanism of telomere maintenance (ALT).

    Science.gov (United States)

    Jeitany, Maya; Pineda, Jose Ramon; Liu, Qingyuan; Porreca, Rosa Maria; Hoffschir, Françoise; Desmaze, Chantal; Silvestre, David C; Mailliet, Patrick; Junier, Marie-Pierre; Londoño-Vallejo, Arturo; Ségal-Bendirdjian, Evelyne; Chneiweiss, Hervé; Boussin, François D

    2015-04-01

    Glioblastoma multiforme is the most aggressive primary tumor of the central nervous system. Glioma stem cells (GSCs), a small population of tumor cells with stem-like properties, are supposedly responsible for glioblastoma multiforme relapse after current therapies. In approximately thirty percent of glioblastoma multiforme tumors, telomeres are not maintained by telomerase but through an alternative mechanism, termed alternative lengthening of telomere (ALT), suggesting potential interest in developing specific therapeutic strategies. However, no preclinical model of ALT glioma was available until the isolation of TG20 cells from a human ALT glioma. Herein, we show that TG20 cells exhibit a high level of telomeric recombination but a stable karyotype, indicating that their telomeres retain their protective function against chromosomal instability. TG20 cells possess all of the characteristic features of GSCs: the expression of neural stem cell markers, the generation of intracerebral tumors in NOD-SCID-IL2Rγ (NSG) mice as well as in nude mice, and the ability to sustain serial intracerebral transplantations without expressing telomerase, demonstrating the stability of the ALT phenotype in vivo. Furthermore, we also demonstrate that 360B, a G-quadruplex ligand of the pyridine derivative series that impairs telomere replication and mitotic progression in cancer cells, prevents the development of TG20 tumors. Together, our results show that intracerebral grafts of TG20 cells in immunodeficient mice constitute an efficient preclinical model of ALT glioblastoma multiforme and that G-quadruplex ligands are a potential therapy for this specific type of tumor. PMID:25175359

  4. Analysis on Motion and Cable Dynamic Tension for An ALT-Tanker System

    Institute of Scientific and Technical Information of China (English)

    LI Hong-xia; TANG You-gang; LIU Li-qin; ZHANG Ruo-yu

    2009-01-01

    A two-degree freedom model for an ALT-tanker system is established corresponding to the pitch of the ALT and the surge of the tanker.Tension in the mooring cable between the ALT and the tanker is represented by an unsymmetrical,piecewise-nonlinear function.Wave load on the tower is evaluated by use of the Morison equation.The first order wave load acting on the tanker is calculated by the linear diffraction theory based on the 2-D Helmholtz equation,and the near field approach of Pinkster is used to evaluate the second order drift force.The dynamic equation of motion is established based on the principle of D'lembert.Dynamic response and cable tension of a mooring system composed of an 88.4 m ALT and a 100000 t grade tanker are calculated.The influence of wave frequency,wave excitation amplitude,wind and current force on ALT-tanker motion and cable tension is discussed.

  5. Bilinçaltı Reklamlar ve Bilinçaltı Reklamlarda Cinsellik Öğesinin Kullanılması

    OpenAIRE

    Acet, Duygu

    2013-01-01

    Reklam; günlük hayatta insanların çok karşılaştıkları bir tutundurma bileşenidir. Bir ürün reklam sayesinde tanınır. Tüketici ürünü reklam sonrası satın almaya karar verir. Reklam da, tüketicide bu satın alma davranışını gerçekleştirebilmek için çeşitli taktiklere başvurur. Bu taktikler; bazen mizah, ünlü kullanımı gibi tüketiciye zarar vermeyen tarzda, bazen de bilinçaltı reklamlar gibi tüketiciyi olumsuz yönde etkileyebilecek şekilde uygulanabilir. Tezin amacı, bilinçaltı reklamlarda k...

  6. Telomere extension by telomerase and ALT generates variant repeats by mechanistically distinct processes

    OpenAIRE

    Lee, Michael; Hills, Mark; Conomos, Dimitri; Stutz, Michael D.; Dagg, Rebecca A.; Lau, Loretta M. S.; Reddel, Roger R; Hilda A Pickett

    2013-01-01

    Telomeres are terminal repetitive DNA sequences on chromosomes, and are considered to comprise almost exclusively hexameric TTAGGG repeats. We have evaluated telomere sequence content in human cells using whole-genome sequencing followed by telomere read extraction in a panel of mortal cell strains and immortal cell lines. We identified a wide range of telomere variant repeats in human cells, and found evidence that variant repeats are generated by mechanistically distinct processes during te...

  7. Immortality of Prejudice in Striving Ubuntu: Case Studies of Community Managed Schools in Nepal

    Science.gov (United States)

    Rajbhandari, Mani Man Singh; Rajbhandari, Smriti

    2016-01-01

    The immortality of prejudice after the school management transfer has not been judged. This makes communities to take responsibility for schools further by compelling the government to mandate amendments of Community Managed Schools (CMS) Directives. The purpose was to explore the CMS enduring Ubuntu against immorality of prejudice, through…

  8. Functionally Charged Polystyrene Particles Activate Immortalized Mouse Microglia (BV2): Cellular and Genomic Response

    Science.gov (United States)

    The effect of particle surface charge on the biological activation of immortalized mouse microglia (BV2) was examined. Same size (~850-950 nm) spherical polystyrene microparticles (SPM) with net negative (carboxyl, COOH-) or positive (dimethyl amino, CH3)2

  9. Tissue distribution and engraftment of human mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene

    DEFF Research Database (Denmark)

    Bentzon, J F; Stenderup, K; Hansen, F D;

    2005-01-01

    Engraftment of mesenchymal stem cells (MSC) in peripheral tissues for replenishing of local stem cell function has been proposed as a therapeutic approach to degenerative diseases. We have previously reported the development of an immortalized human telomerase reverse transcriptase transduced MSC...

  10. Development of a full-thickness human gingiva equivalent constructed from immortalized keratinocytes and fibroblasts

    NARCIS (Netherlands)

    J.K. Buskermolen; C.M.A. Reijnders; S.W. Spiekstra; T. Steinberg; C.J. Kleverlaan; A.J. Feilzer; A.D. Bakker; S. Gibbs

    2016-01-01

    Organotypic models make it possible to investigate the unique properties of oral mucosa in vitro. For gingiva, the use of human primary keratinocytes (KC) and fibroblasts (Fib) is limited due to the availability and size of donor biopsies. The use of physiologically relevant immortalized cell lines

  11. Characterization of lipid metabolism in insulin-sensitive adipocytes differentiated from immortalized human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Prawitt, Janne; Niemeier, Andreas; Kassem, Moustapha;

    2008-01-01

    There is a great demand for cell models to study human adipocyte function. Here we describe the adipogenic differentiation of a telomerase-immortalized human mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of terminally differentiated adipocytes even after prolonged...

  12. Precise conditional immortalization of mouse cells using tetracycline-regulated SV40 large T-antigen.

    Science.gov (United States)

    Anastassiadis, Konstantinos; Rostovskaya, Maria; Lubitz, Sandra; Weidlich, Stefanie; Stewart, A Francis

    2010-04-01

    Cellular immortalization provides a way for expansion and subsequent molecular characterization of rare cell types. Ideally, immortalization can be achieved by the reversible expression of immortalizing proteins. Here, we describe the use of conditional immortalization based on a modified tetracycline-regulated system for the expression of SV40 large T-antigen in embryonic stem (ES) cells and mice. The modified system relies on a codon improved reverse tetracycline transactivator (irtTA) fused to the ligand-binding domain (LBD) of the androgen receptor (irtTA-ABD) or of a mutated glucocorticoid receptor (irtTA-GBD*). Induction of T-antigen is conferred only after addition of two ligands, one to activate the LBD (mibolerone for irtTA-ABD or dexamethasone for irtTA-GBD*) and one to activate the tetracycline transactivator (doxycycline). In ES cells, changes in gene expression upon large T induction were limited and reversible upon deinduction. Similarly, expression of T-antigen was very tightly regulated in mice. We have isolated and expanded bone marrow mesenchymal stem cells that could be genetically manipulated and maintained their differentiation properties after several passages of expansion under conditions that induce the expression of large T-antigen. PMID:20146354

  13. Grafting amino drugs to poly(styrene-alt-maleic anhydride) as a potential method for drug release

    Energy Technology Data Exchange (ETDEWEB)

    Khazaei, Ardeshir; Saednia, Shahnaz; Saien, Javad; Abbasi, Fatemeh, E-mail: Khazaei_1326@yahoo.com, E-mail: ssaednia@gmail.com [Faculty of Chemistry, Bu-Ali Sina University, Hamedan (Iran, Islamic Republic of); Kazem-Rostami, Masoud [Young Researchers Club and Elite, Takestan Branch, Islamic Azad University, Takestan (Iran, Islamic Republic of); Sadeghpour, Mahdieh [Department of Chemistry, Takestan Branch, Islamic Azad University, Takestan (Iran, Islamic Republic of); Borazjani, Maryam Kiani [Faculty of Science, Department of Chemistry, Bushehr Payame Noor University (PNU), Bushehr (Iran, Islamic Republic of)

    2013-07-15

    Drug delivery systems based on polymer-drug conjugates give an improved treatment with lower toxicity or side effects and be used for the treatment of different diseases. Conjugates of biodegradable poly(styrene-alt-maleic anhydride) (PSMA), with a therapeutic agents such as amantadine hydrochloride, amlodipine, gabapentin, zonisamide and mesalamine, were afforded by the formation of the amide bonds of the amino drugs that reacted with the PSMA anhydride groups. The amounts of covalently conjugated drugs were determined by a {sup 1}H NMR spectroscopic method, and the in vitro release rate in buffer solution (pH 1.3) was studied at body temperature 37 Degree-Sign C. In kinetic studies, different dissolution models were examined to obtain drug release data and the collected data were well-fitted to the Korsmeyer-Peppas equation, revealing a dominant Fickian diffusion mechanism for drug release under the in vitro conditions. (author)

  14. $A_{LT}$ in the polarized Drell-Yan process at RHIC and HERA energies

    CERN Document Server

    Kanazawa, Y; Nishiyama, N; Koike, Yuji

    1998-01-01

    We present a leading order (LO) estimate for the longitidinal-transverse spin asymmetry (A_{LT}) in the nucleon-nucleon polarized Drell-Yan process at RHIC and HERA-$\\vec{N}$ energies in comparison with A_{LL} and A_{TT}. A_{LT} receives contribution from g_1, the transversity ditribution h_1, and the twist-3 distributions g_T and h_L. For the twist-3 contribution we use the bag model prediction evolved to high Q^2 by the large-N_c evolution equation. We found that A_{LT} (normalized by the asymmetry in the parton level) is much smaller than the corresponding A_{TT}. Twist-3 contribution given by the bag model also turned out to be negligible.

  15. $A_{LT}$ in the Nucleon-Nucleon Polarized Drell-Yan Process

    CERN Document Server

    Kanazawa, Y; Nishiyama, N; Koike, Yuji

    2000-01-01

    We present a leading order (LO) estimate for the longitidinal-transverse spin asymmetry (A_{LT}) in the nucleon-nucleon polarized Drell-Yan process at RHIC and HERA-$\\vec{N}$ energies in comparison with A_{LL} and A_{TT}. A_{LT} receives contribution from g_1, the transversity ditribution h_1, and the twist-3 distributions g_T and h_L. For the twist-3 contribution we use the bag model prediction evolved to a high energy scale by the large-N_c evolution equation. We found that A_{LT} (normalized by the asymmetry in the parton level) is much smaller than the corresponding A_{TT}. Twist-3 contribution given by the bag model also turned out to be negligible.

  16. Camera Mouse Including “Ctrl-Alt-Del” Key Operation Using Gaze, Blink, and Mouth Shape

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2013-04-01

    Full Text Available This paper presents camera mouse system with additional feature: "CTRL - ALT - DEL" key. The previous gaze-based camera mouse systems are only considering how to obtain gaze and making selection. We proposed gaze-based camera mouse with "CTRL - ALT - DEL" key. Infrared camera is put on top of display while user looking ahead. User gaze is estimated based on eye gaze and head pose. Blinking and mouth detections are used to create "CTR - ALT - DEL" key. Pupil knowledge is used to improve robustness of eye gaze estimation against different users. Also, Gabor filter is used to extract face features. Skin color information and face features are used to estimate head pose. The experiments of each method have done and the results show that all methods work perfectly. By implemented this system, troubleshooting of camera mouse can be done by user itself and makes camera mouse be more sophisticated.

  17. National blood requirement, serum ALT and hepatitis in Ethiopian blood donors.

    Science.gov (United States)

    Zawde, D; Sisay, Y

    1991-10-01

    To appraise the national blood requirement and supply, and to determine the impact of alanine aminotransferase (ALT) and hepatitis B surface antigen (HBsAg) screening on the blood supply, 407 random blood donor sera were tested for HBsAg, human immunodeficiency virus (HIV), and ALT activity. HBsAg and anti-HIV antibody were determined by the enzyme linked immunosorbent assay (ELISA) technique using Hepanostica and Welcozyme kits, respectively. The Western Blot test was performed to confirm anti-HIV positive sera by the ELISA technique. ALT was determined by an automated photometer using ALAT kits and serologic testing for syphilis was done by the rapid plasma reagin (RPR) test. The amount of blood required in Ethiopia and the actual supply was calculated on the basis of the number and type of hospital beds in Addis Abeba and the amount of blood transfusions in units per hospital bed. The results showed that the combined donor and unit rejection rate was 34.6%. The annual blood requirement was 7 units for emergency and 4 units for nonemergency beds. The national blood requirement in 1989 was 64,350-80,000 units, but the supply met only a third of the requirement. The mean and 2SD cut off ALT levels were 28 and 69 IU/L, respectively. ALT was elevated in 9.1% of HBsAg positive but apparently healthy donors, while HBsAg screening eliminated 25% of those with elevated ALT activity. This data suggests that there is a serious blood shortage in Ethiopia and that the currently supplied blood is relatively unsafe in terms of hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1659534

  18. THE IDEA OF IMMORTALITY IN THE THEOCENTRICAL IDEOLOGICAL SYSTEMS AND IN A RELIGIOUS WORLDVIEW

    Directory of Open Access Journals (Sweden)

    Ekaterina Vadimovna Shiryaeva

    2015-01-01

    Full Text Available The article addresses the idea of human immortality, reflected in different ways in different forms of religious outlook, analyzes cultural, historical and individualpersonal traits of the existence of this idea. It is proved that individual- personal characteristics of the subject of religious consciousness have crucial significance for the predominance of soft or rigid forms of retribution beyond the grave. The article makes comparison of Christianity, Islam and Buddhism and Western and Orthodox versions of immortality within the Christian religion. Detailed attention is paid to the ideas of the immortality in Russian philosophy (the heritage of N.F. Fedorov, N.A.Berdyaev, S.L. Frank, Lev Shestov.It is concluded that the moral reasons for rejecting the death by Russian thinkers are in their special attention to the value of the bodily-spiritual unity of the human personality.It is stated that two main social functions performed by religion as a social institution are repressive and compensatory functions; the latter exist and interact as a dialectical contradiction. The author considers the typical approaches to the problem of death and immortality by Orthodox theologians of the 19th and 20th centuries; it is noted that in their works there is a tendency towards decreasing the repressive component in the models of the underworld retribution. At the same time, the disciplinary function of the official church religiosity is important, as the church retains its influence mainly through the implementation of this function.It is concluded that the perceptions of the human postmortem existence reflect the national-cultural and subjective-personal features of understanding the justice as an ethical category, as well as the fact that the idea of immortality in religious consciousness takes different forms not only in accordance with the type of religion but rather with the type of personal attitude to the problem of death.

  19. The People Paradox: Self-Esteem Striving, Immortality Ideologies, and Human Response to Climate Change

    Directory of Open Access Journals (Sweden)

    Janis L. Dickinson

    2009-06-01

    Full Text Available In 1973, Ernest Becker, a cultural anthropologist cross-trained in philosophy, sociology, and psychiatry, invoked consciousness of self and the inevitability of death as the primary sources of human anxiety and repression. He proposed that the psychological basis of cooperation, competition, and emotional and mental health is a tendency to hold tightly to anxiety-buffering cultural world views or “immortality projects” that serve as the basis for self-esteem and meaning. Although he focused mainly on social and political outcomes like war, torture, and genocide, he was increasingly aware that materialism, denial of nature, and immortality-striving efforts to control, rather than sanctify, the natural world were problems whose severity was increasing. In this paper I review Becker’s ideas and suggest ways in which they illuminate human response to global climate change. Because immortality projects range from belief in technology and materialism to reverence for nature or belief in a celestial god, they act both as barriers to and facilitators of sustainable practices. I propose that Becker's cross-disciplinary “science of man,” and the predictions it generates for proximate-level determinants of social behavior, add significantly to our understanding of and potential for managing the people paradox, i.e., that the very things that bring us symbolic immortality often conflict with our prospects for survival. Analysis of immortality projects as one of the proximate barriers to addressing climate change is both cautionary and hopeful, providing insights that should be included in the cross-disciplinary quest to uncover new pathways toward rational, social change.

  20. Immortalization of porcine placental trophoblast cells through reconstitution of telomerase activity.

    Science.gov (United States)

    Zhang, Hongling; Huang, Yong; Wang, Lili; Yu, Tingting; Wang, Zengguo; Chang, Lingling; Zhao, Xiaomin; Luo, Xiaomao; Zhang, Liang; Tong, Dewen

    2016-05-01

    Placental trophoblast cells (PTCs) play a critical role in histotrophic nutrient absorption, gaseous exchange, endocrine activities, and barrier function between the maternal and fetal systems. Establishment of immortalized porcine PTCs will help us to investigate the potential effects of different viruses on porcine trophoblast. In the present study, primary porcine PTCs were isolated from healthy gilts at Day 30 to Day 50 of gestation through collagenase digestion, percoll gradient centrifugation, and anti-CD9 immunomagnetic negative selection. To provide stable and long lifespan cells, primary PTCs were transfected with human telomerase reverse transcriptase (hTERT) gene. One porcine placental trophoblast cell line, named as hTERT-PTCs, was chosen for characterization. Human telomerase reverse transcriptase-PTCs achieved an extended replicative lifespan without exhibiting any neoplastic transformation signs in vivo or in vitro. The morphologic and key physiological characteristics of the immortalized PTCs were similar to primary PTCs. The immortalized PTCs retained original cell polarity and normal karyotype, expressed trophoblast-specific marker cytokeratin 7 and E-cadherin but did not express vimentin and major histocompatibility complex class I antigens as well as primary PTCs. Human telomerase reverse transcriptase-PTCs secreted low levels of chorionic gonadotrophin β-subunit and placental lactogen that were coincident with primary PTCs. Taken together, our results demonstrated that the porcine PTCs could be immortalized through reconstitution of telomerase activity. The immortalized PTCs maintained its original characteristics and can be used as a model cells line to study the pathologic changes of porcine placental trophoblast in viruses infectious diseases. PMID:26850465

  1. Ephedra alte (Joint Pine): An Invasive, Problematic Weedy Species in Forestry and Fruit Tree Orchards in Jordan

    OpenAIRE

    Qasem, Jamal R.

    2012-01-01

    A field survey was carried out to record plant species climbed by Ephedra alte in certain parts of Jordan during 2008–2010. Forty species of shrubs, ornamental, fruit, and forest trees belonging to 24 plant families suffered from the climbing habit of E. alte. Growth of host plants was adversely affected by E. alte growth that extended over their vegetation. In addition to its possible competition for water and nutrients, the extensive growth it forms over host species prevents photosynthesis...

  2. Keeping It in the Family: ATRX Loss Promotes Persistent Sister Telomere Cohesion in ALT Cancer Cells.

    Science.gov (United States)

    Roake, Caitlin M; Artandi, Steven E

    2015-09-14

    In this issue of Cancer Cell, Ramamoorthy and Smith report that cancer cells that maintain their chromosome ends through alternative lengthening of telomeres (ALT) display persistent sister telomere cohesion. This delayed resolution of sister telomere cohesion depends upon the loss of ATRX and its histone-sequestering function and is associated with increased recombination between sister telomeres. PMID:26373274

  3. ALT-C 2004 Organisational Isues: Moving towards learning networks for lifelong learning

    NARCIS (Netherlands)

    Koper, Rob

    2004-01-01

    Invited address (16/4/2004) at the ALT-C 2004 conference: "Blue skies and pragmatism - learning technologies for the next decade". Exeter, Devon, England, between 14/9/2004 and 16/9/2004. The address was positioned in the Organisational Theme. It presents some currents organisational problems as the

  4. Influence of gender, BMI, and ethnicity on serum ALT levels of healthy students of a medical school

    International Nuclear Information System (INIS)

    Background: Alanine Aminotransferase (ALT) is an enzyme found in Liver and indicates injury to Hepatocytes. It is influenced by various factors. The objectives of this study were to identify the correlates of ALT activity among healthy medical students of Army Medical College, National University of Sciences and Technology, aged 18-22 years. This was to establish the mean ALT levels of the students and compare them with those in various parts of the world and observe various correlations that exist and factors that may influence ALT levels. Methods: This population included 143 volunteer students (93 men and 50 women) selected on the basis of negative answers to a detailed medical questionnaire including past medical history, drug and alcohol consumption, on the absence of clinical signs of liver disease, on the negativity of serological testing for Hepatitis B and C virus. Results: The mean ALT level of the entire population was 28.7 IU/L. A major sex-difference in ALT value was observed, the mean ALT value being higher in men than in women (32.1+- 21.7 vs. 22.6 +- 9.7 IU/L, p<0.004). According to WHO criteria for Asians, normal BMI was taken from 18.5-23.0 Kg/m/sup 2/. There was a positive significant correlation between serum ALT level and BMI (p<0.002). ALT level strongly correlates with body mass index and gender. There was no significant variation in ALT levels among Punjabis and Sindhis, Balochis, Pathans, and Kashmiris. Conclusion: We suggest the need of taking into account these parameters in a clinical interpretation of ALT level. (author)

  5. Phenotype transformation of immortalized NCM460 colon epithelial cell line by TGF-β1 is associated with chromosome instability.

    Science.gov (United States)

    Huang, Chao; Wen, Bin

    2016-10-01

    Transforming growth factor-β1 (TGF-β1) within tumor microenvironment has a pivotal function in cancer initiation and tumorigenesis, and hence this study was to observe the malignant transformation induced by TGF-β1 in an immortalized colon epithelial cell line NCM460 for better understanding the mechanisms of colon carcinogenesis. Immortalized colon epithelial cell line NCM460 was used as the model of this study, and was treated with different concentrations of TGF-β1 for different time. Then, immunofluorescence was performed to observe the change of phenotype hallmarks including adherent junction protein E-cadherin, cytoskeleton protein vimentin, and tight junction marker ZO-1, western blotting analysis was performed to detect the expression of the above three markers and two transcription factors (Snail and Slug) involved in the transformation by TGF-β1. In addition, chromosome instability (CHI) including analysis of DNA-ploid was detected by flow cytometry. Our results revealed significant loss or reduction of ZO-1 and E-cadherin, and robust emergence of vimentin in the cell line NCM460 after a 15-, 20-, and 25-day treatment with 10 ng/ml TGF-β1. Interestingly, 20 and 25 days after stimulation with 5 ng/ml TGF-β1, expression of E-cadherin and ZO-1 revealed a pattern roughly similar to that of 10 ng/ml TGF-β1, especially, both expressions was vanished and vimentin expression was dramatically increased at days 25 after TGF-β1 stimulation. After a stimulation with 10 ng/ml TGF-β1 for 15, 20, and 25 days, the levels of Snail and Slug expression in the cells were significantly up-regulated, compared with the cells treated with TGF-β1 inhibitor LY364947, PBS or balnk control (P TGF-β1 after its stimulation for 15, 20, and 25 days. Very few mitotic cells with treatment of PBS for 15, 20 and 25 days were non-diploid whose DNA content was greater or less than 4 N, but these cells were significantly increased after exposure to TGF-β1 for 15, 20, and

  6. Immortalization of human foreskin keratinocytes by various human papillomavirus DNAs corresponds to their association with cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Woodworth, C.D.; Doniger, J.; DiPaolo, J.A.

    1989-01-01

    Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of cervical carcinoma.

  7. Milk as a symbol of immortality in the “Orphic” gold tablets from Thurii and Pelinna

    Directory of Open Access Journals (Sweden)

    Stian Sundell Torjussen

    2014-11-01

    Full Text Available This article offers an interpretation of the enigmatic “kid-in-milk” formula which appears in four of the “Orphic” gold tablets from Thurii and Pelinna. These tiny tablets accompanied the dead in their graves and contained texts of various lengths which were believed to help the deceased on his or her journey to the otherworld. Many see the tablets as Orphic texts, but this question has been highly debated during the last century. The four tablets in question, from two sites in southern Italy and Greece, tell how the deceased has suffered in life, but that he or she has attained immortality through initiation. The immortalization was referred to and summed up in the “kid-in-milk” formula, where, it is argued, milk was a direct reference to immortality. Thus milk in this eschatological context is a symbol of immortality which served as a focal point for both the text and the initates.

  8. Immortalization of human foreskin keratinocytes by various human papillomavirus DNAs corresponds to their association with cervical carcinoma

    International Nuclear Information System (INIS)

    Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of cervical carcinoma

  9. “不朽”之探析——解读昆德拉小说《不朽》%Explore the "Immortality" --Interpret the Kaunda's novel The Immortal"

    Institute of Scientific and Technical Information of China (English)

    张东旭

    2012-01-01

    In human existence, the immortal has many of possibility, Kaunda's Novels Immortal, he focuses on asking this question. The theme, with the intertwining of modern "immortal" and the historical mortal. so a lot of people began to question and discuss it. In Milan novel take the different individuals" attitude for immortal as a 'immortal", let the reader explore the true meaning of the immortal.%不朽在人类的生存境况中,有着无数种的可能性,因此便有了人们对不朽可能性的追问与意义的探究。而米兰·昆德拉的小说《不朽》正集中追问了这个问题。小说以不同个体对"不朽"的态度为主题,将现代语境下的"不朽"与历史意义上的"不朽"相交织,让读者去探寻不朽的真实含义。

  10. Establishment of an Immortalized Skin Keratinocyte Cell Line Derived from the Animal Model Mastomys coucha

    Science.gov (United States)

    Hasche, Daniel; Stephan, Sonja; Savelyeva, Larissa; Westermann, Frank; Rösl, Frank

    2016-01-01

    In the present report we describe the establishment of a spontaneous immortalized skin keratinocyte cell line derived from the skin of the multimammate rodent Mastomys coucha. These animals are used in preclinical studies for a variety of human diseases such as infections with nematodes, bacteria and papillomaviruses, especially regarding cutaneous manifestations such as non-melanoma skin cancer. Here we characterize the cells in terms of their origin and cytogenetic features. Searching for genomic signatures, a spontaneous mutation in the splicing donor sequence of Trp53 (G to A transition at the first position of intron 7) could be detected. This point mutation leads to alternative splicing and to a premature stop codon, resulting in a truncated and, in turn, undetectable form of p53, probably contributing to the process of immortalization. Mastomys coucha-derived skin keratinocytes can be used as an in vitro system to investigate molecular and immunological aspects of infectious agent interactions with their host cells. PMID:27533138

  11. Mutational analysis of the activator of late transcription, Alt , in the lactococcal bacteriophage TP901-1

    DEFF Research Database (Denmark)

    Pedersen, Margit; Hammer, Karin

    2007-01-01

    An activator protein, Alt, synthesized during the early state of lytic infection is required for transcription of the late operon in the lactococcal phage TP901-1. In order to identify amino acid residues in the Alt protein required for activation of the TP901-1 late promoter, Plate, hydroxylamin...

  12. OBSERVATION OF MOVEMENTS DURING SLEEP IN ALTE (APPARENT LIFE-THREATENING EVENT) AND APNEIC INFANTS - A PILOT-STUDY

    NARCIS (Netherlands)

    EINSPIELER, C; PRECHTL, HFR; VANEYKERN, L; DEROOS, B

    1994-01-01

    Fourteen infants of 2 months or 6 months of age were video-recorded during polysomnography. Four were normal infants, five had a history of ALTE (apparent life threatening event) and five had repeated and prolonged apnoea during sleep. Two ALTE infants have been recorded at 2 months as well as at 6

  13. Association between ALT level and the rate of cardio/cerebrovascular events in HIV-positive individuals

    DEFF Research Database (Denmark)

    Sabin, Caroline A; Ryom, Lene; Kovari, Helen;

    2013-01-01

    An inverse association between serum alanine aminotransferase (ALT) levels and the risk of myocardial infarction (MI) has been reported in the general population. We investigated associations between ALT levels and the risk of various cardiovascular and cerebrovascular outcomes in a large cohort...

  14. William Gaddis’s Immortality: Celebration, Cartoon, or Corruption?

    OpenAIRE

    Crystal Alberts

    2013-01-01

    Although ostensibly a review of 'The Letters of William Gaddis' edited by Steven Moore (Champaign: Dalkey Archive, 2013), this article evaluates Moore’s volume in light of generally accepted practices of scholarly editions and the handling of historical documents. In particular, Alberts compares some of Moore’s edited letters to the originals housed either at Washington University in St. Louis or the Harry Ransom Center at the University of Texas, Austin and reveals issues involving the repre...

  15. A Grand Challenge: Immortal Information and Through-Life Knowledge Management (KIM)

    OpenAIRE

    Alexander Ball; Manjula Patel; Chris McMahon; Stuart Green; John Clarkson; Steve Culley

    2006-01-01

    Immortal information and through-life knowledge management: strategies and tools for the emerging product-service business paradigm’, is a Grand Challenge project involving eleven different UK universities and incorporating substantial industry collaboration. It is investigating a range of issues associated with the move towards a product-service paradigm in the engineering sector, in particular the long-term curation of digital data, learning from production and use, and appropriate governa...

  16. THE IDEA OF IMMORTALITY IN THE THEOCENTRICAL IDEOLOGICAL SYSTEMS AND IN A RELIGIOUS WORLDVIEW

    OpenAIRE

    Ekaterina Vadimovna Shiryaeva

    2015-01-01

    The article addresses the idea of human immortality, reflected in different ways in different forms of religious outlook, analyzes cultural, historical and individualpersonal traits of the existence of this idea. It is proved that individual- personal characteristics of the subject of religious consciousness have crucial significance for the predominance of soft or rigid forms of retribution beyond the grave. The article makes comparison of Christianity, Islam and Buddhism and Western and Ort...

  17. Ancestors in Borneo Societies. Death, Transformation and Social Immortality, Pascal Couderc & Kenneth Sillander, ed.

    Directory of Open Access Journals (Sweden)

    Antonio Guerreiro

    2013-06-01

    Full Text Available The volume Ancestors in Borneo Societies, edited by P. Couderc and K. Sillander assembles a series of ethnographically grounded studies. This book, stemming for a panel organized at the 8th Borneo Research Council Biennal Conference in Kuching, Sarawak (July 2006, adresses important questions relating to the ancestor cult and generally the conceptualization of ancestry on the island. As the subtitle to the book indicates (Death, Transformation and Social Immortality, the contributions explo...

  18. The People Paradox: Self-Esteem Striving, Immortality Ideologies, and Human Response to Climate Change

    OpenAIRE

    Janis L Dickinson

    2009-01-01

    In 1973, Ernest Becker, a cultural anthropologist cross-trained in philosophy, sociology, and psychiatry, invoked consciousness of self and the inevitability of death as the primary sources of human anxiety and repression. He proposed that the psychological basis of cooperation, competition, and emotional and mental health is a tendency to hold tightly to anxiety-buffering cultural world views or “immortality projects” that serve as the basis for self-esteem and meaning. Although ...

  19. Ancestors in Borneo Societies. Death, Transformation and Social Immortality, Pascal Couderc & Kenneth Sillander, ed.

    OpenAIRE

    Antonio Guerreiro

    2013-01-01

    The volume Ancestors in Borneo Societies, edited by P. Couderc and K. Sillander assembles a series of ethnographically grounded studies. This book, stemming for a panel organized at the 8th Borneo Research Council Biennal Conference in Kuching, Sarawak (July 2006), adresses important questions relating to the ancestor cult and generally the conceptualization of ancestry on the island. As the subtitle to the book indicates (Death, Transformation and Social Immortality), the contributions explo...

  20. Immortalized Human Schwann Cell Lines Derived From Tumors of Schwannomatosis Patients.

    Science.gov (United States)

    Ostrow, Kimberly Laskie; Donaldson, Katelyn; Blakeley, Jaishri; Belzberg, Allan; Hoke, Ahmet

    2015-01-01

    Schwannomatosis, a rare form of neurofibromatosis, is characterized predominantly by multiple, often painful, schwannomas throughout the peripheral nervous system. The current standard of care for schwannomatosis is surgical resection. A major obstacle to schwannomatosis research is the lack of robust tumor cell lines. There is a great need for mechanistic and drug discovery studies of schwannomatosis, yet appropriate tools are not currently available. Schwannomatosis tumors are difficult to grow in culture as they survive only a few passages before senescence. Our lab has extensive experience in establishing primary and immortalized human Schwann cell cultures from normal tissue that retain their phenotypes after immortalization. Therefore we took on the challenge of creating immortalized human Schwann cell lines derived from tumors from schwannomatosis patients. We have established and fully characterized 2 schwannomatosis cell lines from 2 separate patients using SV40 virus large T antigen. One patient reported pain and the other did not. The schwannomatosis cell lines were stained with S100B antibodies to confirm Schwann cell identity. The schwannomatosis cells also expressed the Schwann cell markers, p75NTR, S100B, and NGF after multiple passages. Cell morphology was retained following multiple passaging and freeze/ thaw cycles. Gene expression microarray analysis was used to compare the cell lines with their respective parent tumors. No differences in key genes were detected, with the exception that several cell cycle regulators were upregulated in the schwannomatosis cell lines when compared to their parent tumors. This upregulation was apparently a product of cell culturing, as the schwannomatosis cells exhibited the same expression pattern of cell cycle regulatory genes as normal primary human Schwann cells. Cell growth was also similar between normal primary and immortalized tumor cells in culture. Accurate cell lines derived directly from human tumors

  1. Immortalized Human Schwann Cell Lines Derived From Tumors of Schwannomatosis Patients.

    Directory of Open Access Journals (Sweden)

    Kimberly Laskie Ostrow

    Full Text Available Schwannomatosis, a rare form of neurofibromatosis, is characterized predominantly by multiple, often painful, schwannomas throughout the peripheral nervous system. The current standard of care for schwannomatosis is surgical resection. A major obstacle to schwannomatosis research is the lack of robust tumor cell lines. There is a great need for mechanistic and drug discovery studies of schwannomatosis, yet appropriate tools are not currently available. Schwannomatosis tumors are difficult to grow in culture as they survive only a few passages before senescence. Our lab has extensive experience in establishing primary and immortalized human Schwann cell cultures from normal tissue that retain their phenotypes after immortalization. Therefore we took on the challenge of creating immortalized human Schwann cell lines derived from tumors from schwannomatosis patients. We have established and fully characterized 2 schwannomatosis cell lines from 2 separate patients using SV40 virus large T antigen. One patient reported pain and the other did not. The schwannomatosis cell lines were stained with S100B antibodies to confirm Schwann cell identity. The schwannomatosis cells also expressed the Schwann cell markers, p75NTR, S100B, and NGF after multiple passages. Cell morphology was retained following multiple passaging and freeze/ thaw cycles. Gene expression microarray analysis was used to compare the cell lines with their respective parent tumors. No differences in key genes were detected, with the exception that several cell cycle regulators were upregulated in the schwannomatosis cell lines when compared to their parent tumors. This upregulation was apparently a product of cell culturing, as the schwannomatosis cells exhibited the same expression pattern of cell cycle regulatory genes as normal primary human Schwann cells. Cell growth was also similar between normal primary and immortalized tumor cells in culture. Accurate cell lines derived directly

  2. “Because I could not stop for Death-”:Belief in Immortality

    Institute of Scientific and Technical Information of China (English)

    袁飞

    2015-01-01

    One of the everlasting themes in poetry writing is “death”, with which Emily Dickinson is also obsessed in her careful observation and contemplation of life. This paper attempts to analyze one of her death poems: “Because I could not stop for Death-”. It shows the poet’s reflection on the inevitable fate of al living creatures in the universe and her firm belief in immortality thereafter.

  3. A Grand Challenge: Immortal Information and Through-Life Knowledge Management (KIM

    Directory of Open Access Journals (Sweden)

    Alexander Ball

    2006-11-01

    Full Text Available ‘Immortal information and through-life knowledge management: strategies and tools for the emerging product-service business paradigm’, is a Grand Challenge project involving eleven different UK universities and incorporating substantial industry collaboration. It is investigating a range of issues associated with the move towards a product-service paradigm in the engineering sector, in particular the long-term curation of digital data, learning from production and use, and appropriate governance and management techniques.

  4. Telomere and telomerase in the initial stage of immortalization of esophageal epithelial cell

    Institute of Scientific and Technical Information of China (English)

    Zhong-Ying Shen; Li-Yan Xu; En-Min Li; Wei-Jia Cai; Min-Hua Chen; Jian Shen; Yi Zeng

    2002-01-01

    AIM: To search for the biomarker of cellular immortalization,the telomere length, telomerase activity and its subunits incultured epithelial cells of human fetal esophagus in theprocess of immortalization.METHODS: The transgenic cell line of human fetalesophageal epithelium (SHEE) was established with E6 E7genes of bt man papillomavirus (HPV) type 18 in ourlaboratory. Morphological phenotype of cultured SHEE cellsfrom the 6th to 30th passages, was examined by phasecontrast microscopy, the telomere length was assayed bySouthern blot method, and the activity of telomerase wasanalyzed by telomeric repeat amplification protocol (TRAP).Expressions of subunits of telomerase, hTR and hTERT,were assessed by RT-PCR. DNA content in cell cycle wasdetected by flow cytometry. The cell apoptosis wasexamined by electron microscopy (EM) and TUNEL label.RESULTS: SHEE cells from the 6 th to 10 th passagesshowed cellular proliferation with a good differentiation.From the 12 th to the 16 th passages, many senescent andapoptotic cells appeared, and the telomere length sharplyshortened from 23 kb to 17 kb without expression of hTERTand telornerase activity. At the 20 th passage, SHEE cellsovercame the senescence and apoptosis and restored theirproliferative activity with expression of telomerase andhTERT at low levels, but the telomere length shortenedcontinuously to the lowest of 3 kb. After the 30 th passagecells proliferation was restored by increment of cells at S andG2M phase in the cell cycle end telomerase activity expressedat high levels and with maintenance of telomere length.CONCLUSION: At the early stage of SHEE cells, telomeresare shortened without expression of telomerase and hTERTcausing cellular senescence and cell death. From the 20 thto the 30 th passages, the activation of telomerase andmaintenance of telomere length show a progressive processfor immortalization of esophageal epithelial cells. Theexpression of telomerase may constitute a biomarker fordetection of

  5. Oxidative DNA damage correlates with cell immortalization and mir-92 expression in hepatocellular carcinoma

    OpenAIRE

    Romilda Cardin; Marika Piciocchi; Alessandro Sinigaglia; Enrico Lavezzo; Marina Bortolami; Andromachi Kotsafti; Umberto Cillo; Giacomo Zanus; Claudia Mescoli; Massimo Rugge; Fabio Farinati

    2012-01-01

    Abstract Background MicroRNAs expression has been extensively studied in hepatocellular carcinoma but little is known regarding the relationship, if any, with inflammation, production of reactive oxygen species (ROS), host’s repair mechanisms and cell immortalization. This study aimed at assessing the extent of oxidative DNA damage (8-hydroxydeoxyguanosine - 8-OHdG) in different phases of the carcinogenetic process, in relation to DNA repair gene polymorphism, telomeric dysfunction and to the...

  6. Genome-Wide Transcriptional Reorganization Associated with Senescence-to-Immortality Switch during Human Hepatocellular Carcinogenesis

    OpenAIRE

    Yildiz, Gokhan; Arslan-Ergul, Ayca; Bagislar, Sevgi; Konu, Ozlen; Yuzugullu, Haluk; Gursoy-Yuzugullu, Ozge; Ozturk, Nuri; Ozen, Cigdem; Ozdag, Hilal; Erdal, Esra; Karademir, Sedat; Sagol, Ozgul; Mizrak, Dilsa; BOZKAYA, Hakan; Ilk, Hakki Gokhan

    2013-01-01

    Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become “immortal”) by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated b...

  7. 求仙道旨在求功业--试论曹操游仙诗的思想实质%"Seeking the Fairyland of the Immortals",For the real purpose of making Immortal Contributions--The main ideas of Cao Cao's "Poetry about Immortals"

    Institute of Scientific and Technical Information of China (English)

    王丽珍

    2001-01-01

    曹操游仙诗并非悲叹人生无常、追慕神仙幻境、情绪消极颓废,其游仙诗的思想实质在于借游仙抒治世之抱负,求宏大之事业,建不朽之功绩。%Cao Cao's "Poetry about Immortals" did not really lament for the changing lives ofthe people, but actually it found the "fairyland of the immortals". His feelings showedlowspirits in his "poetry about immortals", but the main ideas were to express his great aspira-tions, administer the whole country well and make immortal contributions for history.

  8. Construction of an immortalized neural progenitor cell strain and analysis of its immunogenicity

    Institute of Scientific and Technical Information of China (English)

    Feng GAO; Yuke TIAN; Hui YANG; Ke AN; Ying XU; Xuebi TIAN; Chuanhan ZHANG

    2008-01-01

    Neural progenitor cells (NPC) are those that are the source of neural cells for cell transplantation and gene therapy. The shortage in quantity and the limited life spans of primary cultured cells limit its widespread use in basic research. Immortalized NPC, which also possess the capacity of self-renewal and can proliferate infinitely, can produce a large number of NPCs with stable phenotype and genotype. Here we report that an immortalized neural progenitor cell strain, which we named as INPC, was suc-cessfully established by gene-transfer of simian virus 40 large T antigen gene mediated by liposomes. The INPC retained the biological characteristics of its original cells and provided a safe and reliable cell platform for the treat-ment of central nervous system diseases and transgenic cell transplantation. INPC could express low levels of MHC antigens which was down-regulated after differentiation. This indicates that INPC possesses poor immunogenicity. The immortalized cells may show good long-term survival and do not elicit an acute immunological response follow-ing transplantation.

  9. Replication Timing of Human Telomeres is Conserved during Immortalization and Influenced by Respective Subtelomeres.

    Science.gov (United States)

    Piqueret-Stephan, Laure; Ricoul, Michelle; Hempel, William M; Sabatier, Laure

    2016-01-01

    Telomeres are specific structures that protect chromosome ends and act as a biological clock, preventing normal cells from replicating indefinitely. Mammalian telomeres are replicated throughout S-phase in a predetermined order. However, the mechanism of this regulation is still unknown. We wished to investigate this phenomenon under physiological conditions in a changing environment, such as the immortalization process to better understand the mechanism for its control. We thus examined the timing of human telomere replication in normal and SV40 immortalized cells, which are cytogenetically very similar to cancer cells. We found that the timing of telomere replication was globally conserved under different conditions during the immortalization process. The timing of telomere replication was conserved despite changes in telomere length due to endogenous telomerase reactivation, in duplicated homologous chromosomes, and in rearranged chromosomes. Importantly, translocated telomeres, possessing their initial subtelomere, retained the replication timing of their homolog, independently of the proportion of the translocated arm, even when the remaining flanking DNA is restricted to its subtelomere, the closest chromosome-specific sequences (inferior to 500 kb). Our observations support the notion that subtelomere regions strongly influence the replication timing of the associated telomere. PMID:27587191

  10. Hopelessly mortal: The role of mortality salience, immortality and trait self-esteem in personal hope.

    Science.gov (United States)

    Wisman, Arnaud; Heflick, Nathan A

    2016-08-01

    Do people lose hope when thinking about death? Based on Terror Management Theory, we predicted that thoughts of death (i.e., mortality salience) would reduce personal hope for people low, but not high, in self-esteem, and that this reduction in hope would be ameliorated by promises of immortality. In Studies 1 and 2, mortality salience reduced personal hope for people low in self-esteem, but not for people high in self-esteem. In Study 3, mortality salience reduced hope for people low in self-esteem when they read an argument that there is no afterlife, but not when they read "evidence" supporting life after death. In Study 4, this effect was replicated with an essay affirming scientific medical advances that promise immortality. Together, these findings uniquely demonstrate that thoughts of mortality interact with trait self-esteem to cause changes in personal hope, and that literal immortality beliefs can aid psychological adjustment when thinking about death. Implications for understanding personal hope, trait self-esteem, afterlife beliefs and terror management are discussed. PMID:25920481

  11. Hopelessly mortal: The role of mortality salience, immortality and trait self-esteem in personal hope.

    Science.gov (United States)

    Wisman, Arnaud; Heflick, Nathan A

    2016-08-01

    Do people lose hope when thinking about death? Based on Terror Management Theory, we predicted that thoughts of death (i.e., mortality salience) would reduce personal hope for people low, but not high, in self-esteem, and that this reduction in hope would be ameliorated by promises of immortality. In Studies 1 and 2, mortality salience reduced personal hope for people low in self-esteem, but not for people high in self-esteem. In Study 3, mortality salience reduced hope for people low in self-esteem when they read an argument that there is no afterlife, but not when they read "evidence" supporting life after death. In Study 4, this effect was replicated with an essay affirming scientific medical advances that promise immortality. Together, these findings uniquely demonstrate that thoughts of mortality interact with trait self-esteem to cause changes in personal hope, and that literal immortality beliefs can aid psychological adjustment when thinking about death. Implications for understanding personal hope, trait self-esteem, afterlife beliefs and terror management are discussed.

  12. Establishment and transformation of telomerase-immortalized human small airway epithelial cells by heavy ions

    Science.gov (United States)

    Zhao, Y. L.; Piao, C. Q.; Hei, T. K.

    Previous studies from this laboratory have identified a number of causally linked genes including the novel tumor suppressor Betaig-h3 that were differentially expressed in radiation induced tumorigenic BEP2D cells. To extend these studies using a genomically more stable bronchial cell line, we show here that ectopic expression of the catalytic subunit of telomerase (hTERT) in primary human small airway epithelial (SAE) cells resulted in the generation of several clonal cell lines that have been continuously in culture for more than 250 population doublings and are considered immortal. Comparably-treated control SAE cells infected with only the viral vector senesced after less than 10 population doublings. The immortalized clones demonstrated anchorage dependent growth and are non-tumorigenic in nude mice. These cells show no alteration in the p53 gene but a decrease in p16 expression. Exponentially growing SAEh cells were exposed to graded doses of 1 GeV/nucleon of 56Fe ions accelerated at the Brookhaven National Laboratory. Irradiated cells underwent gradual phenotypic alterations after extensive in vitro cultivation. Transformed cells developed through a series of successive steps before becoming anchorage independent in semisolid medium. These findings indicate that hTERT-immortalized cells, being diploid and chromosomal stable, should be a useful model in assessing mechanism of radiation carcinogenesis.

  13. Immune activation induces immortalization of HTLV-1 LTR-Tax transgenic CD4+ T cells.

    Science.gov (United States)

    Swaims, Alison Y; Khani, Francesca; Zhang, Yingyu; Roberts, Arthur I; Devadas, Satish; Shi, Yufang; Rabson, Arnold B

    2010-10-21

    Infection with the human T-cell leukemia virus-1 (HTLV-1) results in a variety of diseases including adult T-cell leukemia/lymphoma (ATL). Although the pathogenesis of these disorders is poorly understood, it involves complex interactions with the host immune system. Activation of infected T cells may play an important role in disease pathogenesis through induction of the oncogenic HTLV-1 Tax transactivator protein. To test this hypothesis, we employed transgenic mice in which Tax is regulated by the HTLV-1 LTR. T-cell receptor stimulation of LTR-Tax CD4(+) T cells induced Tax expression, hyper-proliferation, and immortalization in culture. The transition to cellular immortalization was accompanied by markedly increased expression of the antiapoptotic gene, mcl-1, previously implicated as important in T-cell survival. Immortalized cells exhibited a CD4(+)CD25(+)CD3(-) phenotype commonly observed in ATL. Engraftment of activated LTR-Tax CD4(+) T cells into NOD/Shi-scid/IL-2Rγ null mice resulted in a leukemia-like phenotype with expansion and tissue infiltration of Tax(+), CD4(+) lymphocytes. We suggest that immune activation of infected CD4(+) T cells plays an important role in the induction of Tax expression, T-cell proliferation, and pathogenesis of ATL in HTLV-1-infected individuals. PMID:20634377

  14. Spontaneous immortalization of cultured skin fibroblasts obtained from a high-dose atomic bomb survivor

    International Nuclear Information System (INIS)

    Two immortal fibroblastic cell strains (substrains) were established by culturing healthy skin cells obtained from a high-dose atomic bomb survivor (female, age 76 years, 5.14 Gy) for more than 4 years. Designated FM-U and FM-M, the two substrains share the same marker chromosome, t(5q-;6p+), but are karyotypically different, possessing hypodiploid chromosome numbers (39-43) in the former and hypertriploid (69-76) in the latter. Thus far, the two strains have passed through 117 and 156 subcultures or more than 230 and 310 cumulative population doublings, respectively, each passage requiring 4-6 days in the former and 3-4 days in the latter. In the process of immortalization, sequential rearrangement among various chromosomes presumably due to telomeric and interstitial telomeric fusions took place following the telomere shortening, particularly in the senescence and postsenescence phase cells. Of particular interest is the fact that loss of heterozygosity (LOH) of the p53 gene was demonstrated in these immortalized cell populations. In addition, the allelic patterns of the LOH of p53 differed. Further evidence indicative of infinite proliferation was demonstrated in both strains, such as the telomere elongation and the significantly low frequency of cells possessing dicentric chromosomes

  15. Lower liver cancer risk with antiviral therapy in chronic hepatitis B patients with normal to minimally elevated ALT and no cirrhosis

    Science.gov (United States)

    Hoang, Joseph K.; Yang, Hwai-I; Le, An; Nguyen, Nghia H.; Lin, Derek; Vu, Vinh D.; Chaung, Kevin; Nguyen, Vincent; Trinh, Huy N.; Li, Jiayi; Zhang, Jian Q.; Chen, Chien-Jen; Nguyen, Mindie H.

    2016-01-01

    Abstract For chronic hepatitis B (CHB), alanine aminotransferase (ALT) ≥2 × upper limit of normal (ULN) is often used as a major criteria to initiate treatment in absence of cirrhosis, though patients with lower ALT may not be free from future risk of hepatocellular carcinoma (HCC). We aimed to examine the effect of antiviral therapy on HCC incidence based on ALT levels. We performed a retrospective study on 3665 patients consisting of United States and Taiwanese REVEAL-HBV cohort who were consecutive, treatment-naïve, noncirrhotic CHB patients aged ≥40 years. Patients were categorized by ALT cutoffs (≥2 × ULN vs <2 × ULN) and subgrouped by treatment status. Kaplan–Meier and Cox proportional hazards models were used to calculate cumulative incidence and hazard ratio (HR) of HCC adjusting for REACH-B scores. A total of 202 patients developed HCC. Antiviral treatment significantly reduced HCC risk: HR 0.24, 95% confidence interval 0.10–0.58; P = 0.001. HCC incidence per 100,000 person-years was significantly higher in untreated versus treated patients, even for those with ALT < 2 × ULN: 314.46 versus 0 per 100,000 person-years, P = 0.0042. For patients with Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) ≥ 2000 IU/mL, the number-needed-to-treat (NNT) were 15 and 14 to prevent 1 incident HCC at year 10 for patients with ALT < 2 × ULN and ≥2 × ULN, respectively. After adjustment by REACH-B score, antiviral treatment significantly decreased HCC incidence even in patients with ALT < 2 × ULN. NNT to prevent 1 incident HCC after 10 years of therapy was low (14–15) in patients with mildly elevated HBV DNA ≥ 2000 IU/mL regardless of ALT levels. PMID:27495067

  16. Mre11 and Blm-Dependent Formation of ALT-Like Telomeres in Ku-Deficient Ustilago maydis.

    Directory of Open Access Journals (Sweden)

    Eun Young Yu

    2015-10-01

    Full Text Available A subset of human cancer cells uses a specialized, aberrant recombination pathway known as ALT to maintain telomeres, which in these cells are characterized by complex aberrations including length heterogeneity, high levels of unpaired C-strand, and accumulation of extra-chromosomal telomere repeats (ECTR. These phenotypes have not been recapitulated in any standard budding or fission yeast mutant. We found that eliminating Ku70 or Ku80 in the yeast-like fungus Ustilago maydis results initially in all the characteristic telomere aberrations of ALT cancer cells, including C-circles, a highly specific marker of ALT. Subsequently the ku mutants experience permanent G2 cell cycle arrest, accompanied by loss of telomere repeats from chromosome ends and even more drastic accumulation of very short ECTRs (vsECTRs. The deletion of atr1 or chk1 rescued the lethality of the ku mutant, and "trapped" the telomere aberrations in the early ALT-like stage. Telomere abnormalities are telomerase-independent, but dramatically suppressed by deletion of mre11 or blm, suggesting major roles for these factors in the induction of the ALT pathway. In contrast, removal of other DNA damage response and repair factors such as Rad51 has disparate effects on the ALT phenotypes, suggesting that these factors process ALT intermediates or products. Notably, the antagonism of Ku and Mre11 in the induction of ALT is reminiscent of their roles in DSB resection, in which Blm is also known to play a key role. We suggest that an aberrant resection reaction may constitute an early trigger for ALT telomeres, and that the outcomes of ALT are distinct from DSB because of the unique telomere nucleoprotein structure.

  17. Mre11 and Blm-Dependent Formation of ALT-Like Telomeres in Ku-Deficient Ustilago maydis.

    Science.gov (United States)

    Yu, Eun Young; Pérez-Martín, José; Holloman, William K; Lue, Neal F

    2015-10-01

    A subset of human cancer cells uses a specialized, aberrant recombination pathway known as ALT to maintain telomeres, which in these cells are characterized by complex aberrations including length heterogeneity, high levels of unpaired C-strand, and accumulation of extra-chromosomal telomere repeats (ECTR). These phenotypes have not been recapitulated in any standard budding or fission yeast mutant. We found that eliminating Ku70 or Ku80 in the yeast-like fungus Ustilago maydis results initially in all the characteristic telomere aberrations of ALT cancer cells, including C-circles, a highly specific marker of ALT. Subsequently the ku mutants experience permanent G2 cell cycle arrest, accompanied by loss of telomere repeats from chromosome ends and even more drastic accumulation of very short ECTRs (vsECTRs). The deletion of atr1 or chk1 rescued the lethality of the ku mutant, and "trapped" the telomere aberrations in the early ALT-like stage. Telomere abnormalities are telomerase-independent, but dramatically suppressed by deletion of mre11 or blm, suggesting major roles for these factors in the induction of the ALT pathway. In contrast, removal of other DNA damage response and repair factors such as Rad51 has disparate effects on the ALT phenotypes, suggesting that these factors process ALT intermediates or products. Notably, the antagonism of Ku and Mre11 in the induction of ALT is reminiscent of their roles in DSB resection, in which Blm is also known to play a key role. We suggest that an aberrant resection reaction may constitute an early trigger for ALT telomeres, and that the outcomes of ALT are distinct from DSB because of the unique telomere nucleoprotein structure.

  18. Hepatocellular carcinoma-derived exosomes promote motility of immortalized hepatocyte through transfer of oncogenic proteins and RNAs.

    Science.gov (United States)

    He, Mian; Qin, Hao; Poon, Terence C W; Sze, Siu-Ching; Ding, Xiaofan; Co, Ngai Na; Ngai, Sai-Ming; Chan, Ting-Fung; Wong, Nathalie

    2015-09-01

    Exosomes are increasingly recognized as important mediators of cell-cell communication in cancer progression through the horizontal transfer of RNAs and proteins to neighboring or distant cells. Hepatocellular carcinoma (HCC) is a highly malignant cancer, whose metastasis is largely influenced by the tumor microenvironment. The possible role of exosomes in the interactions between HCC tumor cell and its surrounding hepatic milieu are however largely unknown. In this study, we comprehensively characterized the exosomal RNA and proteome contents derived from three HCC cell lines (HKCI-C3, HKCI-8 and MHCC97L) and an immortalized hepatocyte line (MIHA) using Ion Torrent sequencing and mass spectrometry, respectively. RNA deep sequencing and proteomic analysis revealed exosomes derived from metastatic HCC cell lines carried a large number of protumorigenic RNAs and proteins, such as MET protooncogene, S100 family members and the caveolins. Of interest, we found that exosomes from motile HCC cell lines could significantly enhance the migratory and invasive abilities of non-motile MIHA cell. We further demonstrated that uptake of these shuttled molecules could trigger PI3K/AKT and MAPK signaling pathways in MIHA with increased secretion of active MMP-2 and MMP-9. Our study showed for the first time that HCC-derived exosomes could mobilize normal hepatocyte, which may have implication in facilitating the protrusive activity of HCC cells through liver parenchyma during the process of metastasis.

  19. Development of a Full-Thickness Human Gingiva Equivalent Constructed from Immortalized Keratinocytes and Fibroblasts.

    Science.gov (United States)

    Buskermolen, Jeroen K; Reijnders, Christianne M A; Spiekstra, Sander W; Steinberg, Thorsten; Kleverlaan, Cornelis J; Feilzer, Albert J; Bakker, Astrid D; Gibbs, Susan

    2016-08-01

    Organotypic models make it possible to investigate the unique properties of oral mucosa in vitro. For gingiva, the use of human primary keratinocytes (KC) and fibroblasts (Fib) is limited due to the availability and size of donor biopsies. The use of physiologically relevant immortalized cell lines would solve these problems. The aim of this study was to develop fully differentiated human gingiva equivalents (GE) constructed entirely from cell lines, to compare them with the primary cell counterpart (Prim), and to test relevance in an in vitro wound healing assay. Reconstructed gingiva epithelium on a gingiva fibroblast-populated collagen hydrogel was constructed from cell lines (keratinocytes: TERT or HPV immortalized; fibroblasts: TERT immortalized) and compared to GE-Prim and native gingiva. GE were characterized by immunohistochemical staining for proliferation (Ki67), epithelial differentiation (K10, K13), and basement membrane (collagen type IV and laminin 5). To test functionality of GE-TERT, full-thickness wounds were introduced. Reepithelialization, fibroblast repopulation of hydrogel, metabolic activity (MTT assay), and (pro-)inflammatory cytokine release (enzyme-linked immunosorbent assay) were assessed during wound closure over 7 days. Significant differences in basal KC cytokine secretion (IL-1α, IL-18, and CXCL8) were only observed between KC-Prim and KC-HPV. When Fib-Prim and Fib-TERT were stimulated with TNF-α, no differences were observed regarding cytokine secretion (IL-6, CXCL8, and CCL2). GE-TERT histology, keratin, and basement membrane protein expression very closely represented native gingiva and GE-Prim. In contrast, the epithelium of GE made with HPV-immortalized KC was disorganized, showing suprabasal proliferating cells, limited keratinocyte differentiation, and the absence of basement membrane proteins. When a wound was introduced into the more physiologically relevant GE-TERT model, an immediate inflammatory response (IL-6, CCL2, and

  20. Loss of ATRX Suppresses Resolution of Telomere Cohesion to Control Recombination in ALT Cancer Cells.

    Science.gov (United States)

    Ramamoorthy, Mahesh; Smith, Susan

    2015-09-14

    The chromatin-remodeler ATRX is frequently lost in cancer cells that use ALT (alternative lengthening of telomeres) for telomere maintenance, but its function in telomere recombination is unknown. Here we show that loss of ATRX suppresses the timely resolution of sister telomere cohesion that normally occurs prior to mitosis. In the absence of ATRX, the histone variant macroH2A1.1 binds to the poly(ADP-ribose) polymerase tankyrase 1, preventing it from localizing to telomeres and resolving cohesion. The resulting persistent telomere cohesion promotes recombination between sister telomeres, while it suppresses inappropriate recombination between non-sisters. Forced resolution of sister telomere cohesion induces excessive recombination between non-homologs, genomic instability, and impaired cell growth, indicating the ATRX-macroH2A1.1-tankyrase axis as a potential therapeutic target in ALT tumors. PMID:26373281

  1. Determination of mask induced polarization effects on AltPSM mask structures

    Science.gov (United States)

    Hollein, Ingo; Teuber, Silvio; Bubke, Karsten

    2005-06-01

    In the process of discussion of possible mask-types for the 5x nm node (half-pitch) and below, the alternating phase-shifting mask (AltPSM) is a potential candidate to be screened. The current scenario suggests using 193 nm immersion lithography with NA values of up to 1.2 and above. New optical effects from oblique incident angles, mask-induced polarization of the transmitted light and birefringence from the substrate need to be taken into account when the optical performance of a mask is evaluated. This paper addresses mask induced polarization effects from dense lines-and-space structures on a real mask. Measurements of the polarization dependent diffraction efficiencies have been performed on AltPSM masks. Experimental results show good agreement with simulations. A comparison with Binary Masks is made.

  2. Telomeric overhang length determines structural dynamics and accessibility to telomerase and ALT associated proteins

    OpenAIRE

    Hwang, Helen; Kreig, Alex; Calvert, Jacob; Lormand, Justin; Kwon, Yongho; Daley, James M.; Sung, Patrick; Opresko, Patricia L.; Myong, Sua

    2014-01-01

    The G-rich single stranded DNA at the 3′ end of human telomeres can self-fold into G-quaduplex (GQ). However, telomere lengthening by telomerase or the recombination-based alternative lengthening of telomere (ALT) mechanism requires protein loading on the overhang. Using single molecule fluorescence spectroscopy we discovered that lengthening the telomeric overhang also increased the rate of dynamic exchanges between structural conformations. Overhangs with five to seven TTAGGG repeats, compa...

  3. Der alte Patient in der Intensivmedizin - Was macht wann noch Sinn?

    Directory of Open Access Journals (Sweden)

    Valentin A

    2013-01-01

    Full Text Available Die zunehmende Alterung der Bevölkerung in hoch entwickelten Ländern hat einen profunden Einfluss auf die Intensivmedizin. So zeigen etwa Daten von Intensivpatienten aus einer großen österreichischen Datenbank einen Anteil von 20 % mit einem Alter ≥ 80 Jahre. Alter per se stellt kein Ausschlusskriterium für eine Intensivstationsaufnahme dar. Alte Patienten sind jedoch häufig durch multiple Ko-Morbiditäten belastet und weisen eine eingeschränkte physiologische Reserve auf. Nachdem alte Patienten ein sehr heterogenes Kollektiv darstellen und keine allgemein akzeptierten Kriterien für eine Aufnahme und Behandlung an der Intensivstation existieren, muss jede Entscheidung auf der Basis einer umfassenden Abwägung der individuellen Situation getroffen werden. Die Perspektive nach einem möglichen Überleben der kritischen Erkrankung stellt den wichtigsten Endpunkt dar und geht weit über die Frage des alleinigen Überlebens hinaus. Viele alte Patienten haben eine Chance, auch nach einer lebensbedrohlichen Erkrankung zu einer akzeptablen Lebensqualität zurückzukehren. Im Hinblick auf die Begrenztheit menschlichen Lebens ist es jedoch nicht gerechtfertigt, eine Intensivtherapie bei älteren Patienten zu beginnen oder fortzuführen, wenn nicht eine begründbare Aussicht auf einen Benefit besteht, welcher nicht nur durch das Überleben definiert ist.

  4. HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT.

    Directory of Open Access Journals (Sweden)

    Shuo Wang

    Full Text Available Gene polymorphisms associated so far with body mass index (BMI can explain only 1.18-1.45% of observed variation in BMI. Recent studies suggest that epigenetic modifications, especially DNA methylation, could contribute to explain part of the missing heritability, and two epigenetic genome-wide analysis studies (EWAS have reported that Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A methylation was associated with BMI or BMI change. We therefore assessed whether the HIF3A methylation is associated with obesity and other obesity-related phenotypes in Chinese children. The subjects included 110 severe obese cases aged 7-17y and 110 normal-weight controls matched by age and gender for measurement of blood DNA methylation levels at the HIF3A gene locus using the Sequenom's MassARRAY system. We observed significantly higher methylation levels in obese children than in controls at positions 46801642 and 46801699 in HIF3A gene (P<0.05, and found positive associations between methylation and alanine aminotransferase (ALT levels adjusted by gender, age and BMI at the position 46801699 (r = 0.226, P = 0.007. These results suggest that HIF3A DNA methylation is associated with childhood obesity, and has a BMI-independent association with ALT. The results provide evidence for identifying epigenetic factors of elivated ALT and may be useful for risk assessment and personalized medicine of liver diseases such as non-alcoholic fatty liver disease (NAFLD.

  5. Twist-3 fragmentation effects for ALT in light hadron production from proton–proton collisions

    Directory of Open Access Journals (Sweden)

    Y. Koike

    2016-01-01

    Full Text Available We compute the contribution from the twist-3 fragmentation function for light hadron production in collisions between transversely and longitudinally polarized protons, i.e., p↑p→→hX, which can cause a double-spin asymmetry (DSA ALT. This is a naïve T-even twist-3 observable that we analyze in collinear factorization using both Feynman gauge and lightcone gauge as well as give a general proof of color gauge invariance. So far only twist-3 effects in the transversely polarized proton have been studied for ALT in p↑p→→hX. However, there are indications that the naïve T-odd transverse single-spin asymmetry (SSA AN in p↑p→hX is dominated not by such distribution effects but rather by a fragmentation mechanism. Therefore, one may expect similarly that the fragmentation contribution is important for ALT. Given possible plans at RHIC to measure this observable, it is timely to provide a calculation of this term.

  6. TEOG kapsamında uygulanan matematik alt testi ile matematik mazeret alt testinin istatistiksel eşitliğinin sınanması

    OpenAIRE

    Özkan, Mustafa

    2015-01-01

          Bu çalışmada 2013-2014 eğitim-öğretim yılı I. yarıyılında MEB tarafından yapılan ve Temel Eğitimden Ortaöğretime Geçiş Sistemi (TEOG) kapsamında uygulanan Merkezi Ortak Sınavlar (MOS)’dan Matematik ve Matematik mazeret alt testlerinden elde edilen puanların Klasik Test Kuramı (KTK)’ne dayalı test eşitleme yöntemlerinden doğrusal ve eşit yüzdelikli eşitleme yöntemleri kullanılarak eşitlenmesi ve bu yöntemlerden en uygun olanının belirlenmesi a...

  7. Analysis of blood screening results before and after changing critical value of ALT%血液筛查 ALT 临界值的变更后检验结果分析

    Institute of Scientific and Technical Information of China (English)

    冯秋霞; 杨忠思; 潘海平; 刘丽; 许雷

    2015-01-01

    Objective To analyze the blood screening results after adjustment of critical value 40 to 50 U/L and to observe the effect of reducing blood scrap rate and to discuss the correlation between ALT and HBV,HCV infection.Methods We screened 2656 blood donors (ALT >40 U/L)by serological and nucleic acid amplification testing(NAT)in Qingdao blood center from 2013 to 2014,and conducted the correlation analysis by chi square test.Results 1 771 cases (66.68%)were ALT 40-50 U/L,including 6 cases of HBsAg ELISA (+),2 cases NAT (+),4 cases NAT(-).In the 8 cases of anti-HCV ELISA (+)samples,4 cases NAT (+),3 cases NAT (-),1 case with positive TP without NAT result.In 885 blood donors with ALT>50 U/L,5 cases were HBsAg-reactive,7 cases were anti-HCV-reactive,and 873 cases were negative.Related statistics showed that there was no signifi-cant difference between ALT and HBV infection (P 0.05).Conclusion The proportion of blood donors with ALT 40-50 U/L is much higher than that with ALT >50 U/L do-nors.Adjustment of the critical value greatly reduces blood scrap rate.Elevated ALT is associated with the infection of HBV but not with HCV.%目的:通过分析对比丙氨酸氨基转移酶(ALT)临界值调整后40~50 U/L 和大于50 U/L 献血者的血液检测结果,观察降低血液报废率效果和探讨 ALT 异常与 HBV 和 HCV 感染的相关性。方法分析青岛市中心血站2013~2014年2656例ALT>40 U/L 的无偿献血者的 HBV 和 HCV 血清学和核酸检测(NAT)结果并进行相关性研究。结果ALT 在40~50 U/L 者共1771例(66.68%),其中6例 HBsAg ELISA(+),NAT(+)2例,NAT(-)4例,8例抗-HCV 抗体 ELISA(+)样本中,NAT (+)4例,NAT(-)3例,1例 TP 阳性未做 NAT。ALT>50 U/L 的885例献血者中,HBsAg 反应性者5例,抗-HCV 抗体反应性者7例,全无反应性者873例。相关性统计数据表明:ALT 与 HBV 差异无统计学意义(P 0.05)。结论ALT 在40~50 U/L 的献血者的比例远远高于50 U/L 以上的献血者,调整临界值后大大降低了血液报废率,ALT

  8. Retrovirus-Mediated Gene Transfer in Immortalization of Progenitor Hair Cell Lines in Newborn Rat

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yuan; ZHAI Suo-qiang; SONG Wei; GUO Wei; ZHENG Gui-liang; HU Yin-yan

    2008-01-01

    Objective To present an experimental method that allows isolation of greater epithelial ridge (GER) and lesser epithelial ridge(LER) cells from postnatal rat cochleae using a combinatorial approach of enzymatic digestion and mechanical separation and to investigate a retrovirus-mediated gene transfer technique for its possibl utility in immortalization of the GER and LER cell lines, in an effort to establish an in vitro model system of hair cell differentiation. Methods GER and LER cells were dissected from postnatal rat cochleae and immortalized by transferring the SV40 large T antigen using a retrovirus. The established cell lines were confirmed through morphology observation, immunnocytochemical staining and RT-PCR analysis. The Hathl gene was transferred into the cell lines using adenovirus-mediated techniques to explore their potential to differentiate into hair cells. Results The established cell lines were stably maintained for more than 20 passages and displayed many features similar to primary GER and LER cells. They grew in patches and assumed a polygonal morphology. Immunostaining showed labeling by SV40 large T antigen and Islet1 (a specific marker for GER and LER). All passages of the cell lines expressed SV40 large T antigen on RT-PCR analysis. The cells also showed the capability to differenti-ate into hair cell-like cells when forced to express Hathl. Conclusion Retrovirus-mediated gene transfer can be used in establishing immortalized progenitor hair cell lines in newborn rat, which may provide an invaluable system for studying hair cell differentiation and regeneration for new treatment of sensory hearing loss caused by hair cell loss.

  9. Benzo (a) pyrene induced tumorigenesity of human immortalized oral epithelial cells: transcription profiling

    Institute of Scientific and Technical Information of China (English)

    LI Jin-zhong; PAN Hong-ya; ZHENG Jia-wei; ZHOU Xiao-jian; ZHANG Ping; CHEN Wan-tao; ZHANG Zhi-yuan

    2008-01-01

    Background The present study was designed to examine and analyze the global gene expression changes during the tumorigenesis of a human immortalized oral epithelial cell line, and search for the possible genes that may play a role in the carcinogenesis of oral cancer associated with benzo (a) pyrene.Methods The human immortalized oral epithelial cells, which have been established through transfection of E6/E7 genasof human papillomavirus type 16 and proved to be non-tumorigenic in nude mice, were treated with benzo (a) pyrene.Tumorigenesity of the treated cells were examined through nude mice subcutaneous injection. The global gene expression profiles of immortalized cells and the tumorigenic cells were acquired through hybridization of a microarray of Affymetrix U133 plus 2.0. The data were analyzed using Spring 7.0 software and treated statistically using one-way analysis of variance (ANOVA). The differentially expressed genes were classified using a Venn diagram and annotated with gene ontology. Several highlighted genes were validated in cells using a real-time polymerase chain reaction.Results There were 883 differentially expressed genes during the tumorigenesis and most of them changed expression in the early stage of tumorigenesis. These genes mainly involved in macromolecule metabolism and signal transduction,possessed the molecular function of transition metal ion binding, nucleotide binding and kinase activity; their protein products were mainly integral to membranes or localized in the nucleus and cytoskeleton. The expression patterns of IGFBP3, S100A8, MAP2K, KRT6B, GDF15, MET were validated in cells using a real-time polymerase chain reaction; the expression of IGFBP3 was further validated in clinical oral cancer specimens.Concluslona This study provides the global transcription profiling associated with the tumorigenesis of oral epithelial cells exposed to benzo (a) pyrene; IGFBP3 may play a potential role in the initiation of oral cancer related to

  10. Functional analysis of a highly conserved abundant larval transcript-2 (alt-2) intron 2 repeat region of lymphatic filarial parasites.

    Science.gov (United States)

    Sakthidevi, Moorthy; Hoti, Sugeerappa Laxmanappa; Kaliraj, Perumal

    2014-06-01

    The filarial-specific protein abundant larval transcript-2 (ALT-2) is expressed exclusively in the infective larval stage (L3) and is a crucial protein for establishing immunopathogenesis in human hosts. The alt-2 gene has a conserved minisatellite repeat (29 or 27bp) in intron 2 (IR2) whose significance within lymphatic filarial species is unknown. Here, we report the role of IR2 in the regulation of alt-2 gene expression using an in vitro model. Using electrophoretic mobility shift assays, we identified the presence of a putative nuclear protein binding region within IR2. Subsequent transient expression experiments in eukaryotic cell lines demonstrated that the IR2 downregulated the expression of a downstream luciferase reporter gene, which was further validated with RT-PCR. We therefore identify IR2 as a suppressor element that regulates L3 stage-specific expression of alt-2. PMID:24681262

  11. Road and Street Centerlines, Quich Alt rd, Published in 2005, 1:24000 (1in=2000ft) scale, Iron County.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — , published at 1:24000 (1in=2000ft) scale, was produced all or in part from Other information as of 2005. It is described as 'Quich Alt rd'. The extent of these...

  12. Survey of A_LT' asymmetries in semi-exclusive electron scattering on He4 and C12

    CERN Document Server

    Protopopescu, D; Holtrop, M; Adams, G; Ambrozewicz, P; Anciant, E; Anghinolfi, M; Asavapibhop, B; Asryan, G; Audit, G; Auger, T; Avakian, H; Bagdasaryan, H; Ball, J P; Barrow, S; Battaglieri, M; Beard, K; Bektasoglu, M; Bellis, M; Benmouna, N; Berman, B L; Bertozzi, W; Bianchi, N; Biselli, A S; Boiarinov, S; Bonner, B E; Bouchigny, S; Bradford, R; Branford, D; Briscoe, W J; Brooks, W K; Burkert, V D; Butuceanu, C; Calarco, J R; Carman, D S; Carnahan, B; Cetina, C; Chen, S; Cole, P L; Coleman, A; Cords, D; Corvisiero, P; Crabb, D; Crannell, H; Cummings, J P; De Sanctis, E; De Vita, R; Degtyarenko, P V; Dennis, L; Dharmawardane, K V; Dhuga, K S; Djalali, C; Dodge, G E; Doughty, D C; Dragovitsch, P; Dugger, M; Dytman, S; Dzyubak, O P; Egiyan, H; Egiyan, K S; Elouadrhiri, L; Empl, A; Eugenio, P; Fatemi, R; Feuerbach, R J; Forest, T A; Funsten, H; Gavalian, G; Gilad, S; Gilfoyle, G P; Giovanetti, K L; Girard, P; Gordon, C I O; Gothe, R W; Griffioen, K A; Guidal, M; Guillo, M R; Guler, N; Guo, L; Gyurjyan, V; Hadjidakis, C; Hakobyan, R S; Hardie, J; Heddle, D; Hicks, K; Hleiqawi, I; Hu, J; Hyde-Wright, C E; Ingram, W; Ireland, D; Ito, M M; Jenkins, D; Joo, K; Jüngst, H G; Kelley, J H; Kellie, J D; Khandaker, M; Kim, K Y; Kim, K; Kim, W; Klein, A; Klein, F J; Klimenko, A V; Klusman, M; Kossov, M; Kramer, L H; Kuhn, S E; Kühn, J; Lachniet, J; Laget, J M; Langheinrich, J; Lawrence, D; Lee, T; Ji Li; Livingston, K; Lukashin, K; Manak, J J; Marchand, C; McAleer, S; McLauchlan, S T; McNabb, J W C; Mecking, B A; Melone, J J; Mestayer, M D; Meyer, C A; Mikhailov, K; Minehart, R C; Mirazita, M; Miskimen, R; Morand, L; Morrow, S A; Muccifora, V; Müller, J; Mutchler, G S; Napolitano, J; Nasseripour, R; Nelson, S O; Niccolai, S; Niculescu, G; Niculescu, I; Niczyporuk, B B; Niyazov, R A; Nozar, M; O'Rielly, G V; Osipenko, M; Ostrovidov, A I; Park, K; Pasyuk, E A; Peterson, G; Philips, S A; Pivnyuk, N; Pocanic, D; Pogorelko, O I; Polli, E; Pozdniakov, S; Preedom, B M; Price, J W; Prok, Y; Qin, L M; Raue, B A; Riccardi, G; Ricco, G; Ripani, M; Ritchie, B G; Ronchetti, F; Rosner, G; Rossi, P; Rowntree, D; Rubin, P D; Sabati, F; Sabourov, K; Salgado, C; Santoro, J P; Sapunenko, V; Schumacher, R A; Serov, V S; Sharabyan, Yu G; Shaw, J; Simionatto, S; Skabelin, A V; Smith, E S; Smith, L C; Sober, D I; Spraker, M; Stavinsky, A V; Stepanyan, S; Stokes, B E; Stoler, P; Strauch, S; Taiuti, M; Taylor, S; Tedeschi, D J; Thoma, U; Thompson, R; Tkabladze, A; Todor, L; Tur, C; Ungaro, M; Vineyard, M F; Vlassov, A V; Wang, K; Weinstein, L B; Weller, H; Weygand, D P; Whisnant, C S; Williams, M; Wolin, E; Wood, M H; Yegneswaran, A; Yun, J; Zana, L; Zhang, B; Debruyne, D; Ryckebusch, J

    2004-01-01

    Single spin azimuthal asymmetries A_LT' were measured at Jefferson Lab using 2.2 and 4.4 GeV longitudinally polarized electrons incident on He4 and C12 targets in the CLAS detector. A_LT' is related to the imaginary part of the longitudinal-transverse interference and in quasifree nucleon knockout it provides an unambiguous signature for final state interactions (FSI). Experimental values of A_LT' were found to be below 5%, typically |A_LT'| < 3% for data with good statistical precision. Optical Model in Eikonal Approximation (OMEA) and Relativistic Multiple-Scattering Glauber Approximation (RMSGA) calculations are shown to be consistent with the measured asymmetries.

  13. H/sub. cap alpha. / monitors for the Advanced Limiter Test-II (ALT-II) on TEXTOR

    Energy Technology Data Exchange (ETDEWEB)

    Uckan, T.

    1988-05-01

    The H/sub ..cap alpha../ monitor system installed on TEXTOR in conjunction with the Advanced Limiter Test-II (ALT-II) toroidal belt pump limiter is introduced. The monitors are used to study edge particle fluxes and recycling, correlations to confinement properties of core and edge plasma with ALT-II, and also high-power auxiliary heating (/approximately/5 MW) during long-pulse (/approximately/4-s) operation of TEXTOR. A model of the edge particle flux based on the H/sub ..cap alpha../ measurements is presented. The ALT-II experiments are to be carried out in various phases. Here we discuss the results obtained from the monitor system during the initial phase of operations following the installation of the ALT-II limiter, with ohmic heating only. 15 refs., 21 figs.

  14. Hopelessly Mortal: The Role of Mortality Salience, Immortality and Trait Self-esteem in Personal Hope

    OpenAIRE

    Wisman, Arnaud; Heflick, Nathan A

    2015-01-01

    Do people lose hope when thinking about death? Based on Terror Management Theory, we predicted that thoughts of death (i.e., mortality salience) would reduce personal hope for people low, but not high, in self-esteem, and that this reduction in hope would be ameliorated by promises of immortality. In Studies 1 and 2, mortality salience reduced personal hope for people low in self-esteem, but not for people high in self-esteem. In Study 3, mortality salience reduced hope for people low in self...

  15. Determination of Drug Toxicity Using 3D Spheroids Constructed From an Immortal Human Hepatocyte Cell Line

    DEFF Research Database (Denmark)

    Fey, S. J.; Wrzesinski, Krzysztof

    2012-01-01

    Numerous publications have documented that the immortal cells grown in three-dimensional (3D) cultures possess physiological behavior, which is more reminiscent of their parental organ than when the same cells are cultivated using classical two-dimensional (2D) culture techniques. The goal...... that a precise dose can be provided in a manner similar to in vivo studies. This avoided correction of the actual dose given based on a protein determination after treatment (when some cells may have lysed). Conversion of published in vitro LC50 data (mM) for six common drugs (acetaminophen, amiodarone...

  16. A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B.

    Directory of Open Access Journals (Sweden)

    Wai-Kay Seto

    Full Text Available OBJECTIVE: We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg-positive and HBeAg-negative patients. METHODS: From 1994 to 2008, liver biopsy was performed on 319 treatment-naïve CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis. RESULTS: 211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5% HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading ≥ 7 or fibrosis score ≥ 3. There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women and patients with a normal ALT but exceeding the Prati criteria (p = 0.024. Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively. HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively. An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345 and -negative (p = 0.544 disease. There was no significant difference in fibrosis staging among ALT 1-2 × upper limit of normal (ULN and > × 2 ULN for both HBeAg-positive (p = 0.098 and -negative (p = 0.838 disease. CONCLUSION: An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.

  17. Incremental Predictive Value of Serum AST-to-ALT Ratio for Incident Metabolic Syndrome: The ARIRANG Study

    Science.gov (United States)

    Ahn, Song Vogue; Baik, Soon Koo; Cho, Youn zoo; Koh, Sang Baek; Huh, Ji Hye; Chang, Yoosoo; Sung, Ki-Chul; Kim, Jang Young

    2016-01-01

    Aims The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is of great interest as a possible novel marker of metabolic syndrome. However, longitudinal studies emphasizing the incremental predictive value of the AST-to-ALT ratio in diagnosing individuals at higher risk of developing metabolic syndrome are very scarce. Therefore, our study aimed to evaluate the AST-to-ALT ratio as an incremental predictor of new onset metabolic syndrome in a population-based cohort study. Material and Methods The population-based cohort study included 2276 adults (903 men and 1373 women) aged 40–70 years, who participated from 2005–2008 (baseline) without metabolic syndrome and were followed up from 2008–2011. Metabolic syndrome was defined according to the harmonized definition of metabolic syndrome. Serum concentrations of AST and ALT were determined by enzymatic methods. Results During an average follow-up period of 2.6-years, 395 individuals (17.4%) developed metabolic syndrome. In a multivariable adjusted model, the odds ratio (95% confidence interval) for new onset of metabolic syndrome, comparing the fourth quartile to the first quartile of the AST-to-ALT ratio, was 0.598 (0.422–0.853). The AST-to-ALT ratio also improved the area under the receiver operating characteristic curve (AUC) for predicting new cases of metabolic syndrome (0.715 vs. 0.732, P = 0.004). The net reclassification improvement of prediction models including the AST-to-ALT ratio was 0.23 (95% CI: 0.124–0.337, P<0.001), and the integrated discrimination improvement was 0.0094 (95% CI: 0.0046–0.0143, P<0.001). Conclusions The AST-to-ALT ratio independently predicted the future development of metabolic syndrome and had incremental predictive value for incident metabolic syndrome. PMID:27560931

  18. Correlation between Aminotransferase Ratio (AST/ALT and Other Biochemical Parameters in Chronic Liver Disease of Viral Origin

    Directory of Open Access Journals (Sweden)

    Shah Md Fazlul Karim

    2015-03-01

    Full Text Available Background: In recent years the ratio of aspartate aminotransferase (AST to alanine aminotransferase (ALT in patients of chronic liver disease (CLD of various origins has gained much attention. This variable is readily available, easy to interpret, and inexpensive and the clinical utility of the AST/ALT ratio in the diagnostic workup of patients with CLD is quite promising. Objective: The present study was designed to find out the link between aminotransferase (AST/ALT ratio with commonly measured biochemical parameters of liver function tests in CLD of viral origin. Materials and method: This cross sectional study was carried out in the department of Biochemistry, Sir Salimullah Medical College, Dhaka, Bangladesh. Forty four biopsy proven diagnosed subjects of chronic viral hepatitis without cirrhosis of both sex were selected purposively. With aseptic precaution 5 mL venous blood was collected from each subject and common liver function tests (serum AST, ALT, AST/ALT ratio, alkaline phosphatase, total bilirubin, serum total protein, serum albumin, serum globulin, serum albumin/globulin ratio, prothrombin time and viral serology (HBsAg, Anti HDV antibody, Anti HCV antibody were performed. Data were analyzed by SPSS version 19 for Windows. Pearson’s correlation test was done to determine association between AST/ALT with other biochemical parameters. Results: Mean(±SD age of the study subjects was 32.55±10.55 years (range 20-50 years with 48 (77.7% male and 14 (22.6% female subjects. Pearson’s correlation test was done between AST to ALT ratio with other biochemical parameters and prothrombin time showed significant positive correlation (p <0.01. Conclusion: In our study we found significant positive correlation between AST/ALT with prothrombin time in CLD subjects without cirrhosis.

  19. Assessment of french design method for flexible pavement by mean of the LCPC's ALT facility

    OpenAIRE

    Balay, Jean Maurice; Kerzreho, Jean Pierre

    2008-01-01

    One of the three rings of the LCPC's ALT facility has been equipped in 2002 with a 3 meters high waterproof concrete pit and a pumping station, making possible to completely control the water table level in the soil supporting the experimental pavement. The pit has been filled by clayey-silty sand, which the modulus varies from 110 to 85 MPa according to the water content. This soil has been chosen for its water-content susceptibility, but also for its permeability properties, making possible...

  20. The Photophysical Properties and Morphology of Fluorene- alt-benzene Based Conjugated Polymers

    Institute of Scientific and Technical Information of China (English)

    Guizhong Yang; Tianxi Liu; Min Wang; Peiyi Wu; Wei Huang

    2005-01-01

    @@ 1Introduction There has been wide interest in the photophysical properties of rod-like fluorene based conjugated polymers because of their potential applications in various optoelectronic devices, especially in polymers light-emitting diodes (PLEDs)[1]. In this work, a series of fluorene-alt-benzene based conjugated main chain polymers with different length alkyl side chains on phenylene ring were designed and successfully synthesized. The effect of alkyl chain length on the photophysical property, phase transition behavior and morphology structure of the polymers were investigated.

  1. Application of the Alt-Grassberger-Sandhas equations to the three-alpha model

    International Nuclear Information System (INIS)

    The three-alpha model of the 12C nucleus is calculated by solving the Alt-Grassberger-Sandhas (AGS) equations with effective cluster-cluster potentials directly derived from the resonating-group method and modified by the orthogonality-condition model or the fish-bone optical mode1 techniques. Instead of using Kukulin's pseudo-potential projection method for the Pauli-forbidden state which is approximative but the only method used up to now, we introduce a new exact method to give the transition matrices. The dependence of the 12C binding energy on the strength of Serber force is shown. (author)

  2. Age and the means of bypassing stasis are determinants of the intrinsic subtypes of immortalized human mammary epithelial cells

    Directory of Open Access Journals (Sweden)

    Jonathan K Lee

    2015-03-01

    Full Text Available Based on molecular features, breast cancers are grouped into intrinsic subtypes that have different prognoses and therapeutic response profiles. With increasing age, breast cancer incidence increases, with hormone receptor-positive and other luminal-like subtype tumors comprising a majority of cases. It is not known at what stage of tumor progression subtype specification occurs, nor how the process of aging affects the intrinsic subtype. We examined subtype markers in immortalized human mammary epithelial cell lines established following exposure of primary cultured cell strains to a two-step immortalization protocol that targets the two main barriers to immortality: stasis (stress-associated senescence and replicative senescence. Cell lines derived from epithelial cells obtained from non-tumorous pre- and post-menopausal breast surgery tissues were compared. Additionally, comparisons were made between lines generated using two different genetic interventions to bypass stasis: transduction of either an shRNA that down-regulated p16INK4A, or overexpressed constitutive active cyclin D1/CDK2. In all cases, the replicative senescence barrier was bypassed by transduction of c-Myc. Cells from all resulting immortal lines exhibited normal karyotypes. Immunofluorescence, flow cytometry, and gene expression analyses of lineage-specific markers were used to categorize the intrinsic subtypes of the immortalized lines. Bypassing stasis with p16 shRNA in young strains generated cell lines that were invariably basal-like, but the lines examined from older strains exhibited some luminal features such as keratin 19 and estrogen receptor expression. Overexpression of cyclin D1/CDK2 resulted in keratin 19 positive, luminal-like cell lines from both young and old strains, and the lines examined from older strains exhibited estrogen receptor expression. Thus age and the method of bypassing stasis are independent determinants of subtype in immortalized human

  3. Age and the means of bypassing stasis influence the intrinsic subtype of immortalized human mammary epithelial cells.

    Science.gov (United States)

    Lee, Jonathan K; Garbe, James C; Vrba, Lukas; Miyano, Masaru; Futscher, Bernard W; Stampfer, Martha R; LaBarge, Mark A

    2015-01-01

    Based on molecular features, breast cancers are grouped into intrinsic subtypes that have different prognoses and therapeutic response profiles. With increasing age, breast cancer incidence increases, with hormone receptor-positive and other luminal-like subtype tumors comprising a majority of cases. It is not known at what stage of tumor progression subtype specification occurs, nor how the process of aging affects the intrinsic subtype. We examined subtype markers in immortalized human mammary epithelial cell lines established following exposure of primary cultured cell strains to a two-step immortalization protocol that targets the two main barriers to immortality: stasis (stress-associated senescence) and replicative senescence. Cell lines derived from epithelial cells obtained from non-tumorous pre- and post-menopausal breast surgery tissues were compared. Additionally, comparisons were made between lines generated using two different genetic interventions to bypass stasis: transduction of either an shRNA that down-regulated p16(INK4A), or overexpressed constitutive active cyclin D1/CDK2. In all cases, the replicative senescence barrier was bypassed by transduction of c-Myc. Cells from all resulting immortal lines exhibited normal karyotypes. Immunofluorescence, flow cytometry, and gene expression analyses of lineage-specific markers were used to categorize the intrinsic subtypes of the immortalized lines. Bypassing stasis with p16 shRNA in young strains generated cell lines that were invariably basal-like, but the lines examined from older strains exhibited some luminal features such as keratin 19 and estrogen receptor expression. Overexpression of cyclin D1/CDK2 resulted in keratin 19 positive, luminal-like cell lines from both young and old strains, and the lines examined from older strains exhibited estrogen receptor expression. Thus age and the method of bypassing stasis independently influence the subtype of immortalized human mammary epithelial cells

  4. Immortalized Mouse Floxed Fam20c Dental Papillar Mesenchymal and Osteoblast Cell Lines Retain Their Primary Characteristics

    Science.gov (United States)

    Liu, Chao; Wang, Xiaofang; Zhang, Hua; Xie, Xiaohua; Liu, Peihong; Liu, Ying; Jani, Priyam H.; Lu, Yongbo; Chen, Shuo; Qin, Chunlin

    2016-01-01

    Fam20c is essential for the normal mineralization of dentin and bone. The generation of odontoblast and osteoblast cell lines carrying floxed Fam20c allele can offer valuable tools for the study of the roles of Fam20c in the mineralization of dentin and bone. The limited capability of the primary odontoblasts and osteoblasts to proliferate necessitates the development of odontoblast and osteoblast cell lines serving as substitutes for the study of differentiation and mineralization of the odontoblasts and osteoblasts. In this study, we established and characterized immortalized mouse floxed Fam20c dental papilla mesenchymal and osteoblast cell lines. The isolated primary mouse floxed Fam20c dental papilla mesenchymal cells and osteoblasts were immortalized by the infection of lentivirus containing Simian Virus 40 T-antigen (SV40 T-Ag). The immortalization of floxed Fam20c dental papilla mesenchymal cells and osteoblasts was verified by the long-term passages and genomic integration of SV40 T-Ag. The immortalized floxed Fam20c dental papilla mesenchymal and osteoblast cell lines not only proliferated at a high rate and retained the morphology of their primary counterparts, but also preserved the dentin and bone specific gene expression as the primary dental papilla mesenchymal cells and osteoblasts did. Consistently, the capability of the primary floxed Fam20c dental papilla mesenchymal cells and osteoblasts to mineralize was also inherited by the immortalized dental papilla mesenchymal and osteoblast cell lines. Thus, we have successfully generated the immortalized mouse floxed Fam20c dental papilla mesenchymal and osteoblast cell lines. PMID:25833681

  5. Attempting immortality

    Energy Technology Data Exchange (ETDEWEB)

    Krull, W. [GKSS-Forschungszentrum Geesthacht GmbH (Germany)

    1995-12-01

    The world`s population of research reactors is growing old. Many have been adapted to serve new purposes over their lives, from testing materials for nuclear power programmes and supporting neutron physics experiments, to colouring gemstones, doping silicon and generating medical isotopes. In the first article of this survey of research reactor issues, Wilfried Krull from GKSS in Germany describes the effects on a reactor of supporting these changes in application as ``design ageing`` . Managing this and other symptoms of ageing to extend plant life is a key task for operators, and Krull discusses the efforts being made internationally to handle them. Eventually, terminal decline of one vital component can determine when a reactor has to be shutdown for refurbishment. For BR2 in Belgium, it was the beryllium matrix. Edgar Koonen from SCK-CEN explains work being done to replace it and extend reactor life for around 15 years. The Triga at the University of Austria`s Atomic Institute has already been running for over 30 years and Helmuth Bock, of the Institute, credits its good health to thorough routine maintenance procedures and custom-made tools for the work. The HANARO reactor in Korea achieved first criticality in February this year - one of the few new research reactors to have started up in recent years. Seong-yun Kim of KAERI describes its design and uses, including medical isotope production. About 80% of medical Mo-99 comes from the 38-year-old NRU in Canada. Russell Ball from B and W Nuclear Environmental Services describes a conceptual reactor for dedicated Mo-99 production in the last article of the survey. (UK).

  6. Immortal Melody

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    China celebrates 50 years of the Butterfly Lovers violin concerto The legend of Liang Shanbo and Zhu Yingtai, known as China’s Romeo and Juliet, has moved generations of Chinese. The doleful and romantic story of

  7. Immortalization of Human Precartilaginous Stem Cells by Transfecting SV40Tag

    Institute of Scientific and Technical Information of China (English)

    Junfang WANG; Huang FANG; Renyun XIA; Anming CHEN; Hao CHENG

    2009-01-01

    Immortalized human precartilaginous stem cells (IPSCs) were established to provide stable cell resource for the study of the molecular mechanism of gene targeting on the differentiation of PSCs.Plasmid pCMVSV40T/PUR containing simian virus 40 large T antigen gene (SV40Tag) was transfected into human PSCs by using lipofectin transfection.Colonies were isolated by puromycin selection and expanded by multiple passages,lmmunohistochemistry,RT-PCR and Southern blotting were used to identify the transfected cells and to detect the expression and integration of SV40Tag in expanded cell lines.The positive colonies were isolated and subcultured,designated immortalized precartilaginous stem cells (IPSCs),which were confirmed as fibroblast growth factor receptor-3 (FGFR-3) positive cells by immunohistochemistry and RT-PCR.SV40Tag cDNA was found in cultured IPSCs of passage 8 by Southern blotting,and the expressions of SV40Tag mRNA and protein were confirmed by RT-PCR.These findings suggested that IPSCs strain with SV40Tag was constructed successfully.

  8. "Almha La Vengadora": Protagonista del indigenismo de neovanguardia alteño

    Directory of Open Access Journals (Sweden)

    Maria Irina Soto-Mejia

    2016-03-01

    Este artículo discute la obra de Crispín Portugal (1976-2007, un escritor alteño, en el contexto de la lucha contra la pobreza y el racismo que enfrentan a las ciudades de El Alto y La Paz, y del movimiento en contra del mercado  que comenzó en Argentina produciendo libros con tapas de cartón compradas a los cartoneros. Portugal y otros escritores indígenas iniciaron un proyecto editorial llamado Yerba Mala Cartonera, que cuenta con su propio blog, para diseminar la literatura boliviana que no cuenta con otros medios de difusión. A través de la revisión de un cuento de Portugal (Almha La Vengadora que describe a una chola luchadora de El Alto cuyo nombre en el cuadrilátero es “la vengadora”, este trabajo plantea la configuración de un indigenismo alteño de neovanguardia equiparable al vanguardismo de Gamaliel Churata.  Con este propósito, presta especial atención a El Alto –la ciudad indígena más grande de Latinoamérica- situándolo como escenario clave para el desarrollo de una neovanguardia que se alimenta del neoliberalismo fallido para configurar una propuesta de modernidad que recupera el pasado indígena aymara para inventar otras formas de futuro.

  9. Balancing Benefits and Risks of Immortal Data: Participants' Views of Open Consent in the Personal Genome Project.

    Science.gov (United States)

    Zarate, Oscar A; Brody, Julia Green; Brown, Phil; Ramirez-Andreotta, Mónica D; Perovich, Laura; Matz, Jacob

    2016-01-01

    An individual's health, genetic, or environmental-exposure data, placed in an online repository, creates a valuable shared resource that can accelerate biomedical research and even open opportunities for crowd-sourcing discoveries by members of the public. But these data become "immortalized" in ways that may create lasting risk as well as benefit. Once shared on the Internet, the data are difficult or impossible to redact, and identities may be revealed by a process called data linkage, in which online data sets are matched to each other. Reidentification (re-ID), the process of associating an individual's name with data that were considered deidentified, poses risks such as insurance or employment discrimination, social stigma, and breach of the promises often made in informed-consent documents. At the same time, re-ID poses risks to researchers and indeed to the future of science, should re-ID end up undermining the trust and participation of potential research participants. The ethical challenges of online data sharing are heightened as so-called big data becomes an increasingly important research tool and driver of new research structures. Big data is shifting research to include large numbers of researchers and institutions as well as large numbers of participants providing diverse types of data, so the participants' consent relationship is no longer with a person or even a research institution. In addition, consent is further transformed because big data analysis often begins with descriptive inquiry and generation of a hypothesis, and the research questions cannot be clearly defined at the outset and may be unforeseeable over the long term. In this article, we consider how expanded data sharing poses new challenges, illustrated by genomics and the transition to new models of consent. We draw on the experiences of participants in an open data platform-the Personal Genome Project-to allow study participants to contribute their voices to inform ethical consent

  10. Balancing Benefits and Risks of Immortal Data: Participants' Views of Open Consent in the Personal Genome Project.

    Science.gov (United States)

    Zarate, Oscar A; Brody, Julia Green; Brown, Phil; Ramirez-Andreotta, Mónica D; Perovich, Laura; Matz, Jacob

    2016-01-01

    An individual's health, genetic, or environmental-exposure data, placed in an online repository, creates a valuable shared resource that can accelerate biomedical research and even open opportunities for crowd-sourcing discoveries by members of the public. But these data become "immortalized" in ways that may create lasting risk as well as benefit. Once shared on the Internet, the data are difficult or impossible to redact, and identities may be revealed by a process called data linkage, in which online data sets are matched to each other. Reidentification (re-ID), the process of associating an individual's name with data that were considered deidentified, poses risks such as insurance or employment discrimination, social stigma, and breach of the promises often made in informed-consent documents. At the same time, re-ID poses risks to researchers and indeed to the future of science, should re-ID end up undermining the trust and participation of potential research participants. The ethical challenges of online data sharing are heightened as so-called big data becomes an increasingly important research tool and driver of new research structures. Big data is shifting research to include large numbers of researchers and institutions as well as large numbers of participants providing diverse types of data, so the participants' consent relationship is no longer with a person or even a research institution. In addition, consent is further transformed because big data analysis often begins with descriptive inquiry and generation of a hypothesis, and the research questions cannot be clearly defined at the outset and may be unforeseeable over the long term. In this article, we consider how expanded data sharing poses new challenges, illustrated by genomics and the transition to new models of consent. We draw on the experiences of participants in an open data platform-the Personal Genome Project-to allow study participants to contribute their voices to inform ethical consent

  11. Separation and identification of differentially expressed nuclear matrix proteins between human esophageal immortalized and carcinomatous cell lines

    Institute of Scientific and Technical Information of China (English)

    Xing-Dong Xiong; En-Min Li; Li-Yan Xu; Hai-Bin Chen; Ling Chen; Wei-Jia Cai; Ya-Li Han; Zhong-Ying Shen; Yi Zeng

    2003-01-01

    AIM: To separate and identify differentially expressed nuclear matrix proteins (NMPs) between the immortalized human esophageal epithelial cell line (SHEE) and the malignantly transformed esophageal carcinoma cell line (SHEEC), and to provide new ways for finding specific markers and the pathogenesis of esophageal carcinoma.METHODS: SHEE and SHEEC cell lines were used to extract NMPs. The quality of NMPs was monitored by Western blot analysis including DNA topoisomerase Ⅱα, proliferation cell nuclear antigen (PCNA) and histone. NMPs of SHEE and SHEEC were analyzed by two-dimensional electrophoresis (2-DE), silver staining and PDQuest6.2 image analysis software. Three spots in which the differentially expressed NMlPs were more obvious, were selected and analyzed with matrix-assisted laser desorption/ionization time of flying mass spectrometry (MALDI- TOF-MS) and database search.RESULTS: Western blot analysis revealed that DNA topoisomerase Ⅱα and PCNA were detected, and the majority of histones were deleted in NMPs of SHEE and SHEEC. After 2-DE image analysis by PDQuest6.2 software, the 2-DE maps were detected with an average of 106±7.1 spots in SHEE and 132±5.0 spots in SHEEC. Most of them were matched one another (r=0.72), only 16 protein spots were found differing in intensity. Three NMPs including cytoskeletal tropomyosin,FK506bindingprotein6,similartoretinoblastoma binding protein 8 were preliminarily identified by MALDI- TOF-MS.CONCLUSION: These differentially expressed NMPs may play an important role during malignant transformation from SHEE to SHEEC. Their separation and identification will contribute to searching for specific markers and probing into the pathogenesis of esophageal carcinoma.

  12. Clinical features of familial adenomas polyps in Chinese and establishment of its immortal lymphocyte cell lines

    Institute of Scientific and Technical Information of China (English)

    Shan-Rong Cai; Su-Zhang Zhang; Shu Zheng

    2007-01-01

    AIM:To reserve the rare Chinese familial adenomas polyp (FAP) family resource and to investigate the clinical features of FAP in Chinese for its diagnosis.METHODS: Clinical features of patients with FAP were investigated. If there is any question, their medical records were verified. Blood sample was taken and lymphocyte immortal cell lines were established with modified EB-transformation methods. Congenital hypertrophy of retinal pigment epithelium (CHRPE) was checked by an experienced ophthalmologist.RESULTS: Twenty seven families including 21 classical FAP (CFAP) families, 3 attenuated FAP (AFAP) families,and 3 suspected AFAP families were investigated. A total of 116 lymphocyte immortal cell lines were established from 26 families. In all the FAP families, colorectal cancer occurred at the mean age of 42.84 years. Of the 16 families checked, 15 (93.75%) had CHRPE. The mean number of patients suffering from colorectal neoplasm was 3.14 in CFAP families and 2.0 in AFAP families (P < 0.01). The mean oldest age at diagnosis of FAP was 41.75 years in CFAP families, and 58.67 years in AFAP families, respectively (P < 0.01). Mean age of development of colorectal cancer was 42.23 in CFAP and 57.33 years old in AFAP (P < 0.01). Mean of the earliest age at diagnosis of FAP was 29.95 years in the FAP families with a positive family history and 46.80 years in the FAP families with a negative family history (P <0.01). The ratio of extra-intestinal tumors to colorectal neoplasms was different in the two kinds of families with positive and negative family history (P < 0.01).CONCLUSION: Additional use of ciclosporin will effectively improve to establish lymphocyte immortal cell lines with modified EB- transformation methods. In Chinese FAP, there was a high frequency of CHRPE, and a later age at diagnosis and a later age of development of colorectal cancer in AFAP. And earlier age at diagnosis in FAP with positive family history was also found that will help to

  13. Ephedra alte (joint pine): an invasive, problematic weedy species in forestry and fruit tree orchards in Jordan.

    Science.gov (United States)

    Qasem, Jamal R

    2012-01-01

    A field survey was carried out to record plant species climbed by Ephedra alte in certain parts of Jordan during 2008-2010. Forty species of shrubs, ornamental, fruit, and forest trees belonging to 24 plant families suffered from the climbing habit of E. alte. Growth of host plants was adversely affected by E. alte growth that extended over their vegetation. In addition to its possible competition for water and nutrients, the extensive growth it forms over host species prevents photosynthesis, smothers growth and makes plants die underneath the extensive cover. However, E. alte did not climb all plant species, indicating a host preference range. Damaged fruit trees included Amygdalus communis, Citrus aurantifolia, Ficus carica, Olea europaea, Opuntia ficus-indica, and Punica granatum. Forestry species that were adversely affected included Acacia cyanophylla, Ceratonia siliqua, Crataegus azarolus, Cupressus sempervirens, Pinus halepensis, Pistacia atlantica, Pistacia palaestina, Quercus coccifera, Quercus infectoria, Retama raetam, Rhamnus palaestina, Rhus tripartita, and Zizyphus spina-christi. Woody ornamentals attacked were Ailanthus altissima, Hedera helix, Jasminum fruticans, Jasminum grandiflorum, Nerium oleander, and Pyracantha coccinea. Results indicated that E. alte is a strong competitive for light and can completely smother plants supporting its growth. A. communis, F. carica, R. palaestina, and C. azarolus were most frequently attacked. PMID:22645486

  14. Cdk-dependent phosphorylation regulates TRF1 recruitment to PML bodies and promotes C-circle production in ALT cells.

    Science.gov (United States)

    Wilson, Florence R; Ho, Angus; Walker, John R; Zhu, Xu-Dong

    2016-07-01

    TRF1, a duplex telomeric DNA binding protein, is implicated in homologous-recombination-based alternative lengthening of telomeres, known as ALT. However, how TRF1 promotes ALT activity has yet to be fully characterized. Here we report that Cdk-dependent TRF1 phosphorylation on T371 acts as a switch to create a pool of TRF1, referred to as (pT371)TRF1, which is recruited to ALT-associated PML bodies (APBs) in S and G2 phases independently of its binding to telomeric DNA. We find that phosphorylation of T371 is essential for APB formation and C-circle production, both of which are hallmarks of ALT. We show that the interaction of (pT371)TRF1 with APBs is dependent upon ATM and homologous-recombination-promoting factors Mre11 and BRCA1. In addition, (pT371)TRF1 interaction with APBs is sensitive to transcription inhibition, which also reduces DNA damage at telomeres. Furthermore, overexpression of RNaseH1 impairs (pT371)TRF1 recruitment to APBs in the presence of campothecin, an inhibitor that prevents topoisomerase I from resolving RNA-DNA hybrids. These results suggest that transcription-associated DNA damage, perhaps arising from processing RNA-DNA hybrids at telomeres, triggers (pT371)TRF1 recruitment to APBs to facilitate ALT activity. PMID:27185864

  15. Ephedra alte (Joint Pine: An Invasive, Problematic Weedy Species in Forestry and Fruit Tree Orchards in Jordan

    Directory of Open Access Journals (Sweden)

    Jamal R. Qasem

    2012-01-01

    Full Text Available A field survey was carried out to record plant species climbed by Ephedra alte in certain parts of Jordan during 2008–2010. Forty species of shrubs, ornamental, fruit, and forest trees belonging to 24 plant families suffered from the climbing habit of E. alte. Growth of host plants was adversely affected by E. alte growth that extended over their vegetation. In addition to its possible competition for water and nutrients, the extensive growth it forms over host species prevents photosynthesis, smothers growth and makes plants die underneath the extensive cover. However, E. alte did not climb all plant species, indicating a host preference range. Damaged fruit trees included Amygdalus communis, Citrus aurantifolia, Ficus carica, Olea europaea, Opuntia ficus-indica, and Punica granatum. Forestry species that were adversely affected included Acacia cyanophylla, Ceratonia siliqua, Crataegus azarolus, Cupressus sempervirens, Pinus halepensis, Pistacia atlantica, Pistacia palaestina, Quercus coccifera, Quercus infectoria, Retama raetam, Rhamnus palaestina, Rhus tripartita, and Zizyphus spina-christi. Woody ornamentals attacked were Ailanthus altissima, Hedera helix, Jasminum fruticans, Jasminum grandiflorum, Nerium oleander, and Pyracantha coccinea. Results indicated that E. alte is a strong competitive for light and can completely smother plants supporting its growth. A. communis, F. carica, R. palaestina, and C. azarolus were most frequently attacked.

  16. Ephedra alte (joint pine): an invasive, problematic weedy species in forestry and fruit tree orchards in Jordan.

    Science.gov (United States)

    Qasem, Jamal R

    2012-01-01

    A field survey was carried out to record plant species climbed by Ephedra alte in certain parts of Jordan during 2008-2010. Forty species of shrubs, ornamental, fruit, and forest trees belonging to 24 plant families suffered from the climbing habit of E. alte. Growth of host plants was adversely affected by E. alte growth that extended over their vegetation. In addition to its possible competition for water and nutrients, the extensive growth it forms over host species prevents photosynthesis, smothers growth and makes plants die underneath the extensive cover. However, E. alte did not climb all plant species, indicating a host preference range. Damaged fruit trees included Amygdalus communis, Citrus aurantifolia, Ficus carica, Olea europaea, Opuntia ficus-indica, and Punica granatum. Forestry species that were adversely affected included Acacia cyanophylla, Ceratonia siliqua, Crataegus azarolus, Cupressus sempervirens, Pinus halepensis, Pistacia atlantica, Pistacia palaestina, Quercus coccifera, Quercus infectoria, Retama raetam, Rhamnus palaestina, Rhus tripartita, and Zizyphus spina-christi. Woody ornamentals attacked were Ailanthus altissima, Hedera helix, Jasminum fruticans, Jasminum grandiflorum, Nerium oleander, and Pyracantha coccinea. Results indicated that E. alte is a strong competitive for light and can completely smother plants supporting its growth. A. communis, F. carica, R. palaestina, and C. azarolus were most frequently attacked.

  17. Stepwise DNA Methylation Changes Are Linked to Escape from Defined Proliferation Barriers and Mammary Epithelial Cell Immortalization

    Energy Technology Data Exchange (ETDEWEB)

    Novak, Petr; Jensen, Taylor J.; Garbe, James C.; Stampfer, Martha R.; Futscher, Bernard W.

    2009-04-20

    The timing and progression of DNA methylation changes during carcinogenesis are not completely understood. To develop a timeline of aberrant DNA methylation events during malignant transformation, we analyzed genome-wide DNA methylation patterns in an isogenic human mammary epithelial cell (HMEC) culture model of transformation. To acquire immortality and malignancy, the cultured finite lifespan HMEC must overcome two distinct proliferation barriers. The first barrier, stasis, is mediated by the retinoblastoma protein and can be overcome by loss of p16(INK4A) expression. HMEC that escape stasis and continue to proliferate become genomically unstable before encountering a second more stringent proliferation barrier, telomere dysfunction due to telomere attrition. Rare cells that acquire telomerase expression may escape this barrier, become immortal, and develop further malignant properties. Our analysis of HMEC transitioning from finite lifespan to malignantly transformed showed that aberrant DNA methylation changes occur in a stepwise fashion early in the transformation process. The first aberrant DNA methylation step coincides with overcoming stasis, and results in few to hundreds of changes, depending on how stasis was overcome. A second step coincides with immortalization and results in hundreds of additional DNA methylation changes regardless of the immortalization pathway. A majority of these DNA methylation changes are also found in malignant breast cancer cells. These results show that large-scale epigenetic remodeling occurs in the earliest steps of mammary carcinogenesis, temporally links DNA methylation changes and overcoming cellular proliferation barriers, and provides a bank of potential epigenetic biomarkers that mayprove useful in breast cancer risk assessment.

  18. Development of Public Immortal Mapping Populations, Molecular Markers and Linkage Maps for Rapid Cycling Brassica rapa and B. oleracea

    Science.gov (United States)

    In this study we describe public immortal mapping populations of self-compatible lines, molecular markers, and linkage maps for Brassica rapa and B. oleracea. We propose that these resources are valuable reference tools for the Brassica community. The B. rapa population consists of 150 recombinant...

  19. Romidepsin reduces histone deacetylase activity, induces acetylation of histones, inhibits proliferation, and activates apoptosis in immortalized epithelial endometriotic cells.

    Science.gov (United States)

    Imesch, Patrick; Fink, Daniel; Fedier, André

    2010-12-01

    Romidepsin inhibited HDAC activity, produced acetylation of the histone proteins, up-regulated p21, and down-regulated cyclins B1 and D1, resulting in proliferation inhibition and apoptosis activation in 11z immortalized epithelial endometriotic cells. Our findings provide evidence that endometriotic cells are sensitive to the epigenetic effects of romidepsin and suggest that endometriosis may be therapeutically targeted by romidepsin.

  20. Twist-3 effect from the longitudinally polarized proton for ALT in hadron production from pp collisions

    Science.gov (United States)

    Koike, Yuji; Pitonyak, Daniel; Yoshida, Shinsuke

    2016-08-01

    We compute the contribution from the longitudinally polarized proton to the twist-3 double-spin asymmetry ALT in inclusive (light) hadron production from proton-proton collisions, i.e., p↑ p → → h X. We show that using the relevant QCD equation-of-motion relation and Lorentz invariance relation allows one to eliminate the twist-3 quark-gluon correlator (associated with the longitudinally polarized proton) in favor of one-variable twist-3 quark distributions and the (twist-2) transversity parton density. Including this result with the twist-3 pieces associated with the transversely polarized proton and unpolarized final-state hadron (which have already been calculated in the literature), we now have the complete leading-order cross section for this process.

  1. Twist-3 effect from the longitudinally polarized proton for ALT in hadron production from pp collisions

    Directory of Open Access Journals (Sweden)

    Yuji Koike

    2016-08-01

    Full Text Available We compute the contribution from the longitudinally polarized proton to the twist-3 double-spin asymmetry ALT in inclusive (light hadron production from proton–proton collisions, i.e., p↑p→→hX. We show that using the relevant QCD equation-of-motion relation and Lorentz invariance relation allows one to eliminate the twist-3 quark-gluon correlator (associated with the longitudinally polarized proton in favor of one-variable twist-3 quark distributions and the (twist-2 transversity parton density. Including this result with the twist-3 pieces associated with the transversely polarized proton and unpolarized final-state hadron (which have already been calculated in the literature, we now have the complete leading-order cross section for this process.

  2. De l’Illusion de l’altérité

    Directory of Open Access Journals (Sweden)

    Buata Malela

    2008-02-01

    Full Text Available Dans L’Illusion de l’altérité, Bernard Mouralis nous propose une synthèse significative des études littéraires francophones d’Afrique. Son ouvrage rassemble près de quarante années de recherches et de réflexions sur ce qu’il appelle les littératures « négro-africaines ». Il offre une vision claire des progressions multiples de ces recherches, ce qui contribue à faire de ce livre un outil de référence pour se familiariser avec certaines thématiques et questions liées aux études littéraires d’A...

  3. Nuclear-receptor-mediated telomere insertion leads to genome instability in ALT cancers.

    Science.gov (United States)

    Marzec, Paulina; Armenise, Claudia; Pérot, Gaëlle; Roumelioti, Fani-Marlen; Basyuk, Eugenia; Gagos, Sarantis; Chibon, Frédéric; Déjardin, Jérôme

    2015-02-26

    The breakage-fusion-bridge cycle is a classical mechanism of telomere-driven genome instability in which dysfunctional telomeres are fused to other chromosomal extremities, creating dicentric chromosomes that eventually break at mitosis. Here, we uncover a distinct pathway of telomere-driven genome instability, specifically occurring in cells that maintain telomeres with the alternative lengthening of telomeres mechanism. We show that, in these cells, telomeric DNA is added to multiple discrete sites throughout the genome, corresponding to regions regulated by NR2C/F transcription factors. These proteins drive local telomere DNA addition by recruiting telomeric chromatin. This mechanism, which we name targeted telomere insertion (TTI), generates potential common fragile sites that destabilize the genome. We propose that TTI driven by NR2C/F proteins contributes to the formation of complex karyotypes in ALT tumors. PMID:25723166

  4. Incontri di Fisica delle Alte Energie Italian Meeting on High Energy Physics Napoli

    CERN Document Server

    Carlino, Gianpaolo; Merola, Leonardo; Paolucci, Pierluigi; Ricciardi, Giulia; IFAE 2007

    2008-01-01

    This book collects the Proceedings of the Workshop "Incontri di Fisica delle Alte Energie (IFAE) 2007, Napoli, 11-13 April 2007". This is the sixth edition of a series of meetings on fundamental research in particle physics and was attended by about 160 researchers. Presentations, both theoretical and experimental, addressed the status of Physics of the Standard Model and beyond, Flavour phyisc, Neutrino and Astroparticle physics, new technology in high energy physics. Special emphasis was given to the expectations of the forthcoming Large Hadron Collider, due in operation at the end of 2007. The venue of plenary sessions interleaved with parallel ones allowed for a rich exchange of ideas, presented in these Proceedings, that form a coherent picture of the findings and of the open questions in this extremely challenging cultural field. The venue of plenary sessions interleaved with parallel ones allowed for a rich exchange of ideas, presented in these Proceedings, that form a coherent picture of the findings ...

  5. 电影《Immortal Beloved》中交响曲音乐赏析

    Institute of Scientific and Technical Information of China (English)

    张志敏

    2011-01-01

    电影《Immortal Beloved》是1994年拍摄的一部关于贝多芬的传记电影.影片自始至终贯串了贝多芬作品的旋律,如按图索骥,便能深入贝多芬令人动容的音乐世界,同时也能领略到贝多芬每部作品如何成功地扮演推展剧情的说书人的功能.透过交响曲严肃而深奥的外表,发现其平易近人的本质与深刻的内涵.

  6. The use of hTERT-immortalized cells in tissue engineering

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Abdallah, Basem; Yu, Zentao;

    2004-01-01

    The use of human telomerase reverse transcriptase (hTERT)-immortalized cells in tissue engineering protocols is a potentially important application of telomere biology. Several human cell types have been created that overexpress the hTERT gene with enhanced telomerase activity, extended life span...... and maintained or even improved functional activities. Furthermore, some studies have employed the telomerized cells in tissue engineering protocols with very good results. However, high telomerase activity allows extensive cell proliferation that may be associated with genomic instability and risk for cell...... transformation. Thus, safety issues should be studied carefully before using the telomerized tissues in the clinic. Alternatively, the development of conditional or intermittent telomerase activation protocols is needed....

  7. Recovery of important physiological functions in 3D culture of immortal hepatocytes

    DEFF Research Database (Denmark)

    Wrzesinski, Krzysztof; Fey, S. J.

    2011-01-01

    hepatocytes using the classical approaches (in “2D”) and using a system which leads to the generation of spheroids of cells held in suspension (“3D”). Both approaches gave rise to cultures where the large majority of cells were viable, produced similar amounts of ATP, incorporated similar amounts......It is widely expected that cells grown in 3D environments (in suspension, on scaffolds etc.) will be superior to growing cells in classical 2D culture flasks. These expectations include the belief that cells grown in 3D culture will possess physiological characteristics that resemble more closely...... to grow human liver cells in ‘3 dimensional’ cultures so that they behave very similar to the liver in our bodies. By growing the immortal hepatocytes in specially designed bioreactors they form small pieces of ‘pseudotissue’ which exhibit several of the functions seen in the adult liver. We have grown...

  8. Immortalization and characterization of mouse floxed Bmp2/4 osteoblasts

    International Nuclear Information System (INIS)

    Generation of a floxed Bmp2/4 osteoblast cell line is a valuable tool for studying the modulatory effects of Bmp2 and Bmp4 on osteoblast differentiation as well as relevant molecular events. In this study, primary floxed Bmp2/4 mouse osteoblasts were cultured and transfected with simian virus 40 large T-antigen. Transfection was verified by polymerase chain reaction (PCR) and immunohistochemistry. To examine the characteristics of the transfected cells, morphology, proliferation and mineralization were analyzed, expression of cell-specific genes including Runx2, ATF4, Dlx3, Osx, dentin matrix protein 1, bone sialoprotein, osteopontin, osteocalcin, osteonectin and collagen type I was detected. These results show that transfected floxed Bmp2/4 osteoblasts bypassed senescence with a higher proliferation rate, but retain the genotypic and phenotypic characteristics similar to the primary cells. Thus, we for the first time demonstrate the establishment of an immortalized mouse floxed Bmp2/4 osteoblast cell line.

  9. Anti-melanogenic effects of black, green, and white tea extracts on immortalized melanocytes.

    Science.gov (United States)

    Kim, Young Chul; Choi, So Young; Park, Eun Ye

    2015-01-01

    Tea contains polyphenols and is one of the most popular beverages consumed worldwide. Because most tyrosinase inhibitors that regulate melanogenesis are phenol/catechol derivatives, this study investigated the inhibitory effects of Camellia sinensis water extracts (CSWEs), including black tea, green tea, and white tea extracts, on melanogenesis using immortalized melanocytes. CSWEs inhibited melanin accumulation and melanin synthesis along with tyrosinase activity in a concentration-dependent manner. These inhibitory effects were superior to those of arbutin, a well-known depigmenting agent. The anti-melanogenic activity of black (fermented) tea was higher than that of a predominant tea catecholamine, epigallocatechin gallate. CSWEs, especially black tea extract, decreased tyrosinase protein levels in a concentration-dependent manner. These results suggest that the anti-melanogenic effect of CSWEs is mediated by a decrease in both tyrosinase activity and protein expression, and may be augmented by fermentation. Thus, CSWEs could be useful skin-whitening agents in the cosmetic industry. PMID:25643794

  10. Immortalization and characterization of mouse floxed Bmp2/4 osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Li-An [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi-an (China); Yuan, Guohua; Yang, Guobin [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Key Laboratory of Oral Biomedical Engineering Ministry of Education, Wuhan (China); Ortiz-Gonzalez, Iris [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Yang, Wuchen; Cui, Yong [Department of Periodontics, Dental School, The University of Texas Health Science Center at San Antonio, TX (United States); MacDougall, Mary [Department of Oral/Maxillofacial Surgery, University of Alabama, Birmingham, AL (United States); Donly, Kevin J. [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Harris, Stephen [Department of Periodontics, Dental School, The University of Texas Health Science Center at San Antonio, TX (United States); Chen, Shuo, E-mail: chens0@uthscsa.edu [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States)

    2009-08-14

    Generation of a floxed Bmp2/4 osteoblast cell line is a valuable tool for studying the modulatory effects of Bmp2 and Bmp4 on osteoblast differentiation as well as relevant molecular events. In this study, primary floxed Bmp2/4 mouse osteoblasts were cultured and transfected with simian virus 40 large T-antigen. Transfection was verified by polymerase chain reaction (PCR) and immunohistochemistry. To examine the characteristics of the transfected cells, morphology, proliferation and mineralization were analyzed, expression of cell-specific genes including Runx2, ATF4, Dlx3, Osx, dentin matrix protein 1, bone sialoprotein, osteopontin, osteocalcin, osteonectin and collagen type I was detected. These results show that transfected floxed Bmp2/4 osteoblasts bypassed senescence with a higher proliferation rate, but retain the genotypic and phenotypic characteristics similar to the primary cells. Thus, we for the first time demonstrate the establishment of an immortalized mouse floxed Bmp2/4 osteoblast cell line.

  11. Anti-melanogenic effects of black, green, and white tea extracts on immortalized melanocytes.

    Science.gov (United States)

    Kim, Young Chul; Choi, So Young; Park, Eun Ye

    2015-01-01

    Tea contains polyphenols and is one of the most popular beverages consumed worldwide. Because most tyrosinase inhibitors that regulate melanogenesis are phenol/catechol derivatives, this study investigated the inhibitory effects of Camellia sinensis water extracts (CSWEs), including black tea, green tea, and white tea extracts, on melanogenesis using immortalized melanocytes. CSWEs inhibited melanin accumulation and melanin synthesis along with tyrosinase activity in a concentration-dependent manner. These inhibitory effects were superior to those of arbutin, a well-known depigmenting agent. The anti-melanogenic activity of black (fermented) tea was higher than that of a predominant tea catecholamine, epigallocatechin gallate. CSWEs, especially black tea extract, decreased tyrosinase protein levels in a concentration-dependent manner. These results suggest that the anti-melanogenic effect of CSWEs is mediated by a decrease in both tyrosinase activity and protein expression, and may be augmented by fermentation. Thus, CSWEs could be useful skin-whitening agents in the cosmetic industry.

  12. Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells.

    Science.gov (United States)

    Severson, Paul L; Vrba, Lukas; Stampfer, Martha R; Futscher, Bernard W

    2014-12-01

    Genetic mutations are known to drive cancer progression and certain tumors have mutation signatures that reflect exposures to environmental carcinogens. Benzo[a]pyrene (BaP) has a known mutation signature and has proven capable of inducing changes to DNA sequence that drives normal pre-stasis human mammary epithelial cells (HMEC) past a first tumor suppressor barrier (stasis) and toward immortality. We analyzed normal, pre-stasis HMEC, three independent BaP-derived post-stasis HMEC strains (184Aa, 184Be, 184Ce) and two of their immortal derivatives(184A1 and 184BE1) by whole exome sequencing. The independent post-stasis strains exhibited between 93 and 233 BaP-induced mutations in exons. Seventy percent of the mutations were C:G>A:T transversions, consistent with the known mutation spectrum of BaP. Mutations predicted to impact protein function occurred in several known and putative cancer drivers including p16, PLCG1, MED12, TAF1 in 184Aa; PIK3CG, HSP90AB1, WHSC1L1, LCP1 in 184Be and FANCA, LPP in 184Ce. Biological processes that typically harbor cancer driver mutations such as cell cycle, regulation of cell death and proliferation, RNA processing, chromatin modification and DNA repair were found to have mutations predicted to impact function in each of the post-stasis strains. Spontaneously immortalized HMEC lines derived from two of the BaP-derived post-stasis strains shared greater than 95% of their BaP-induced mutations with their precursor cells. These immortal HMEC had 10 or fewer additional point mutations relative to their post-stasis precursors, but acquired chromosomal anomalies during immortalization that arose independent of BaP. The results of this study indicate that acute exposures of HMEC to high dose BaP recapitulate mutation patterns of human tumors and can induce mutations in a number of cancer driver genes. PMID:25435355

  13. Establishment and characterization of a rat pancreatic stellate cell line by spontaneous immortalization

    Institute of Scientific and Technical Information of China (English)

    Atsushi Masamune; Masahiro Satoh; Kazuhiro Kikuta; Noriaki Suzuki; Tooru Shimosegawa

    2003-01-01

    AIM: Activated pancreatic stellate cells (PSCs) have been implicated in the pathogenesis of pancreatic fibrosis and inflammation. Primary PSCs can be subcultured only several times because of their limited growth potential. A continuous cell line may therefore be valuable in studying molecular mechanisms of these pancreatic disorders. The aim of this study was to establish a cell line of rat PSCs by spontaneous immortalization.METHODS: PSCs were isolated from the pancreas of male Wistar rats, and conventional subcultivation was performed repeatedly. Telomerase activity was measured using the telomere repeat amplification protocol. Activation of transcription factors was assessed by electrophoretic mobility shift assay.Activation of mitogen-activated protein (MAP) kinases was examined by Western blotting using anti-phosphospecific antibodies. Expression of cytokine-induced neutrophil chemoattractant-1 was determined by enzyme immunoassay.RESULTS: Conventional subcultivation yielded actively growing cells. One clone was obtained after limiting dilution,and designated as SIPS. This cell line has been passaged repeatedly more than 2 years, and is thus likely immortalized.SIPS cells retained morphological characteristics of primary,culture-activated PSCs. SIPS expressed α-smooth muscle actin, glial acidic fibrillary protein, vimentin, desmin, type Ⅰ collagen, fibronectin, and prolyl hydroxylases. Telomerase activity and p53 expression were negative. Proliferation of SIPS cells was serum-dependent, and stimulated with platelet-derived growth factor-BB through the activation of extracellular signal-regulated kinase. Interleukin-1β activated nuclear factor-κB, activator protein-1, and MAP kinases.Interleukin-1β induced cytokine-induced neutrophil chemoattractant-1 expression through the activation of nuclear factor-κB and MAP kinases.CONCLUSION: SIPS cells can be useful for in vitro studies of cell biology and signal transduction of PSCs.

  14. Microarray analyses and molecular profiling of steatosis induction in immortalized human hepatocytes.

    Science.gov (United States)

    De Gottardi, Andrea; Vinciguerra, Manlio; Sgroi, Antonino; Moukil, Moulay; Ravier-Dall'Antonia, Florence; Pazienza, Valerio; Pugnale, Paolo; Foti, Michelangelo; Hadengue, Antoine

    2007-08-01

    Hepatic steatosis is an important risk factor for the development of inflammation, fibrosis and impaired liver regeneration. The factors regulating lipid accumulation and driving hepatic steatosis toward inflammation, fibrosis and impaired regeneration are largely unknown. The aim of this study was to identify major alterations in gene expression occurring in steatotic hepatocytes, and to analyze how these changes impact cellular processes associated with steatosis. Microarray gene chips and RT-PCR were performed to analyze changes in gene expression induced in fatty human immortalized hepatocytes after treatment with 50 muM oleic acid for 7 days. Lipid metabolism and triglyceride accumulation in these cells was examined by Oil-Red-O staining, thin-layer chromatography (TLC) and immunofluorescence. Caspase 3 activity, BrdU incorporation and trypan blue exclusion were used to study apoptosis, proliferation and cell viability. Finally, quantitative analysis of signalling induced by insulin was performed by Western blot. Characterization of steatosis in three hepatocyte-derived cell lines indicated that the immortalized human hepatocytes (IHH) line was the most appropriate cell line for this study. Gene expression analysis showed significant alterations in the transcription of two major classes of genes involved either in cholesterol and fatty acid biosynthesis, as well as lipid export, or in apoptosis and cell proliferation. Such changes were functionally relevant, since TLC indicated that synthesis and accumulation of triglycerides were increased in steatotic cells, while synthesis of cholesterol and fatty acids were decreased. Lipid accumulation in IHH was associated with an increased apoptosis and an inhibition of cell proliferation and viability. No detectable changes in genes associated with insulin resistance were observed in steatotic cells, but signalling induced by insulin was more efficient in steatotic IHH as compared to control cells. We conclude that IHH

  15. The G-Quadruplex Ligand Telomestatin Impairs Binding of Topoisomerase IIIα to G-Quadruplex-Forming Oligonucleotides and Uncaps Telomeres in ALT Cells

    OpenAIRE

    Nassima Temime-Smaali; Lionel Guittat; Assitan Sidibe; Kazuo Shin-ya; Chantal Trentesaux; Jean-François Riou

    2009-01-01

    In Alternative Lengthening of Telomeres (ALT) cell lines, specific nuclear bodies called APBs (ALT-associated PML bodies) concentrate telomeric DNA, shelterin components and recombination factors associated with telomere recombination. Topoisomerase IIIalpha (Topo III) is an essential telomeric-associated factor in ALT cells. We show here that the binding of Topo III to telomeric G-overhang is modulated by G-quadruplex formation. Topo III binding to G-quadruplex-forming oligonucleotides was s...

  16. An ALMT1 gene cluster controlling aluminium (aluminum) tolerance at the Alt4 locus of rye (Secale cereale L.)

    Science.gov (United States)

    Aluminium toxicity is a major problem in agriculture worldwide. Among the cultivated triticeae, rye (Secale cereale L.) is one of the most Al-tolerant and represents an important potential source of Al-tolerance for improvement of wheat. The Alt4 Al-tolerance locus of rye contains a cluster of genes...

  17. Optical characterisation of poly-2,5-diheptyl-1,4-phenylene-alt-2,5-thienylene

    NARCIS (Netherlands)

    Loi, M.A.; List, E.J.W.; Gadermaier, C.; Graupner, W.; Leising, G.; Bongiovanni, G.; Mura, A.; Pireaux, J.-J.; Kaeriyama, K.

    2000-01-01

    We have investigated the electronic properties and the photoluminescence (PL) decay of the poly-2,5-diheptyl-1,4-phenylene-alt-2,5-thienylene (PDHPT) copolymer made up by the regular alternation of high and low band-gap units. Experimental data show that the large twisting of the neighbouring consti

  18. Kas erivajadustega lapsed saavad õigel ajal abi? / Ene Mägi, Urve Raudsepp-Alt, Ale Sprenk, Peeter Aas

    Index Scriptorium Estoniae

    2009-01-01

    Küsimusele vastavad: Tallinna Ülikooli Kasvatusteaduste Instituudi eri- ja sotsiaalpedagoogika osakonna juhataja Ene Mägi, Tallinna Haridusameti üldhariduse osakonna peaspetsialist Urve Raudsepp-Alt, Krabi põhikooli direktor Ale Sprenk, Põlva Maavalitsuse haridus-, kultuuri- ja sotsiaalosakonna juhataja Peeter Aas

  19. Liver enzymes: interaction analysis of smoking with alcohol consumption or BMI, comparing AST and ALT to γ-GT.

    Directory of Open Access Journals (Sweden)

    Lutz P Breitling

    Full Text Available BACKGROUND: A detrimental interaction between smoking and alcohol consumption with respect serum γ-glutamyltransferase (γ-GT has recently been described. The underlying mechanisms remain unknown. The present work aimed to provide further insights by examining similar interactions pertaining to aspartate and alanine transaminase (AST, ALT, routine liver markers less prone to enzyme induction. METHODOLOGY/PRINCIPAL FINDINGS: The present cross-sectional analysis was based on records from routine occupational health examinations of 15,281 male employees predominantly of the construction industry, conducted from 1986 to 1992 in Southern Germany. Associations of smoking intensity with log-transformed activities of γ-GT, AST, and ALT were examined in regression models adjusted for potential confounders and including an interaction of smoking with alcohol consumption or body mass index (BMI. Statistically significant interactions of smoking were observed with both alcohol consumption (AST and ALT, each with P<0.0001 and BMI (AST only, P<0.0001. The interactions all were in the same directions as for γ-GT, i.e. synergistic with alcohol and opposite with BMI. CONCLUSION: The patterns of interaction between smoking and alcohol consumption or BMI with respect to AST and ALT resembled those observed for γ-GT. This renders enzyme induction a less probable mechanism for these associations, whereas it might implicate exacerbated hepatocellular vulnerability and injury.

  20. Influence of the degree of hydrolysis of poly(styrene-alt-maleic anhydride) on miscibility with poly(vinyl acetate)

    NARCIS (Netherlands)

    Bosma, M.; Vorenkamp, E.J.; Brinke, G. ten; Challa, G.

    1988-01-01

    The influence of the hydrolysis of anhydride groups in poly(styrene-alt-maleic anhydride) (PSMA) on its miscibility with poly(vinyl acetate) (PVAc) is investigated. The cloudpoint curves of these blends are determined as a function of the degree of hydrolysis. The miscibility is shown to improve wit

  1. Study on the Correlation of Plasma NO, ET-1 and ALT in the Patients with Chronic Hepatitis and Cirrhosis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The levels of plasma nitric oxide (NO), endothelin-1 (ET-1) and ALT in the patients with chronic hepatitis B and active cirrhosis and the correlation among them were observed and analyzed. NO3- was restored by using cadmium column assay and NO2- measured by heavy nitrogen assay. The primitive NO3- and total restored NO2-(NO3-/ NO2-) in plasma of the patients with chronic hepatitis and cirrhosis. Plasma ET-1 and ALT levels were determined by using radioimmunological assay and Lai's assay, respectively. Compared with normal control group, the plasma levels of NO2-/NO3- and ET-1 in the patients with chronic active hepatitis and active cirrhosis were significantly increased (P<0.05-0.01). There was a positive correlation between NO and ALT, and ET-1 and ALT in the patients with chronic active hepatitis and active cirrhosis respectively. It was suggested that elevation of both NO and ET-1 levels were closely related with injury severity of liver function.

  2. The effect of IFN-based therapies on the short-term dynamics of alt in HCV-infected patients

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, R. M. (Ruy M.); Talal, A. H. (Andrew H.); Layden, J. E. (Jennifer E.); Powers, K. A. (Kimberly A.); Layden, T. J. (Thomas J.); Perelson, Alan S.,

    2002-01-01

    IFN therapy of HCV-infection has been shown to reduce production of virus from infected cells, but its effect on hepatocytes is less well understood. One indicator of liver damage is ALT, which has been used as an associated diagnostic for HCV infection.

  3. Naised käsu korras firmade juhatusse! Jah või ei? / Kairi Alt, Aveli Kippari, Karl Koort... [jt.

    Index Scriptorium Estoniae

    2011-01-01

    Küsimusele vastavad Columbus IT Partner Eesti AS personalijuht Kairi Alt, Stele ja Riveli omanik Aveli Kippari, AS Panaviatic'i turundusjuht Karl Koort, OÜ Tarkvara Tehnoloogia Arenduskeskuse tegevjuht Indrek Vainu, AS PricewaterhouseCoopers auditiosakonna direktor Eva Jansen, Kalev Chocolate Factory tootmisjuht Hardo Reinike

  4. Comparative proteomic analysis of primary schwann cells and a spontaneously immortalized schwann cell line RSC 96: a comprehensive overview with a focus on cell adhesion and migration related proteins.

    Science.gov (United States)

    Ji, Yuhua; Shen, Mi; Wang, Xin; Zhang, Shuqiang; Yu, Shu; Chen, Gang; Gu, Xiaosong; Ding, Fei

    2012-06-01

    Schwann cells (SCs) are the principal glial cells of the peripheral nervous system (PNS). As a result of tissue heterogeneity and difficulties in the isolation and culture of primary SCs, a considerable understanding of SC biology is obtained from SC lines. However, the differences between the primary SCs and SC lines remain uncertain. In the present study, quantitative proteomic analysis based on isobaric tags for relative and absolute quantitation (iTRAQ) labeling was conducted to obtain an unbiased view of the proteomic profiles of primary rat SCs and RSC96, a spontaneously immortalized rat SC line. Out of 1757 identified proteins (FDR RSC96. Bioinformatics analysis indicated the unique features of spontaneous immortalization, illustrated the dedifferentiated state of RSC96, and highlighted a panel of novel proteins associated with cell adhesion and migration including CADM4, FERMT2, and MCAM. Selected proteomic data and the requirement of these novel proteins in SC adhesion and migration were properly validated. Taken together, our data collectively revealed proteome differences between primary SCs and RSC96, validated several differentially expressed proteins with potential biological significance, and generated a database that may serve as a useful resource for studies of SC biology and pathology.

  5. Structure of Poly(styrene-b-ethylene-alt-propylene) Diblock Copolymer Micelles in Squalane

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Soo-Hyung; Bates, Frank S.; Lodge, Timothy P.; (UMM)

    2009-11-04

    The temperature dependence of the micellar structures formed by poly(styrene-b-ethylene-alt-propylene) (SEP) diblock copolymers in squalane, a highly selective solvent for the PEP blocks, has been studied using dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Four SEP diblock copolymers were prepared by sequential anionic polymerization of styrene and isoprene, followed by hydrogenation of the isoprene blocks, to yield SEP(17-73), SEP(26-66), SEP(36-69), and SEP(42-60), where the numbers indicate block molecular weights in kDa. All four polymers formed well-defined spherical micelles. In dilute solution, DLS provided the temperature-dependent mean hydrodynamic radius, R{sub h}, and its distribution, while detailed fitting of the SAXS profiles gave the core radius, R{sub c}, the equivalent hard sphere radius, R{sub hs}, and an estimate of the aggregation number, N{sub agg}. In general, the micelles became smaller as the critical micelle temperature (CMT) was approached, which was well above the glass transition of the core block. As concentration increased the micelles packed onto body centered cubic lattices for all four copolymers, which underwent order-disorder transitions upon heating near the dilute solution CMTs. The results are discussed in terms of current understanding of block copolymer solution self-assembly, and particular attention is paid to the issue of equilibration, given the high glass transition temperature of the core block.

  6. Structure of poly(styrene-b-ethylene-alt-propylene) diblock copolymer micelles in squalane.

    Science.gov (United States)

    Choi, Soo-Hyung; Bates, Frank S; Lodge, Timothy P

    2009-10-22

    The temperature dependence of the micellar structures formed by poly(styrene-b-ethylene-alt-propylene) (SEP) diblock copolymers in squalane, a highly selective solvent for the PEP blocks, has been studied using dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Four SEP diblock copolymers were prepared by sequential anionic polymerization of styrene and isoprene, followed by hydrogenation of the isoprene blocks, to yield SEP(17-73), SEP(26-66), SEP(36-69), and SEP(42-60), where the numbers indicate block molecular weights in kDa. All four polymers formed well-defined spherical micelles. In dilute solution, DLS provided the temperature-dependent mean hydrodynamic radius, R(h), and its distribution, while detailed fitting of the SAXS profiles gave the core radius, R(c), the equivalent hard sphere radius, R(hs), and an estimate of the aggregation number, N(agg). In general, the micelles became smaller as the critical micelle temperature (CMT) was approached, which was well above the glass transition of the core block. As concentration increased the micelles packed onto body centered cubic lattices for all four copolymers, which underwent order-disorder transitions upon heating near the dilute solution CMTs. The results are discussed in terms of current understanding of block copolymer solution self-assembly, and particular attention is paid to the issue of equilibration, given the high glass transition temperature of the core block.

  7. The photophysical properties and morphology of fluorene-alt-benzene based conjugated polymer

    Institute of Scientific and Technical Information of China (English)

    Yang Guizhong; Wang Min; Liu Tianxi

    2006-01-01

    A series of fluorene-alt-benzene based conjugated main chain polymers chemically attached with alkyl side chains of different lengths on phenylene rings were designed and synthesized by a palladium catalyzed Suzuki coupling reaction.The UV-vis absorption and fluorescence spectra,thermal stability of spectral property,phase transition behavior and morphology of the synthesized polymers were investigated.With increasing the length of the alkyl side chain,the UV and fluorescence spectra exhibit an obvious blue shift compared with those of the unsubstituted polymer.The alkyl substitution improves the thermal spectral stability of the polymers due to the steric hindrance of the alkyl side chains,thus leading to efficient separation of the main chain backbones.The phase transition behavior is closely related to the length of the alkyl side chains attached on the phenylene rings.The annealed films of the polymers display characteristic nematic liquid crystalline texture.TEM observations indicate that solvent-cast thin deposits of all the polymers show typical fibritlar morphology.

  8. Flexible Polyimide Aerogel Cross-linked by Poly(maleic Anhydride-alt-alkylene)

    Science.gov (United States)

    Guo, Haiquan; Meador, Mary Ann B.; Wilkewitz, Brittany Marie

    2014-01-01

    Aerogels are potential materials for aerospace applications due to their lower thermal conductivity, lighter weight, and low dielectric constant. However, silica aerogels are restricted due to their inherent fragility, hygroscopic nature, and poor mechanical properties, especially in extreme aerospace environments. In order to fit the needs of aerospace applications, developing new thermal insulation materials that are flexible, and moisture resistant is needed. To this end, we fabricated a series of polyimide aerogels crosslinked with different poly(maleic anhydride-alt-alkylene)s as seen in Scheme 1. The polyimide oligomers were made with 3,3,4,4-biphenyltetracarboxylic dianhydride (BPDA), and different diamines or diamine combinations. The resulting aerogels have low density (0.06 gcm3 to 0.16 gcm3) and high surface area (240-440 m2g). The effect of the different backbone structures on density, shrinkage, porosity, surface area, mechanical properties, moisture resistance and thermal properties will be discussed. These novel polyalkylene-imide aerogels may be potential candidates for applications such as space suit insulation for planetary surface missions, insulation for inflatable structures for habitats, inflatable aerodynamic decelerators for entry, descent and landing (EDL) operations, and cryotank insulation for advance space propulsion systems. Scheme 1. Network of polyimide aerogels crosslinked with deifferent poly(maleic anhydride).

  9. EXPERIMENTAL STUDY OF THE DIFFERENTIATION HPV16 SUBGENES-IMMORTALIZED HUMAN ENDOCERVICAL CELLS INDUCED BY ALL-TRANS-RETINOIC ACID

    Institute of Scientific and Technical Information of China (English)

    LI Yi-ming; ZHAO Yong; LIN Xiao

    2005-01-01

    Objective: To investigate the differentiation-inducing effects of all-trans-retinoic (ATRA) to HPV16 subgenesimmortalized human endocervical cells (H8 cell) in vitro. Methods: HPV16 subgenes-immortalized human endocervical cells(H8 cells) were cultured in vitro. After treated with ATRA, the proliferation of immortalized human endocervical cells was measured by MTT assay; morphological changes were observed using M and TEM; cell cycle was analyzed by FCM;expression of Ki67 was tested using immunocytochemistry and the activity of telomerase was tested using PCR-ELISA.Results: ATRA could inhibit proliferation of H8 cells significantly and induce their morphodifferentiation. According to FCM, H8 cells accumulated in G1 phase and expression of Ki67 and activity of telomerase reduced significantly after treatment with ATRA. Conclusion: ATRA could induce the differentiation of H8 cell line obviously, which might be achieved by inhibiting proliferation, blocking cell cycle, and reducing activity of telomerase.

  10. HPV16 E7 protein and hTERT proteins defective for telomere maintenance cooperate to immortalize human keratinocytes.

    Directory of Open Access Journals (Sweden)

    Jonathan Miller

    Full Text Available Previous studies have shown that wild-type human telomerase reverse transcriptase (hTERT protein can functionally replace the human papillomavirus type 16 (HPV-16 E6 protein, which cooperates with the viral E7 protein in the immortalization of primary keratinocytes. In the current study, we made the surprising finding that catalytically inactive hTERT (hTERT-D868A, elongation-defective hTERT (hTERT-HA, and telomere recruitment-defective hTERT (hTERT N+T also cooperate with E7 in mediating bypass of the senescence blockade and effecting cell immortalization. This suggests that hTERT has activities independent of its telomere maintenance functions that mediate transit across this restriction point. Since hTERT has been shown to have a role in gene activation, we performed microarray studies and discovered that E6, hTERT and mutant hTERT proteins altered the expression of highly overlapping sets of cellular genes. Most important, the E6 and hTERT proteins induced mRNA and protein levels of Bmi1, the core subunit of the Polycomb Group (PcG complex 1. We show further that Bmi1 substitutes for E6 or hTERT in cell immortalization. Finally, tissue array studies demonstrated that expression of Bmi1 increased with the severity of cervical dysplasia, suggesting a potential role in the progression of cervical cancer. Together, these data demonstrate that hTERT has extra-telomeric activities that facilitate cell immortalization and that its induction of Bmi1 is one potential mechanism for mediating this activity.

  11. Quantitation of telomerase components and hTERT mRNA splicing patterns in immortal human cells

    OpenAIRE

    Yi, Xiaoming; Jerry W Shay; Wright, Woodring E.

    2001-01-01

    Telomerase is a reverse transcriptase that adds telomeric repeats to chromosomal ends. In most normal human somatic cells, telomerase is repressed and telomeres progressively shorten, leading to limited proliferative life-span. Telomerase reactivation is associated with cellular immortalization and is a frequent event during tumorigenesis. The telomerase ribonucleoprotein complex consists of two essential components, a catalytic protein subunit [human telomerase reverse transcriptase (hTERT)]...

  12. Terror management theory and the impact of individual and collective mortality salience on symbolic and literal immortality beliefs

    OpenAIRE

    Conrad, Brent

    2009-01-01

    According to Terror Management Theory (TMT), many human behaviors, attitudes, and thoughts are the result of an attempt to reduce the uncomfortable feelings associated with the knowledge that human life is finite. Although many of TMT’s postulates have been supported by research, the assumption that an underlying desire for literal or symbolic immortality is partly responsible for mortality salience responses has received less research attention. Additionally, there has been little research i...

  13. Immortal Ring-Opening Polymerization of rac-Lactide Using Polymeric Alcohol as Initiator to Prepare Graft Copolymer

    OpenAIRE

    Na Liu; Bo Liu; Changguang Yao; Dongmei Cui

    2016-01-01

    In the presence of a small molecular protic initiator, immortal ring-opening polymerization (ROP) of lactide (LA) is a highly efficient strategy to synthesize polylactide in a controllable manner, while using polymeric alcohol as an initiator has been less investigated. A series of polymeric alcohols (PS–OH) composed of styrene and 4.3%–18% hydroxyl functional styrene (diethyl(hydroxy(4-vinylphenyl)methyl)phosphonate, St–OH) were synthesized through reversible addition-fragmentation transfer ...

  14. Immortalization of human umbilical vein endothelial cells with telomerase reverse transcriptase and simian virus 40 large T antigen

    Institute of Scientific and Technical Information of China (English)

    BIAN Chang; ZHAO Kui; TONG Guo-xin; ZHU Yong-liang; CHEN Peng

    2005-01-01

    Objective: To establish normally conditionally-immortalized human umbilical vein endothelial cells (HUVECs) by ectopic expression of the human telomerase catalytic enzyme (hTERT) and simian virus 40 large T (SV40 LT) antigen. Methods:Primary HUVECs were transfected with recombinant retrovirus containing hTERT or SV40 LT respectively. Subsequently drug resistant cell clones were screened and expanded for further studies. Endothelial cell biomarkers were confirmed by examination.Results: The morphological phenotype of the transfected cells was similar to the non-transfected cells. Von Willebrand factor,hTERT and SV40 LT could be detected in transfected HUVECs. Moreover, higher telomerase activity in transfected cells was maintained for over 50 population doublings compared with only low level of endogenous telomerase transiently at early population doublings in primary HUVECs. When exposed to TNF-α (tumor necrosis factor-α), the expression of E-selectin in transfected cells was significantly up-regulated, but no alteration of endothelial lipase was found. Conclusion: Ectopic coexpression of hTERT and SV40 LT can effectively immortalize HUVECs without tumorigenicity in vitro. Immortalized HUVECs may be an ideal target of further molecular function studies.

  15. Establishment of immortalized B lymphoblastoid cell lines of old residents in high background radiation area in Guangdong, China

    International Nuclear Information System (INIS)

    Objective: To establish the immortalized cell lines of peripheral blood lymphocytes for old male residents in high background radiation area (HBRA) in Guangdong, China, in order to preserve the specific genomic resources of residents in HBRA for the further genetic and molecular biological study on HBRA. Methods: The peripheral blood samples of 20 old male residents in HBRA were collected after informed consent. The immortalized B lymphoblastoid cell lines, 2 fox each resident, were established with Epstein-Barr virus. After being frozen and recovered, the cell viability, the contamination of bacterium and mycoplasma were analyzed. The stabilization of cell lines was decided by comparing the karyotypes of the peripheral blood lymphocytes and the cell lines. Results: 40 cell lines for 20 residents in HBRA were successfully established.. The recovery rate of cell lines after being frozen was 100% . All the cell viablity after recovery was higher than 90%, and no contamination of bacteria and mycoplasma occurred. The karyotypes of the 20th generation cell lines were not change. Conclusion: The immortalized cell lines established in this study could provide biological resources for further study on genetics and molecular biology in HBRA. (authors)

  16. Shadows of the susceptible-infectious-susceptible immortality transition in small networks

    Science.gov (United States)

    Holme, Petter

    2015-07-01

    Much of the research on the behavior of the SIS model on networks has concerned the infinite size limit; in particular the phase transition between a state where outbreaks can reach a finite fraction of the population, and a state where only a finite number would be infected. For finite networks, there is also a dynamic transition—the immortality transition—when the per-contact transmission probability λ reaches 1. If λ <1 , the probability that an outbreak will survive by an observation time t tends to zero as t →∞ ; if λ =1 , this probability is 1. We show that treating λ =1 as a critical point predicts the λ dependence of the survival probability also for more moderate λ values. The exponent, however, depends on the underlying network. This fact could, by measuring how a vertex's deletion changes the exponent, be used to evaluate the role of a vertex in the outbreak. Our work also confirms an extremely clear separation between the early die-off (from the outbreak failing to take hold in the population) and the later extinctions (corresponding to rare stochastic events of several consecutive transmission events failing to occur).

  17. Inhibitory Effect of Nordy on HPV16 E6 Gene in Human Immortalized Endocervical Cells

    Institute of Scientific and Technical Information of China (English)

    CHEN Wei; ZHAO Yong; BIAN Xiu-wu

    2008-01-01

    Objective:To study the inhibitory effect of Nordy on HPV16 E6 gene in human immortalized endocervical cells(H8). Methods:The expressions of E6 and p53 proteins of H8 cells were detected by immunocytochemistry,and the expression of HPV16E6 mRNA of H8 cells was detected by RT-PCR. Results:According to immunocytochemistry,expressions of E6 and p53 proteins of H8 cells after treatment with 100 μmol/L Nordy for 72 h were weaker than control group obviously.After treatment with 50,100,200 μmol/L Nordy for 72 h.HPV16E6 mRNA expressions of H8 cells were lower than the control group significantly(P<0.05).Conclusion:Nordy could inhibit the expression of HPV16 E6 mRNA in H8 cells,influence transcription of E6 gene and result in decreased expressions of E6 and p53 proteins.

  18. Selling space colonization and immortality: A psychosocial, anthropological critique of the rush to colonize Mars

    Science.gov (United States)

    Slobodian, Rayna Elizabeth

    2015-08-01

    Extensive media coverage regarding the proposal to send four people to Mars by 2025 has exploded recently. Private enterprise has taken the reins to venture into space, which has typically only been reserved for government agencies. I argue, that with this new direction comes less regulation, raising questions regarding the ethics of sending people into outer space to colonize Mars within a decade. Marketers selling colonization to the public include perspectives such as biological drives, species survival, inclusiveness and utopian ideals. I challenge these narratives by suggesting that much of our desire to colonize space within the next decade is motivated by ego, money and romanticism. More specifically, I will examine the roles that fear and stories of immortality play within selling space and how those stories are marketed. I am passionate about space and hope that one day humanity will colonize other worlds, but the rush to settle is dangerous and careless. I assert that humanity should first gain more experience and knowledge before colonizing outer space, using this research to mitigate the risk to astronauts and proceed with careful consideration for the lives of potential astronauts.

  19. Characterization of cloned cells from an immortalized fetal pulmonary type II cell line

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, R.F.; Waide, J.J.; Lechner, J.F.

    1995-12-01

    A cultured cell line that maintained expression of pulmonary type II cell markers of differentiation would be advantageous to generate a large number of homogenous cells in which to study the biochemical functions of type II cells. Type II epithelial cells are the source of pulmonary surfactant and a cell of origin for pulmonary adenomas. Last year our laboratory reported the induction of expression of two phenotypic markers of pulmonary type II cells (alkaline phosphatase activity and surfactant lipid synthesis) in cultured fetal rat lung epithelial (FRLE) cells, a spontaneously immortalized cell line of fetal rat lung type II cell origin. Subsequently, the induction of the ability to synthesize surfactant lipid became difficult to repeat. We hypothesized that the cell line was heterogenuous and some cells were more like type II cells than others. The purpose of this study was to test this hypothesis and to obtain a cultured cell line with type II cell phenotypic markers by cloning several FRLE cells and characterizing them for phenotypic markers of type II cells (alkaline phosphatase activity and presence of surfactant lipids). Thirty cloned cell lines were analyzed for induced alkaline phosphatase activity (on x-axis) and for percent of phospholipids that were disaturated (i.e., surfactant).

  20. Mapping of imprinted quantitative trait loci using immortalized F2 populations.

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    Yongxian Wen

    Full Text Available Mapping of imprinted quantitative trait loci (iQTLs is helpful for understanding the effects of genomic imprinting on complex traits in animals and plants. At present, the experimental designs and corresponding statistical methods having been proposed for iQTL mapping are all based on temporary populations including F2 and BC1, which can be used only once and suffer some other shortcomings respectively. In this paper, we propose a framework for iQTL mapping, including methods of interval mapping (IM and composite interval mapping (CIM based on conventional low-density genetic maps and point mapping (PM and composite point mapping (CPM based on ultrahigh-density genetic maps, using an immortalized F2 (imF2 population generated by random crosses between recombinant inbred lines or doubled haploid lines. We demonstrate by simulations that imF2 populations are very desirable and the proposed statistical methods (especially CIM and CPM are very powerful for iQTL mapping, with which the imprinting effects as well as the additive and dominance effects of iQTLs can be unbiasedly estimated.

  1. Characterization of lipid metabolism in insulin-sensitive adipocytes differentiated from immortalized human mesenchymal stem cells

    International Nuclear Information System (INIS)

    There is a great demand for cell models to study human adipocyte function. Here we describe the adipogenic differentiation of a telomerase-immortalized human mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of terminally differentiated adipocytes even after prolonged withdrawal of the peroxisome proliferator activated receptor γ (PPARγ) agonist rosiglitazone. Differentiated hMSC-Tert developed the characteristic monolocular phenotype of mature adipocytes. The expression of adipocyte specific markers was highly increased during differentiation. Most importantly, the presence of the PPARγ agonist rosiglitazone was not required for the stable expression of lipoprotein lipase, adipocyte fatty acid binding protein and perilipin on mRNA and protein levels. Adiponectin expression was post-transcriptionally down-regulated in the absence of rosiglitazone. Insulin sensitivity as measured by insulin-induced phosphorylation of Akt and S6 ribosomal protein was also independent of rosiglitazone. In addition to commonly used adipogenic markers, we investigated further PPARγ-stimulated proteins with a role in lipid metabolism. We observed an increase of lipoprotein receptor (VLDLR, LRP1) and apolipoprotein E expression during differentiation. Despite this increased expression, the receptor-mediated endocytosis of lipoproteins was decreased in differentiated adipocytes, suggesting that these proteins may have an additional function in adipose tissue beyond lipoprotein uptake

  2. Immortalization of pig fibroblast cells by transposon-mediated ectopic expression of porcine telomerase reverse transcriptase.

    Science.gov (United States)

    He, Shan; Li, Yangyang; Chen, Yang; Zhu, Yue; Zhang, Xinyu; Xia, Xiaoli; Sun, Huaichang

    2016-08-01

    Pigs are the most economically important livestock, but pig cell lines useful for physiological studies and/or vaccine development are limited. Although several pig cell lines have been generated by oncogene transformation or human telomerase reverse transcriptase (TERT) immortalization, these cell lines contain viral sequences and/or antibiotic resistance genes. In this study, we established a new method for generating pig cell lines using the Sleeping Beauty (SB) transposon-mediated ectopic expression of porcine telomerase reverse transcriptase (pTERT). The performance of the new method was confirmed by generating a pig fibroblast cell (PFC) line. After transfection of primary PFCs with the SB transposon system, one cell clone containing the pTERT expression cassette was selected by dilution cloning and passed for different generations. After passage for more than 40 generations, the cell line retained stable expression of ectopic pTERT and continuous growth potential. Further characterization showed that the cell line kept the fibroblast morphology, growth curve, population doubling time, cloning efficiency, marker gene expression pattern, cell cycle distribution and anchorage-dependent growth property of the primary cells. These data suggest that the new method established is useful for generating pig cell lines without viral sequence and antibiotic resistant gene. PMID:26341227

  3. Generation and characterization of the first immortalized alpaca cell line suitable for diagnostic and immunization studies.

    Directory of Open Access Journals (Sweden)

    Valentina Franceschi

    Full Text Available Raising of alpacas as exotic livestock for wool and meat production and as companion animals is growing in importance in the United States, Europe and Australia. Furthermore the alpaca, as well as the rest of the camelids, possesses the peculiarity of producing single-chain antibodies from which nanobodies can be generated. Nanobodies, due to their structural simplicity and reduced size, are very versatile in terms of manipulation and bio-therapeutic exploitation. In fact the biotech companies involved in nanobody production and application continue to grow in number and size. Hence, the development of reagents and tools to assist in the further growth of this new scientific and entrepreneurial reality is becoming a necessity. These are needed mainly to address alpaca disease diagnosis and prophylaxis, and to develop alpaca immunization strategies for nanobody generation. For instance an immortalized alpaca cell line would be extremely valuable. In the present work the first stabilized alpaca cell line from alpaca skin stromal cells (ASSCs was generated and characterized. This cell line was shown to be suitable for replication of viruses bovine herpesvirus-1, bovine viral diarrhea virus and caprine herpesvirus-1 and the endocellular parasite Neospora caninum. Moreover ASSCs were easy to transfect and transduce by several methods. These two latter characteristics are extremely useful when recombinant antigens need to be produced in a host homologous system. This work could be considered as a starting point for the expansion of the biotechnologies linked to alpaca farming and industry.

  4. Cooperation of c-raf-1 and c-myc protooncogenes in the neoplastic transformation of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Overexpression of c-raf-1 and the myc family of protooncogenes is primarily associated with small cell carcinoma, which accounts for ∼ 25% of human lung cancer. To determine the functional significance of the c-raf-1 and/or c-myc gene expression in lung carcinogenesis and to delineate the relationship between protooncogene expression and tumor phenotype, the authors introduced both protooncogenes, alone or in combination, into human bronchial epithelial cells. Two retroviral recombinants, pZip-raf and pZip-myc, containing the complete coding sequences of the human c-raf-1 and murine c-myc genes, respectively, were constructed and transfected into simian virus 40 large tumor antigen-immortalized bronchial epithelial cells (BEAS-2B); this was followed by selection for G418 resistance. Cell lines established from tumors (designated RMT) revealed the presence of the cotransfected c-raf-1 and c-myc sequences and expressed morphological, chromosomal, and isoenzyme markers, which identified BEAS-2B cells as the progenitor line of the tumors. The data demonstrate that the concomitant expression of the c-raf and c-myc protooncogenes causes neoplastic transformation of human bronchial epithelial cells resulting in large cell carcinomas with certain neuroendocrine markers. The presented model system should be useful in studies of molecular events involved in multistage lung carcinogenesis

  5. Differential localization of cytoplasmic myosin II isoforms A and B in avian interphase and dividing embryonic and immortalized cardiomyocytes and other cell types in vitro

    Science.gov (United States)

    Conrad, A. H.; Jaffredo, T.; Conrad, G. W.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    Two principal isoforms of cytoplasmic myosin II, A and B (CMIIA and CMIIB), are present in different proportions in different tissues. Isoform-specific monoclonal and polyclonal antibodies to avian CMIIA and CMIIB reveal the cellular distributions of these isoforms in interphase and dividing embryonic avian cardiac, intestinal epithelial, spleen, and dorsal root ganglia cells in primary cell culture. Embryonic cardiomyocytes react with antibodies to CMIIB but not to CMIIA, localize CMIIB in stress-fiber-like-structures during interphase, and markedly concentrate CMIIB in networks in the cleavage furrow during cytokinesis. In contrast, cardiac fibroblasts localize both CMIIA and CMIIB in stress fibers and networks during interphase, and demonstrate slight and independently regulated concentration of CMIIA and CMIIB in networks in their cleavage furrows. V-myc-immortalized cardiomyocytes, an established cell line, have regained the ability to express CMIIA, as well as CMIIB, and localize both CMIIA and CMIIB in stress fibers and networks in interphase cells and in cleavage furrows in dividing cells. Conversely, some intestinal epithelial, spleen, and dorsal root ganglia interphase cells express only CMIIA, organized primarily in networks. Of these, intestinal epithelial cells express both CMIIA and CMIIB when they divide, whereas some dividing cells from both spleen and dorsal root ganglia express only CMIIA and concentrate it in their cleavage furrows. These results suggest that within a given tissue, different cell types express different isoforms of CMII, and that cells expressing either CMIIA or CMIIB alone, or simultaneously, can form a cleavage furrow and divide.

  6. Differential response of primary and immortalized CD4+ T cells to Neisseria gonorrhoeae-induced cytokines determines the effect on HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Wendy N Dobson-Belaire

    Full Text Available To compare the effect of gonococcal co-infection on immortalized versus primary CD4(+ T cells the Jurkat cell line or freshly isolated human CD4(+ T cells were infected with the HIV-1 X4 strain NL4-3. These cells were exposed to whole gonococci, supernatants from gonococcal-infected PBMCs, or N. gonorrhoeae-induced cytokines at varying levels. Supernatants from gonococcal-infected PBMCs stimulated HIV-1 replication in Jurkat cells while effectively inhibiting HIV-1 replication in primary CD4(+ T cells. ELISA-based analyses revealed that the gonococcal-induced supernatants contained high levels of proinflammatory cytokines that promote HIV-1 replication, as well as the HIV-inhibitory IFNα. While all the T cells responded to the HIV-stimulatory cytokines, albeit to differing degrees, the Jurkat cells were refractory to IFNα. Combined, these results indicate that N. gonorrhoeae elicits immune-modulating cytokines that both activate and inhibit HIV-production; the outcome of co-infection depending upon the balance between these opposing signals.

  7. 1,25 dihydroxyvitamin D-mediated orchestration of anticancer, transcript-level effects in the immortalized, non-transformed prostate epithelial cell line, RWPE1

    Directory of Open Access Journals (Sweden)

    Clinton Steve K

    2010-01-01

    Full Text Available Abstract Background Prostate cancer is the second leading cause of cancer mortality among US men. Epidemiological evidence suggests that high vitamin D status protects men from prostate cancer and the active form of vitamin D, 1α,25 dihydroxyvitamin D3 (1,25(OH2D has anti-cancer effects in cultured prostate cells. Still, the molecular mechanisms and the gene targets for vitamin D-mediated prostate cancer prevention are unknown. Results We examined the effect of 1,25(OH2D (+/- 100 nM, 6, 24, 48 h on the transcript profile of proliferating RWPE1 cells, an immortalized, non-tumorigenic prostate epithelial cell line that is growth arrested by 1,25(OH2D (Affymetrix U133 Plus 2.0, n = 4/treatment per time and dose. Our analysis revealed many transcript level changes at a 5% false detection rate: 6 h, 1571 (61% up, 24 h, 1816 (60% up, 48 h, 3566 (38% up. 288 transcripts were regulated similarly at all time points (182 up, 80 down and many of the promoters for these transcripts contained putative vitamin D response elements. Functional analysis by pathway or Gene Set Analysis revealed early suppression of WNT, Notch, NF-kB, and IGF1 signaling. Transcripts related to inflammation were suppressed at 6 h (e.g. IL-1 pathway and suppression of proinflammatory pathways continued at later time points (e.g. IL-17 and IL-6 pathways. There was also evidence for induction of anti-angiogenic pathways and induction of transcripts for protection from oxidative stress or maintenance of cell redox homeostasis at 6 h. Conclusions Our data reveal of large number of potential new, direct vitamin D target genes relevant to prostate cancer prevention. In addition, our data suggests that rather than having a single strong regulatory effect, vitamin D orchestrates a pattern of changes within prostate epithelial cells that limit or slow carcinogenesis.

  8. Ethyl pyruvate regulates the levels of leptin, lactin acid-pyruvic, ALT and UA in mice sepsis model

    International Nuclear Information System (INIS)

    To explore the effect of ethyl pyruvate (EP) on the serum levels of leptin, lactin acid to pyruvic acid ratio, ALT and UA in sepsis mice. The mice sepsis model of cecum ligation and perforation was established. The 90 male mice were divided randomly into sham-operation ( Sham), injury (RLS) and EP(REPS)-intervened groups, the latter two groups were further divided into 15 min, 1 h, 3 h and 6 h subgroups, each of them had 10 mice. The serum lactin acid to pyruvic acid ratio, ALT and UA were detected by autonomous biochemical analyzer, and the serum leptin were detected by RIA. The results showed that the serum leptin level in REPS group was significantly higher than that of in RLS group at the later phase (P<0.05). The ratio of lactin acid to pyruvic acid in RLS and REPS groups were significantly higher that of in sham group, but there is no significant different between REPS group and RLS group at same time points. The serum levels of ALT in RLS and REPS groups were significantly higher than that of in Sham group, and the serum level of ALT in REPS group at later time points was significantly higher than that of RLS group. Compared with Sham group, the serum UA in RLS group was increased significantly at first time points (P<0.05) and then decreased at later time points; the serum UA in REPS group was significantly lower than that of RLS group (P<0.05). The results indicated that EP may protect renal function, worsen hepatic injury at the early phase and up-regulate the serum leptin level. (authors)

  9. Liver Enzymes: Interaction Analysis of Smoking with Alcohol Consumption or BMI, Comparing AST and ALT to γ-GT

    OpenAIRE

    Breitling, Lutz P.; Arndt, Volker; Drath, Christoph; Brenner, Hermann

    2011-01-01

    Background A detrimental interaction between smoking and alcohol consumption with respect serum γ-glutamyltransferase (γ-GT) has recently been described. The underlying mechanisms remain unknown. The present work aimed to provide further insights by examining similar interactions pertaining to aspartate and alanine transaminase (AST, ALT), routine liver markers less prone to enzyme induction. Methodology/Principal Findings The present cross-sectional analysis was based on records from routine...

  10. Isolation and characterization of a spontaneously immortalized bovine retinal pigmented epithelial cell line

    Directory of Open Access Journals (Sweden)

    Griffiths T Daniel

    2009-05-01

    Full Text Available Abstract Background The Retinal Pigmented Epithelium (RPE is juxtaposed with the photoreceptor outer segments of the eye. The proximity of the photoreceptor cells is a prerequisite for their survival, as they depend on the RPE to remove the outer segments and are also influenced by RPE cell paracrine factors. RPE cell death can cause a progressive loss of photoreceptor function, which can diminish vision and, over time, blindness ensues. Degeneration of the retina has been shown to induce a variety of retinopathies, such as Stargardt's disease, Cone-Rod Dystrophy (CRD, Retinitis Pigmentosa (RP, Fundus Flavimaculatus (FFM, Best's disease and Age-related Macular Degeneration (AMD. We have cultured primary bovine RPE cells to gain a further understanding of the mechanisms of RPE cell death. One of the cultures, named tRPE, surpassed senescence and was further characterized to determine its viability as a model for retinal diseases. Results The tRPE cell line has been passaged up to 150 population doublings and was shown to be morphologically similar to primary cells. They have been characterized to be of RPE origin by reverse transcriptase PCR and immunocytochemistry using the RPE-specific genes RPE65 and CRALBP and RPE-specific proteins RPE65 and Bestrophin. The tRPE cells are also immunoreactive to vimentin, cytokeratin and zonula occludens-1 antibodies. Chromosome analysis indicates a normal diploid number. The tRPE cells do not grow in suspension or in soft agar. After 3H thymidine incorporation, the cells do not appear to divide appreciably after confluency. Conclusion The tRPE cells are immortal, but still exhibit contact inhibition, serum dependence, monolayer growth and secrete an extra-cellular matrix. They retain the in-vivo morphology, gene expression and cell polarity. Additionally, the cells endocytose exogenous melanin, A2E and purified lipofuscin granules. This cell line may be a useful in-vitro research model for retinal

  11. Expression of keratins in normal, immortalized and malignant oral epithelia in organotypic culture.

    Science.gov (United States)

    Hansson, A; Bloor, B K; Haig, Y; Morgan, P R; Ekstrand, J; Grafström, R C

    2001-07-01

    Keratins have been extensively studied in tissues and cultured keratinocytes but limited information is available on epithelia reconstructed in vitro. The aim of this study was to examine keratin expression in organotypic epithelia with normal (NOK), immortalized (SVpgC2a) and malignant (SqCC/Y1) human buccal cells. Organotypic epithelia were derived from 10 days of culture at the air-liquid interface of collagen gels containing human oral fibroblasts using a standardized serum-free medium. Sections were stained immunohistochemically with selected mono-specific antibodies to a range of keratins. Organotypic epithelia showed sharp differences in keratin expression and distribution. K4/K13, K1/K10, K6/K16 were variably expressed in NOK and SqCC/Y1 but were not detected in SVpgC2a. K5 was expressed in all organotypic epithelia but K14 was absent in SVpgC2a. K7 and K8 showed variable expression while K18 was expressed uniformly in all epithelia. K19 was expressed consistently in NOK and K20 was distributed heterogeneously in SVpgC2a. Overall, organotypic cultures of normal keratinocytes express many of the same keratins as buccal mucosa. Further, the loss of keratins in SVpgC2a and their retention in SqCC/Y1 have several features in common with the respective keratin profile of oral epithelial dysplasia and well-differentiated oral squamous cell carcinoma. Although qualitative and quantitative differences exist compared to keratin expression in vivo, these cell lines in organotypic culture may serve in studies of the multi-step progression of oral cancer.

  12. Establishment and characterization of immortalized Gli-null mouse embryonic fibroblast cell lines

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    Gipp Jerry J

    2008-09-01

    Full Text Available Abstract Background Hedgehog (Hh signaling is a conserved morphogenetic pathway which plays critical roles in embryonic development, with emerging evidence also supporting a role in healing and repair processes and tumorigenesis. The Gli family of transcription factors (Gli1, 2 and 3 mediate the Hedgehog morphogenetic signal by regulating the expression of downstream target genes. We previously characterized the individual and cooperative roles of the Gli proteins in Hh target gene regulation using a battery of primary embryonic fibroblasts from Gli null mice. Results Here, we describe the establishment of spontaneously immortalized mouse embryonic fibroblast (iMEF cell lines lacking single and multiple Gli genes. These non-clonal cell lines recapitulate the unique ligand mediated transcriptional response of primary MEFs. While loss of Gli1 had no effect on target gene induction, Gli2 null cells demonstrated reduced target gene induction while Gli3 null cells exhibited elevated basal and ligand-induced expression. Target gene response in Gli1-/-2-/- iMEFs was severely reduced while Gli2-/-3-/- iMEFs were incapable of ligand-induced transcriptional response. However, we found that both Gli1-/-2-/- and Gli2-/-3-/- iMEFs exhibited robust leukotriene synthesis-dependent migration responses to Hh ligand, demonstrating that this response is not transcriptionally-dependent. Conclusion This study provides fundamental characterizations of the transcriptional and non-transcriptional Hh responsiveness of a battery of Gli-null iMEFs. Moving forward, these cell lines should prove a valuable tool set to study the unique functional regulation of the Gli proteins in a Hh-responsive cell-type.

  13. Arsenic compromises conducting airway epithelial barrier properties in primary mouse and immortalized human cell cultures.

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    Cara L Sherwood

    Full Text Available Arsenic is a lung toxicant that can lead to respiratory illness through inhalation and ingestion, although the most common exposure is through contaminated drinking water. Lung effects reported from arsenic exposure include lung cancer and obstructive lung disease, as well as reductions in lung function and immune response. As part of their role in innate immune function, airway epithelial cells provide a barrier that protects underlying tissue from inhaled particulates, pathogens, and toxicants frequently found in inspired air. We evaluated the effects of a five-day exposure to environmentally relevant levels of arsenic {<4μM [~300 μg/L (ppb] as NaAsO2} on airway epithelial barrier function and structure. In a primary mouse tracheal epithelial (MTE cell model we found that both micromolar (3.9 μM and submicromolar (0.8 μM arsenic concentrations reduced transepithelial resistance, a measure of barrier function. Immunofluorescent staining of arsenic-treated MTE cells showed altered patterns of localization of the transmembrane tight junction proteins claudin (Cl Cl-1, Cl-4, Cl-7 and occludin at cell-cell contacts when compared with untreated controls. To better quantify arsenic-induced changes in tight junction transmembrane proteins we conducted arsenic exposure experiments with an immortalized human bronchial epithelial cell line (16HBE14o-. We found that arsenic exposure significantly increased the protein expression of Cl-4 and occludin as well as the mRNA levels of Cl-4 and Cl-7 in these cells. Additionally, arsenic exposure resulted in altered phosphorylation of occludin. In summary, exposure to environmentally relevant levels of arsenic can alter both the function and structure of airway epithelial barrier constituents. These changes likely contribute to the observed arsenic-induced loss in basic innate immune defense and increased infection in the airway.

  14. Accumulation and altered localization of telomere-associated protein TRF2 in immortally transformed and tumor-derived human breast cells

    Energy Technology Data Exchange (ETDEWEB)

    Nijjar, Tarlochan; Bassett, Ekaterina; Garbe, James; Takenaka, Yasuhiro; Stampfer, Martha R.; Gilley, David; Yaswen, Paul

    2004-12-23

    We have used cultured human mammary epithelial cells (HMEC) and breast tumor-derived lines to gain information on defects that occur during breast cancer progression. HMEC immortalized by a variety of agents (the chemical carcinogen benzo(a)pyrene, oncogenes c-myc and ZNF217, and/or dominant negative p53 genetic suppressor element GSE22) displayed marked up regulation (10-15 fold) of the telomere binding protein, TRF2. Up-regulation of TRF2 protein was apparently due to differences in post-transcriptional regulation, as mRNA levels remained comparable in finite life span and immortal HMEC. TRF2 protein was not up-regulated by the oncogenic agents alone in the absence of immortalization, nor by expression of exogenously introduced hTERT genes. We found TRF2 levels to be at least 2-fold higher than in control cells in 11/15 breast tumor cell lines, suggesting that elevated TRF2 levels are a frequent occurrence during the transformation of breast tumor cells in vivo. The dispersed distribution of TRF2 throughout the nuclei in some immortalized and tumor-derived cells indicated that not all the TRF2 was associated with telomeres in these cells. The process responsible for accumulation of TRF2 in immortalized HMEC and breast tumor-derived cell lines may promote tumorigenesis by contributing to the cells ability to maintain an indefinite life span.

  15. Production and Functional Characterization of Murine Osteoclasts Differentiated from ER-Hoxb8-Immortalized Myeloid Progenitor Cells.

    Science.gov (United States)

    Zach, Frank; Mueller, Alexandra; Gessner, André

    2015-01-01

    In vitro differentiation into functional osteoclasts is routinely achieved by incubation of embryonic stem cells, induced pluripotent stem cells, or primary as well as cryopreserved spleen and bone marrow-derived cells with soluble receptor activator of nuclear factor kappa-B ligand and macrophage colony-stimulating factor. Additionally, osteoclasts can be derived from co-cultures with osteoblasts or by direct administration of soluble receptor activator of nuclear factor kappa-B ligand to RAW 264.7 macrophage lineage cells. However, despite their benefits for osteoclast-associated research, these different methods have several drawbacks with respect to differentiation yields, time and animal consumption, storage life of progenitor cells or the limited potential for genetic manipulation of osteoclast precursors. In the present study, we therefore established a novel protocol for the differentiation of osteoclasts from murine ER-Hoxb8-immortalized myeloid stem cells. We isolated and immortalized bone marrow cells from wild type and genetically manipulated mouse lines, optimized protocols for osteoclast differentiation and compared these cells to osteoclasts derived from conventional sources. In vitro generated ER-Hoxb8 osteoclasts displayed typical osteoclast characteristics such as multi-nucleation, tartrate-resistant acid phosphatase staining of supernatants and cells, F-actin ring formation and bone resorption activity. Furthermore, the osteoclast differentiation time course was traced on a gene expression level. Increased expression of osteoclast-specific genes and decreased expression of stem cell marker genes during differentiation of osteoclasts from ER-Hoxb8-immortalized myeloid progenitor cells were detected by gene array and confirmed by semi-quantitative and quantitative RT-PCR approaches. In summary, we established a novel method for the quantitative production of murine bona fide osteoclasts from ER-Hoxb8 stem cells generated from wild type or

  16. Production and Functional Characterization of Murine Osteoclasts Differentiated from ER-Hoxb8-Immortalized Myeloid Progenitor Cells.

    Directory of Open Access Journals (Sweden)

    Frank Zach

    Full Text Available In vitro differentiation into functional osteoclasts is routinely achieved by incubation of embryonic stem cells, induced pluripotent stem cells, or primary as well as cryopreserved spleen and bone marrow-derived cells with soluble receptor activator of nuclear factor kappa-B ligand and macrophage colony-stimulating factor. Additionally, osteoclasts can be derived from co-cultures with osteoblasts or by direct administration of soluble receptor activator of nuclear factor kappa-B ligand to RAW 264.7 macrophage lineage cells. However, despite their benefits for osteoclast-associated research, these different methods have several drawbacks with respect to differentiation yields, time and animal consumption, storage life of progenitor cells or the limited potential for genetic manipulation of osteoclast precursors. In the present study, we therefore established a novel protocol for the differentiation of osteoclasts from murine ER-Hoxb8-immortalized myeloid stem cells. We isolated and immortalized bone marrow cells from wild type and genetically manipulated mouse lines, optimized protocols for osteoclast differentiation and compared these cells to osteoclasts derived from conventional sources. In vitro generated ER-Hoxb8 osteoclasts displayed typical osteoclast characteristics such as multi-nucleation, tartrate-resistant acid phosphatase staining of supernatants and cells, F-actin ring formation and bone resorption activity. Furthermore, the osteoclast differentiation time course was traced on a gene expression level. Increased expression of osteoclast-specific genes and decreased expression of stem cell marker genes during differentiation of osteoclasts from ER-Hoxb8-immortalized myeloid progenitor cells were detected by gene array and confirmed by semi-quantitative and quantitative RT-PCR approaches. In summary, we established a novel method for the quantitative production of murine bona fide osteoclasts from ER-Hoxb8 stem cells generated from

  17. Multi-signal components combining acquisition method based on padding zero for TD-AltBOC%补0的 TD-AltBOC 多信号分量联合捕获方法

    Institute of Scientific and Technical Information of China (English)

    杨建雷; 金天; 黄智刚; 秦红磊

    2014-01-01

    针对TD-AltBOC导频路和数据路码片时分复用,四信号分量码相位相同的特点,提出了补0的TD-AltBOC多信号分量联合捕获方法。该方法通过将本地复制的TD-AltBOC信号奇数和偶数码片伪随机码分别补0消除相邻码片数据跳变造成的相关峰损失,将4个信号分量的相关值进行多种相干组合,选取最优的相干组合相关值作为最终的统计判决量,解决了传统的单信号分量捕获方法损失信号能量的问题。从理论上分析了TD-AltBOC信号码片时分复用对传统FFT捕获方法性能的影响,推导了所提出方法的虚警概率和检测概率表达式。理论和仿真结果表明:所提出的方法比传统FFT 方法和GPS L2C CM码单信号分量捕获方法提高捕获灵敏度3~6 dB,降低平均捕获时间5%~35%,当载噪比为38 dB-Hz,虚警概率为0.1%时,检测概率可达80%。%In TD-AltBOC structure, the data and pilot chips are time-divisional and the four signal components have the same code phase.According to these characteristics, a multi-signal components combining acquisition method based on padding zero was proposed.In this method, the local replicated odd and even chip pseudorandom noise (PN) codes were padded with zero, respectively.This allows for the elimination of the correlation peak loss caused by bit transitions of ad-jacent chips.The correlation values of the four signal components were coherently combined and the optimal correlation value was selected as the final decision variable.This method can solve the signal energy loss problem in the traditional single signal component acquisition.The influence of the time-division multiplexing of TD-Alt BOC signal chips using a traditional FFT acquisition method was analyzed in theory, and the false probability and detection probability expression were deduced.The theoretical and simulated results showed that the proposed method can provide 3~6 dB acquisition

  18. Immortalization of epithelial-like cells from human liver tissue with SV40 T-antigen gene.

    Science.gov (United States)

    Miyazaki, M; Mihara, K; Bai, L; Kano, Y; Tsuboi, S; Endo, A; Seshimo, K; Yoshioka, T; Namba, M

    1993-05-01

    The cells derived from the human embryo liver tissue were transfected with a plasmid pSV3neo containing both the large and small T-antigen gene of the early region of simian virus 40 (SV40), and two cell strains, OUMS-21 and -22, were obtained. OUMS-22 cells, to date, have reached over 100 population doublings through a culture crisis and are considered to have become an immortal cell line. However, OUMS-21 cells failed to become an immortal cell line. Both OUMS-21 and -22 cells were SV40 T-antigen-positive, epithelial-like, and immunoreactive against an anti-keratin 18 monoclonal antibody but against neither an anti-vimentin nor an anti-von Willebrandt factor VIII monoclonal antibody. The staining pattern of cytokeratin in these cells was similar to that in the differentiated human hepatoblastoma and hepatocellular carcinoma cell lines but not to that in the human cholangiocellular carcinoma cell lines. OUMS-21 and -22 cells expressed neither alpha-fetoprotein nor albumin mRNAs. These cells showed no tyrosine aminotransferase activity. However, both OUMS-21 and -22 cells were sensitive to cytotoxicity of aflatoxin B1, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, and benzo[a]pyrene, whereas human embryo lung fibroblasts were insensitive to the cytotoxicity of these carcinogens. These findings suggest that OUMS-21 and -22 cells may arise from undifferentiated liver stem cells or from hepatocytes that lost their ability to express the liver-specific functions prior to immortalization. Both OUMS-21 and -22 cells expressed glutathione S-transferase pi (GST-pi) mRNA. The expression of GST-pi mRNA highly increased in OUMS-22 cells with their immortalization. Karyotypic analysis showed that numerical and structural aberrations of the chromosomes were profound, but neither specific events nor marker chromosomes were found in OUMS-21 and -22 cells. Both OUMS-21 and -22 cells could grow in soft agar, but they were not tumorigenic when transplanted into nude mice. PMID

  19. Artichoke compound cynarin differentially affects the survival, growth and stress response of normal, immortalized and cancerous human cells

    DEFF Research Database (Denmark)

    Gezer, Ceren; Yücecan, Sevinç; Rattan, Suresh Inder Singh

    2015-01-01

    Cynarin (CYN) is the main derivative of caffeoylquinic acid, found in leaves and heads of artichoke. Potential health-beneficial effects of CYN include as being choloretic-cholesterol lowering, hepatoprotective, anti-atherosclerotic, and antioxidative. We have tested the effects of various doses...... of CYN on the proliferative potential, survival, morphology, and stress response (SR) markers haemoxygenase-1 (HO-1) and heat shock protein-70 (HSP70) in normal human skin fibroblasts (FSF-1), telomerase-immortalized mesenchymal stem cells (hTERT-MSC) and cervical cancer cells, HeLa. Effects of CYN...

  20. Disseny d'un mètode de valoració d'itineraris d'educació ambiental i aplicació a l'àmbit Parc Natural de l'Alt Pirineu - Alt Urgell

    OpenAIRE

    EDUCCAMB (Grup de recerca); Nualart i Nieto, Anna; Arroyo i Moras, Fco. Javier; Pujantell i Albós, Josep Antoni; Duch Cortinas, Jordi; Masqué Barri, Pere; Rieradevall, Joan; Ramon Riba, Antoni

    2007-01-01

    El Parc Natural de l'Alt Pirineu (PNAP) està creant una xarxa d'itineraris d'educació ambiental amb l'objectiu de divulgar els valors del parc i conscienciar els seus visitants sobre la importància de conservar el medi ambient. El desenvolupament de mètodes de valoració de l'aptitud de potencials itineraris d'educació ambiental pot servir per crear eines de gestió molt útils a l'hora d'ampliar aquesta xarxa de senders. Per aquest motiu, un grup anterior de la llicenciatura de Ciències Ambient...

  1. Beierlorzer, Henry , Boll, Joachim , Ganser, Karl (Hg.), SiedlungsKultur : neue und alte Gartenstädte im Ruhrgebiet / [rezensiert von] Hans-Werner Wehling

    OpenAIRE

    Wehling, Hans-Werner

    2008-01-01

    Rezensiertes Werk: Siedlungs-Kultur : neue und alte Gartenstädte im Ruhrgebiet / IBA Emscher-Park. Hrsg. von Henry Beierlorzer ... - Braunschweig ; Wiesbaden : Vieweg, 1999. - 166 S. : zahlr. Ill., graph. Darst. ISBN 3-528-02425-9

  2. GIPL1.3 simulated maximum active layer thickness (ALT) in meters averaged for particular decade for the entire Alaskan permafrost domain. NAD83, Alaska Albers projection

    Data.gov (United States)

    Arctic Landscape Conservation Cooperative — This raster, created in 2010, is output from the Geophysical Institute Permafrost Lab (GIPL) model and represents simulated active layer thickness (ALT) in meters...

  3. 庄子“真人”考辨%A Study of the "Immortal Man" Put forward by Zhuang Zi

    Institute of Scientific and Technical Information of China (English)

    张清河

    2011-01-01

    庄子《大宗师》中出现了四则有关“真人”的论述。通过《庄子》全书的比读,可知真人是庄子自身理想人格的画像,等同于“至人”。真人一旦上升到“道”的层面,又等同于“神人”。真人思想的矛盾性源自《庄子》材料来源的复杂性。作为天道哲学的真人,其思想源自《道德经》、《山海经》等典籍;作为生命哲学的真人,源自《黄帝内经》、《周易》等。由后者形成一种“葆真”的生命哲学观,产生了积极的深远影响。%The "immortal man" appeared in four parts of the Dazongshi by Zhuang Zi: After reading the chapters of Zhuang Zi, we can look on the "immortal man" as Zhuang Zi's own portrait of the immortal personality, the same as the "perfect man." Once the immortal man combines with the way of heaven, the "immortal man" is equivalent to the "deity". The contradiction within the immortal man thoughts results from the complexity of the source material in Zhuang Zi. Based on the philosophy of Heaven, the thoughts originated from Dao De Jing by Lao Zi, Shan Hai Jing and other books; based on the "immortal" philosophy of life, from The Yellow Emperor's Classic of Internal Medicine, The Book of Changes and so on.

  4. A Styrene-alt-Maleic Acid Copolymer Is an Effective Inhibitor of R5 and X4 Human Immunodeficiency Virus Type 1 Infection

    Directory of Open Access Journals (Sweden)

    Vanessa Pirrone

    2010-01-01

    Full Text Available An alternating copolymer of styrene and maleic acid (alt-PSMA differs from other polyanionic antiviral agents in that the negative charges of alt-PSMA are provided by carboxylic acid groups instead of sulfate or sulfonate moieties. We hypothesized that alt-PSMA would have activity against human immunodeficiency virus type 1 (HIV-1 comparable to other polyanions, such as the related compound, poly(sodium 4-styrene sulfonate (PSS. In assays using cell lines and primary immune cells, alt-PSMA was characterized by low cytotoxicity and effective inhibition of infection by HIV-1 BaL and IIIB as well as clinical isolates of subtypes A, B, and C. In mechanism of action assays, in which each compound was added to cells and subsequently removed prior to HIV-1 infection (“washout” assay, alt-PSMA caused no enhancement of infection, while PSS washout increased infection 70% above control levels. These studies demonstrate that alt-PSMA is an effective HIV-1 inhibitor with properties that warrant further investigation.

  5. Politiken, Alt om Ikast Brande (web), Lemvig Folkeblad (Web), Politiken (web), Dabladet Ringkjøbing Skjern (web)

    DEFF Research Database (Denmark)

    Lauritsen, Jens

    2014-01-01

    Politiken 01.01.2014 14:16 Danskerne skød nytåret ind med et brag, men for enkeltes vedkommende gik det galt, da nytårskrudtet blev tændt. Skadestuerne har behandlet 73 personer for fyrværkeriskader mellem klokken 18 i aftes og klokken 06 i morges. Det viser en optælling, som Politiken har...... foretaget på baggrund af tal fra Ulykkes Analyse Gruppen på Odense Universitetshospital. Artiklen er også bragt i: Alt om Ikast Brande (web), Lemvig Folkeblad (web), Politiken (web), Dagbladet Ringkjøbing Skjern (web)....

  6. SYNTHESIS AND CHARACTERIZATION OF A NEW COMBLIKE POLYMER BASED ON POLY (VINYL METHYL ETHER-ALT-MALEIC ANHYDRIDE) BACKBONE

    Institute of Scientific and Technical Information of China (English)

    DING Liming; LIN Yunqing; ZHOU Zinan; NI Jianlong; CHEN Donglin

    1995-01-01

    A new comblike polymer host for polymer electrolyte was synthesized by reacting monomethyl ether of poly(ethylene glycol) with poly(vinyl methyl ether-alt-maleic anhydride) and endcapping the residual carboxylic acid with methanol. Butanone was selected as a solvent for the esterification in order to obtain a completely soluble product. The synthesis process was traced through by IR. Compared with the model compounds, the presumed structure of this comblike polymer has been proved to be valid by 13C NMR. The comb polymer is a white rubbery solid. It can be dissolved in butanone and THF, and manifests good film forming ability.

  7. Mechanistic Aspects of Monomer,Polymer Formation,and Synthesis of PQ-Alt-Dialkyl-fluorene Conjugated Copolymer

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Suzuki coupling reaction is widely used in the construction of conjugated polymers; however, there is still no report describing the mechanism and coupling of 9,10-phenanthrenequinone(PQ) building blocks via Suzuki reaction because PQ is sensitive to bases and light. Herein is reported the efficient Suzuki coupling of PQ with 9,10-dialkylfluorene with Na2CO3 as basic species and high molecular weight PQ-Alt-Dialkyl-Fluorene conjugated copolymer obtained in an yield of 42%. Based on the characterization data and well-accepted literature, we proposed a step-by-step mechanistic explanation for the formation of the PQ containing alternating conjugated copolymer.

  8. Effects of Ashwagandha (Withania somnifera Root Extract On Some Serum Liver Marker Enzymes (AST, ALT In Gentamicin Intoxicated Rats

    Directory of Open Access Journals (Sweden)

    Nayma Sultana

    2012-06-01

    Full Text Available Background: Liver is an essential metabolic organ. It can be damaged due to prolonged use and higher doses of drugs, exposure to some chemicals, toxins, or infectious agents. Herbal plants as ashwagandha (Withania somnifera may have free radical scavenging activity thereby can be used for the prevention and treatment of liver damage.Objective: To observe the effect of ashwagandha (Withania somnifera root extract on gentamicin induced changes of some liver marker enzymes e,g serum aspartate amino transferase (AST and alanine amino transferase (ALT in Wistar albino rats.Methods: This experimental study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC, Dhaka from 1st July 2010 to 30th June 2011. A total number of 35 Wistar albino rats, aged 90 to 120 days, weighing between 150 to 200 grams were selected for the study. After acclimatization for 14 days, they were divided into control group (Group A and experimental group (Group B. Control group was again subdivided into group A1 (baseline control, consisted of 10 rats and group A2 (gentamicin treated control group, consisted of 10 rats. Again, experimental group (Group B-ashwagandha pretreated and gentamicin treated group consisted of 15 rats. All groups of animals received basal diet for 22 consecutive days. In addition to this, group A2 also received gentamicin subcutaneously (100mg /kg body weight/day for the last eight (15th to 22nd day consecutive days. Again, group B received ashwagandha root extract (500mg/kg body weight/day, orally for 22 consecutive days and gentamicin subcutaneously (100mg/kg body weight /day for last eight (15th to 22nd day days. All the animals were sacrificed on 23rd day. Then blood and liver samples were collected. For assessment of liver function, serum AST, ALT and bilirubin levels were estimated. All these tests were done by standard Laboratory technique. The statistical analysis was done by one way ANOVA and Bonferroni test as

  9. Caenorhabditis elegans RSD-2 and RSD-6 promote germ cell immortality by maintaining small interfering RNA populations.

    Science.gov (United States)

    Sakaguchi, Aisa; Sarkies, Peter; Simon, Matt; Doebley, Anna-Lisa; Goldstein, Leonard D; Hedges, Ashley; Ikegami, Kohta; Alvares, Stacy M; Yang, Liwei; LaRocque, Jeannine R; Hall, Julie; Miska, Eric A; Ahmed, Shawn

    2014-10-14

    Germ cells are maintained in a pristine non-aging state as they proliferate over generations. Here, we show that a novel function of the Caenorhabditis elegans RNA interference proteins RNAi spreading defective (RSD)-2 and RSD-6 is to promote germ cell immortality at high temperature. rsd mutants cultured at high temperatures became progressively sterile and displayed loss of small interfering RNAs (siRNAs) that target spermatogenesis genes, simple repeats, and transposons. Desilencing of spermatogenesis genes occurred in late-generation rsd mutants, although defective spermatogenesis was insufficient to explain the majority of sterility. Increased expression of repetitive loci occurred in both germ and somatic cells of late-generation rsd mutant adults, suggesting that desilencing of many heterochromatic segments of the genome contributes to sterility. Nuclear RNAi defective (NRDE)-2 promotes nuclear silencing in response to exogenous double-stranded RNA, and our data imply that RSD-2, RSD-6, and NRDE-2 function in a common transgenerational nuclear silencing pathway that responds to endogenous siRNAs. We propose that RSD-2 and RSD-6 promote germ cell immortality at stressful temperatures by maintaining transgenerational epigenetic inheritance of endogenous siRNA populations that promote genome silencing. PMID:25258416

  10. Reversible immortalization of Nestin-positive precursor cells from pancreas and differentiation into insulin-secreting cells

    International Nuclear Information System (INIS)

    Highlights: ► The NPPCs from mouse pancreas were isolated. ► Tet-on system for SV40 large in NPPCs was used to get RINPPCs. ► The RINPPCs can undergo at least 80 population doublings without senescence. ► The RINPPCs can be induced to differentiate into insulin-producing cells. ► The combination of GLP-1 and sodium butyrate promoted the differentiation process. -- Abstract: Pancreatic stem cells or progenitor cells posses the ability of directed differentiation into pancreatic β cells. However, these cells usually have limited proliferative capacity and finite lifespan in vitro. In the present study, Nestin-positive progenitor cells (NPPCs) from mouse pancreas that expressed the pancreatic stem cells or progenitor cell marker Nestin were isolated to obtain a sufficient number of differentiated pancreatic β cells. Tet-on system for SV40 large T-antigen expression in NPPCs was used to achieve reversible immortalization. The reversible immortal Nestin-positive progenitor cells (RINPPCs) can undergo at least 80 population doublings without senescence in vitro while maintaining their biological and genetic characteristics. RINPPCs can be efficiently induced to differentiate into insulin-producing cells that contain a combination of glucagon-like peptide-1 (GLP-1) and sodium butyrate. The results of the present study can be used to explore transplantation therapy of type I diabetes mellitus.

  11. Reversible immortalization of Nestin-positive precursor cells from pancreas and differentiation into insulin-secreting cells

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Pei; Li, Li; Qi, Hui [The Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People' s Hospital), Jinan University, 518020 Shenzhen (China); Zhou, Han-xin [Department of General Surgery, First Hospital (Shenzhen Second People' s Hospital) of Shenzhen University, 518020 Shenzhen (China); Deng, Chun-yan [The Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People' s Hospital), Jinan University, 518020 Shenzhen (China); Li, Fu-rong, E-mail: frli62@yahoo.com [The Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People' s Hospital), Jinan University, 518020 Shenzhen (China); Shenzhen Institution of Gerontology, 518020 Shenzhen (China)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer The NPPCs from mouse pancreas were isolated. Black-Right-Pointing-Pointer Tet-on system for SV40 large in NPPCs was used to get RINPPCs. Black-Right-Pointing-Pointer The RINPPCs can undergo at least 80 population doublings without senescence. Black-Right-Pointing-Pointer The RINPPCs can be induced to differentiate into insulin-producing cells. Black-Right-Pointing-Pointer The combination of GLP-1 and sodium butyrate promoted the differentiation process. -- Abstract: Pancreatic stem cells or progenitor cells posses the ability of directed differentiation into pancreatic {beta} cells. However, these cells usually have limited proliferative capacity and finite lifespan in vitro. In the present study, Nestin-positive progenitor cells (NPPCs) from mouse pancreas that expressed the pancreatic stem cells or progenitor cell marker Nestin were isolated to obtain a sufficient number of differentiated pancreatic {beta} cells. Tet-on system for SV40 large T-antigen expression in NPPCs was used to achieve reversible immortalization. The reversible immortal Nestin-positive progenitor cells (RINPPCs) can undergo at least 80 population doublings without senescence in vitro while maintaining their biological and genetic characteristics. RINPPCs can be efficiently induced to differentiate into insulin-producing cells that contain a combination of glucagon-like peptide-1 (GLP-1) and sodium butyrate. The results of the present study can be used to explore transplantation therapy of type I diabetes mellitus.

  12. Immortal Ring-Opening Polymerization of rac-Lactide Using Polymeric Alcohol as Initiator to Prepare Graft Copolymer

    Directory of Open Access Journals (Sweden)

    Na Liu

    2016-01-01

    Full Text Available In the presence of a small molecular protic initiator, immortal ring-opening polymerization (ROP of lactide (LA is a highly efficient strategy to synthesize polylactide in a controllable manner, while using polymeric alcohol as an initiator has been less investigated. A series of polymeric alcohols (PS–OH composed of styrene and 4.3%–18% hydroxyl functional styrene (diethyl(hydroxy(4-vinylphenylmethylphosphonate, St–OH were synthesized through reversible addition-fragmentation transfer (RAFT polymerization. Using PS–OH as an initiator, the immortal ROP of rac-LA was catalyzed by dibutylmagnesium (MgnBu2 under various ratios of monomer to hydroxyl group within PS–OH to generate polystyrene-g-polylactide (PS–g–PLA copolymers with different graft lengths. After thermal annealing at 115 °C, the PLA domain aggregated to nanospheres among the PS continuum. The size of the nanospheres, varying from 130.1 to 224.2 nm, was related to the graft density and length of PS–g–PLA. Nanoporous films were afforded through chemical etching of the PLA component.

  13. Genetic effect of low dose rate radiation on human cells immortalized with the hTERT gene

    International Nuclear Information System (INIS)

    We established immortal human cells by introducing the hTERT gene into skin fibroblast cells obtained from normal (SuSa) and ataxia telangiectasia (AT: AT1OS) individuals of Japanese origin. These immortalized cells showed the same characteristics as the original cells except expanded life span. We irradiated SuSa/T-n and AT1OS/T-n cells with low-dose-rate (LDR; 0.3 mGy/min) irradiation at confluent state in low-serum medium. Then, survival rate and micronucleus frequency of each cell line were analyzed. In SuSa/T-n cells, frequency of HPRT mutation induction was also determined by 6TG selection. In SuSa/T-n cells, survival rate and micronucleus frequency showed higher resistance after irradiation with LDR than high-dose-rate (HDR; 2 Gy/min) irradiation. In contrast, no significant difference was observed in survival and micronucleus induction in AT1OS/T-n cells between HDR and LDR irradiation, suggesting that AT1OS/T-n cells may have some defect in DNA repair activity. In SuSa/T-n cells, the frequency of HPRT mutation after LDR irradiation decreased to approximately one eighth that after HDR irradiation. (author)

  14. Immortal Temple of South Sea-The Witness of Ancient Marine Trade in Guangzhou%广州古代海路贸易的见证者——南海神庙

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Immortal Temple of South Sea was the biggest, most integrated and unique architecture group of ancient sea Immortal temple. Located in Miaotou village, Huangpu,Guangzhou city, it is magnificent, simple and unsophisticated. The major building is a five-layer hall, from south to north lying Head Door, Yi Door, Double Roofed Corridor, Li Pavilion, Great Hall and Zhaoling Palace.

  15. Heat transport by turbulent Rayleigh-B\\'enard convection for $\\Pra\\ \\simeq 0.8$ and $4\\times 10^{11} \\alt \\Ra\\ \\alt 2\\times10^{14}$: Ultimate-state transition for aspect ratio $\\Gamma = 1.00$

    CERN Document Server

    He, Xiaozhou; Bodenschatz, Eberhard; Ahlers, Guenter

    2012-01-01

    We report experimental results for heat-transport measurements by turbulent Rayleigh-B\\'enard convection in a cylindrical sample of aspect ratio $\\Gamma \\equiv D/L = 1.00$ ($D = 1.12$ m is the diameter and $L = 1.12$ m the height). They are for the Rayleigh-number range $4\\times10^{11} \\alt \\Ra \\alt 2\\times10^{14}$ and for Prandtl numbers \\Pra\\ between 0.79 and 0.86. For $\\Ra \\Ra_1^*$ the data rise above the classical-state power-law and show greater scatter. In analogy to similar behavior observed for $\\Gamma = 0.50$, we interpret this observation as the onset of the transition to the ultimate state. Within our resolution this onset occurs at nearly the same value of $\\Ra_1^*$ as it does for $\\Gamma = 0.50$. This differs from an earlier estimate by Roche {\\it et al.} which yielded a transition at $\\Ra_U \\simeq 1.3\\times 10^{11} \\Gamma^{-2.5\\pm 0.5}$. A $\\Gamma$-independent $\\Ra^*_1$ would suggest that the boundary-layer shear transition is induced by fluctuations on a scale less than the sample dimensions r...

  16. Revised cutoff values of ALT and HBV DNA level can better differentiate HBeAg (- chronic inactive HBV patients from active carriers

    Directory of Open Access Journals (Sweden)

    Gull Sana

    2011-02-01

    Full Text Available Abstract Background and Aims ELISA is still used as primary test for diagnosis HBV disease. However, ELISA-positive patients were marked as HBV inactive after confirmation with PCR and vice versa. Our aim was to assess the performance of new cut-off value of ALT, HBV DNA load and significance of AST as screening tool for HBeAg (- chronic active or inactive patients in Pakistani population. Materials and methods In a cross-sectional, cohort study, 567 HBeAg (- patients followed for one year were selected. Patients with persistent elevated ALT than normal and HBV DNA ≥ 100,000 copies/mL were taken as active chronic. Diagnostic values for ALT, AST and HBV DNA load in HBV HBeAg (- chronic active and inactive patients compared using receiver operation characteristic (ROC curves. Results Of 567 HBeAg (- patients, 228 were classified as chronic inactive and 339 as active. HBV infection was dominant in male. Serum ALT, AST and HBV DNA levels showed significant and high AUROC to differentiate chronic HBeAg (- inactive patients from active. AUROC for Serum ALT, AST and HBV DNA were observed 0.997, 0.969 and 1.000, respectively. For revised cut off value for ALT (30 IU/L for male and 19 IU/L for female and HBV DNA load ≥100,000 copies/mL, a PPV of 97%, NPV of 94%, a sensitivity of 98%, and a specificity of 92% was observed to discriminate active carriers from inactive carriers. We also observed 93.5% specificity, 83.1% sensitivity, 82% PPV and 89.5% NPV for AST ≤20 IU/L to differentiate inactive carriers from active ones in our study group. Conclusions Revised cut off value of ALT and NIH derived HBV DNA value can better discriminate between HBeAg (- chronic active and inactive patients.

  17. ELEVATED ALANINE AMINOTRANSFERASE (ALT IN BLOOD DONORS: AN ASSESSMENT OF THE MAIN ASSOCIATED CONDITIONS AND ITS RELATIONSHIP TO THE DEVELOPMENT OF HEPATITIS C

    Directory of Open Access Journals (Sweden)

    Fernando Lopes GONÇALES Jr.

    1998-07-01

    Full Text Available The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH. The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87% had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1% donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9% had mild chronic active non A-G viral

  18. Perspectives on Immortality and Eternal Life in the Book of Wisdom and the Gospel of John: A Conceptual Analysis Based on Metaphorical Structuring

    NARCIS (Netherlands)

    Valentin, R.I.

    2016-01-01

    The similarities between the Fourth Gospel and wisdom literature have been addressed by many scholars. This study is also intended to continue along this line by looking at the particular link between the Wisdom of Solomon and the Gospel of John with a specific focus on the concepts of immortality a

  19. The G-quadruplex ligand telomestatin impairs binding of topoisomerase IIIalpha to G-quadruplex-forming oligonucleotides and uncaps telomeres in ALT cells.

    Directory of Open Access Journals (Sweden)

    Nassima Temime-Smaali

    Full Text Available In Alternative Lengthening of Telomeres (ALT cell lines, specific nuclear bodies called APBs (ALT-associated PML bodies concentrate telomeric DNA, shelterin components and recombination factors associated with telomere recombination. Topoisomerase IIIalpha (Topo III is an essential telomeric-associated factor in ALT cells. We show here that the binding of Topo III to telomeric G-overhang is modulated by G-quadruplex formation. Topo III binding to G-quadruplex-forming oligonucleotides was strongly inhibited by telomestatin, a potent and specific G-quadruplex ligand. In ALT cells, telomestatin treatment resulted in the depletion of the Topo III/BLM/TRF2 complex and the disruption of APBs and led to the segregation of PML, shelterin components and Topo III. Interestingly, a DNA damage response was observed at telomeres in telomestatin-treated cells. These data indicate the importance of G-quadruplex stabilization during telomere maintenance in ALT cells. The function of TRF2/Topo III/BLM in the resolution of replication intermediates at telomeres is discussed.

  20. Man should not let death attain the dominion of his thoughts: An Essay on Subjectivity, Self-Preservation and Immortality

    Directory of Open Access Journals (Sweden)

    Kasper Lysemose

    2010-12-01

    Full Text Available Mortality seems to have no place in the theories on subjectivity in Kant and Husserl. It is suggested that this entente cordiale is an expression of the shared principle at the heart of their philosophy, i.e. the principle of selfpreservation. Self-preservation is a principle that in a certain sense excludes mortality. It is argued that the primary sense of this exclusion is not theoretical but practical. Kant and Husserl are both endorsing the imperative that man should not let death attain the dominion of his thoughts (cf. Mann 1976, 600. The positive correlate to this is to be found in the demand that man should think of himself as if he was immortal. With special regard to Husserl the predicament that accompanies his relentless attempt to fulfill this demand is described as a sluice through which anthropology threatens to flow into the phenomenological enterprise.

  1. Myth about immortality in the contemporary pop culture: A case study about Toše Proeski

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    Stevanović Lada

    2013-01-01

    Full Text Available This paper explores the intersection of death and ideology in the sphere of popular culture, as exemplified by the afterlife destiny of Toše Proeski, a Macedonian pop singer whose huge popularity continued even after his death. His sudden, untimely death in his twenties had exploded as huge news, preoccupying all sorts of media. What I am interested in this paper is what has happened afterwards. In which way his popularity and his afterlife continue? Can we identify some kind of pop hero cult here, and is it possible to recognize common elements, or even a pattern according to which (newborn stars develop an afterlife destiny? Can we use this opportunity to discuss immortality myths? Do pop stars get monuments or are these reserved just for national heroes?

  2. A telomerase immortalized human proximal tubule cell line with a truncation mutation (Q4004X in polycystin-1.

    Directory of Open Access Journals (Sweden)

    Brittney-Shea Herbert

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is associated with a variety of cellular phenotypes in renal epithelial cells. Cystic epithelia are secretory as opposed to absorptive, have higher proliferation rates in cell culture and have some characteristics of epithelial to mesenchymal transitions. In this communication we describe a telomerase immortalized cell line that expresses proximal tubule markers and is derived from renal cysts of an ADPKD kidney. These cells have a single detectable truncating mutation (Q4004X in polycystin-1. These cells make normal appearing but shorter cilia and fail to assemble polycystin-1 in the cilia, and less uncleaved polycystin-1 in membrane fractions. This cell line has been maintained in continuous passage for over 35 passages without going into senescence. Nephron segment specific markers suggest a proximal tubule origin for these cells and the cell line will be useful to study mechanistic details of cyst formation in proximal tubule cells.

  3. Sensitive Tumorigenic Potential Evaluation of Adult Human Multipotent Neural Cells Immortalized by hTERT Gene Transduction

    Science.gov (United States)

    Jeong, Da Eun; Kim, Sung Soo; Song, Hye Jin; Pyeon, Hee Jang; Kang, Kyeongjin; Hong, Seung-Cheol; Nam, Do-Hyun; Joo, Kyeung Min

    2016-01-01

    Stem cells and therapeutic genes are emerging as a new therapeutic approach to treat various neurodegenerative diseases with few effective treatment options. However, potential formation of tumors by stem cells has hampered their clinical application. Moreover, adequate preclinical platforms to precisely test tumorigenic potential of stem cells are controversial. In this study, we compared the sensitivity of various animal models for in vivo stem cell tumorigenicity testing to identify the most sensitive platform. Then, tumorigenic potential of adult human multipotent neural cells (ahMNCs) immortalized by the human telomerase reverse transcriptase (hTERT) gene was examined as a stem cell model with therapeutic genes. When human glioblastoma (GBM) cells were injected into adult (4–6-week-old) Balb/c-nu, adult NOD/SCID, adult NOG, or neonate (1–2-week-old) NOG mice, the neonate NOG mice showed significantly faster tumorigenesis than that of the other groups regardless of intracranial or subcutaneous injection route. Two kinds of ahMNCs (682TL and 779TL) were primary cultured from surgical samples of patients with temporal lobe epilepsy. Although the ahMNCs were immortalized by lentiviral hTERT gene delivery (hTERT-682TL and hTERT-779TL), they did not form any detectable masses, even in the most sensitive neonate NOG mouse platform. Moreover, the hTERT-ahMNCs had no gross chromosomal abnormalities on a karyotype analysis. Taken together, our data suggest that neonate NOG mice could be a sensitive animal platform to test tumorigenic potential of stem cell therapeutics and that ahMNCs could be a genetically stable stem cell source with little tumorigenic activity to develop regenerative treatments for neurodegenerative diseases. PMID:27391353

  4. Sensitive Tumorigenic Potential Evaluation of Adult Human Multipotent Neural Cells Immortalized by hTERT Gene Transduction.

    Directory of Open Access Journals (Sweden)

    Kee Hang Lee

    Full Text Available Stem cells and therapeutic genes are emerging as a new therapeutic approach to treat various neurodegenerative diseases with few effective treatment options. However, potential formation of tumors by stem cells has hampered their clinical application. Moreover, adequate preclinical platforms to precisely test tumorigenic potential of stem cells are controversial. In this study, we compared the sensitivity of various animal models for in vivo stem cell tumorigenicity testing to identify the most sensitive platform. Then, tumorigenic potential of adult human multipotent neural cells (ahMNCs immortalized by the human telomerase reverse transcriptase (hTERT gene was examined as a stem cell model with therapeutic genes. When human glioblastoma (GBM cells were injected into adult (4-6-week-old Balb/c-nu, adult NOD/SCID, adult NOG, or neonate (1-2-week-old NOG mice, the neonate NOG mice showed significantly faster tumorigenesis than that of the other groups regardless of intracranial or subcutaneous injection route. Two kinds of ahMNCs (682TL and 779TL were primary cultured from surgical samples of patients with temporal lobe epilepsy. Although the ahMNCs were immortalized by lentiviral hTERT gene delivery (hTERT-682TL and hTERT-779TL, they did not form any detectable masses, even in the most sensitive neonate NOG mouse platform. Moreover, the hTERT-ahMNCs had no gross chromosomal abnormalities on a karyotype analysis. Taken together, our data suggest that neonate NOG mice could be a sensitive animal platform to test tumorigenic potential of stem cell therapeutics and that ahMNCs could be a genetically stable stem cell source with little tumorigenic activity to develop regenerative treatments for neurodegenerative diseases.

  5. Chitosan: poly(N-vinylpyrrolidone-alt-itaconic anhydride) nanocapsules—a promising alternative for the lung cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Raţă, Delia Mihaela, E-mail: iureadeliamihaela@yahoo.com [„Apollonia” University of Iasi, Faculty of Medical Dentistry, „Academician Ioan Haulică” Research Institute (Romania); Chailan, Jean-François, E-mail: chailan@univ-tln.fr [University of Sud Toulon-Var, « Matériaux-Polymères-Interfaces-Environnement Marin (MAPIEM) Laboratory (France); Peptu, Cătălina Anişoara, E-mail: catipeptu@yahoo.co.uk [“Gheorghe Asachi” Technical University of Iasi, Department of Natural and Synthetic Polymers, Faculty of Chemical Engineering and Environmental Protection (Romania); Costuleanu, Marcel, E-mail: mcostuleanu@yahoo.com [University of Medicine and Pharmacy “Grigore T. Popa”- Iaşi, Department of General Pathology, Faculty of Dental Medicine (Romania); Popa, Marcel, E-mail: marpopa2001@yahoo.fr [“Gheorghe Asachi” Technical University of Iasi, Department of Natural and Synthetic Polymers, Faculty of Chemical Engineering and Environmental Protection (Romania)

    2015-07-15

    This study reports the preparation of novel polymeric nanocapsules based on a natural polymer, chitosan and a synthetic one, poly(N-vinylpyrrolidone-alt-itaconic anhydride) [(poly(NVPAI)] using an interfacial condensation technique. The infrared spectroscopy studies confirmed the crosslinking through the presence of amide bonds, formed between the two polymers chains. The diameter of nanocapsules was found in the range of 126–214 nm and it was determined by dynamic light scattering method. Morphological characterization demonstrated their nano size, the spherical shape of the nanocapsules and the formation of hollow particles. The nanocapsules presented good swelling capacity in aqueous solutions. 5-Fluorouracil (5-FU) loading and release capacity was studied, the processes being controlled by the drug diffusion through the polymeric membrane. The obtained results were encouraging, showing that 5-FU-loaded nanocapsules had 70 % higher apoptotic effect on A549 tumour cells than the drug in free state or mixed with the nanocapsules.

  6. Chitosan: poly(N-vinylpyrrolidone-alt-itaconic anhydride) nanocapsules—a promising alternative for the lung cancer treatment

    International Nuclear Information System (INIS)

    This study reports the preparation of novel polymeric nanocapsules based on a natural polymer, chitosan and a synthetic one, poly(N-vinylpyrrolidone-alt-itaconic anhydride) [(poly(NVPAI)] using an interfacial condensation technique. The infrared spectroscopy studies confirmed the crosslinking through the presence of amide bonds, formed between the two polymers chains. The diameter of nanocapsules was found in the range of 126–214 nm and it was determined by dynamic light scattering method. Morphological characterization demonstrated their nano size, the spherical shape of the nanocapsules and the formation of hollow particles. The nanocapsules presented good swelling capacity in aqueous solutions. 5-Fluorouracil (5-FU) loading and release capacity was studied, the processes being controlled by the drug diffusion through the polymeric membrane. The obtained results were encouraging, showing that 5-FU-loaded nanocapsules had 70 % higher apoptotic effect on A549 tumour cells than the drug in free state or mixed with the nanocapsules

  7. Liver stiffness measurement and biochemical markers in Senegalese chronic hepatitis B patients with normal ALT and high viral load.

    Directory of Open Access Journals (Sweden)

    Papa Saliou Mbaye

    Full Text Available BACKGROUND AND AIMS: Despite the high prevalence of chronic hepatitis B (CHB in Africa, few studies have been performed among African patients. We sought to evaluate liver stiffness measurement by FibroScan® (LSM and two biochemical scores (FibroTest®, Fibrometer® to diagnose liver fibrosis in Senegalese CHB patients with HBV plasma DNA load ≥3.2 log(10 IU/mL and normal alanine aminotransferase (ALT values. METHODS: LSM and liver fibrosis biochemical markers were performed on 225 consecutive HBV infected Senegalese patients with high viral load. Patients with an LSM range between 7 and 13 kPa underwent liver biopsy (LB. Two experienced liver pathologists performed histological grading using Metavir and Ishak scoring. RESULTS: 225 patients were evaluated (84% male and LB was performed in 69 patients, showing F2 and F3 fibrosis in 17% and 10% respectively. In these patients with a 7-13 kPa range of LSM, accuracy for diagnosis of significant fibrosis according to LB was unsatisfactory for all non-invasive markers with AUROCs below 0.70. For patients with LSM values below 7 kPa, FibroTest® (FT, and Fibrometer® (FM using the cut-offs recommended by the test promoters suggested a fibrosis in 18% of cases for FT (8% severe fibrosis and 8% for FM. For patients with LSM values greater than 13 kPa, FT, FM suggested a possible fibrosis in 73% and 70%, respectively. CONCLUSION: In highly replicative HBV-infected African patients with normal ALT and LSM value below 13 kPa, FibroScan®, FibroTest® or Fibrometer® were unsuitable to predict the histological liver status of fibrosis.

  8. An integrated program of geophysical survey, coring, and test excavations to study a 4th millennium bc-cal ditch at Alt del Punxó (Muro de L’alcoi, Alacant

    Directory of Open Access Journals (Sweden)

    García Puchol, Otero

    2008-06-01

    Full Text Available The potentially long and interesting archaeological sequence revealed by systematic survey at the site of Alt Del Punxó (Muro de l’Alcoi, Alacant was the basis for initiating a study of the locality’s subsurface structures using new methods of remote sensing. Geophysical survey (magnetometry and tomography and systematic augering revealed buried structures, including monumental earthworks, and guided subsequent excavations to collect more detailed data about the nature and age of these prehistoric features. The information recovered, including new radiocarbon dates, offers a new perspective on the organization of prehistoric populations in this region of south-central Valencia since the beginning of the Holocene and is especially important for understanding the Neolithic IIB from the 4th through the early 3rd Millennium BC.

    La amplia e interesante secuencia arqueológica sugerida por los materiales de superficie del yacimiento de Alt del Punxó (Muro de l’Alcoi, Alacant ha supuesto el punto de partida para la práctica de una serie de métodos de detección de las estructuras conservadas en el lugar. La prospección geofísica (magnetometría y tomografía, y los microsondeos (augers han dirigido la planificación de la excavación con el fin de obtener nuevos datos a propósito de la naturaleza y cronología del gran foso prehistórico, así como de las diversas estructuras localizadas. La información obtenida, junto a la serie radiocarbónica disponible, abre nuevas perspectivas para el estudio del poblamiento prehistórico al aire libre en las comarcas centro-meridionales valencianas desde los inicios del Holoceno, y de un modo particular en el IV e inicios del III milenio cal AC –Neolítico IIB.

  9. Krása a nesmrteľnosť. O plodení u Platóna a Shakespeara (Beauty and Immortality. On Procreation in Plato and Shakespeare)

    OpenAIRE

    Anton Vydra

    2007-01-01

    There are two moments referred in this essay: (1) A human being, which desires for immortality, desires for to be alive in his child or in an artwork. (2) Full human being’s desire is related for beauty. Is a beauty the same thing as immortality? How looks the relation between them? Shakespeare’s Sonnets begin with the challenge to his friend to procreate the offspring, because this is a way for immortality of the friend’s beauty. And if it is not a child, than verse refused him before the de...

  10. Long term follow-up and patterns of response of ALT in patients with chronic hepatitis NANB/C treated with recombinant interferon-alpha Seguimento tardio e padrões de resposta da ALT em pacientes com hepatite crônica NANB/C tratados com interferon-alfa

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    L.C. da Silva

    1995-06-01

    Full Text Available The response to interferon treatment in chronic hepatitis NANB/C has usually been classified as complete, partial or absent, according to the behavior of serum alanine aminotransferase (ALT. However, a more detailed observation of the enzymatic activity has shown that the patterns may be more complex. The aim of this study was to describe the long term follow-up and patterns of ALT response in patients with chronic hepatitis NANB/C treated with recombinant interferon-alpha. A follow-up of 6 months or more after interferon-a was achieved in 44 patients. We have classified the serum ALT responses into six patterns and the observed frequencies were as follows: I. Long term response = 9 (20.5%; II. Normalization followed by persistent relapse after IFN = 7 (15.9%; III. Normalization with transient relapse = 5 (11.9%; IV. Temporary normalization and relapse during IFN = 4 (9.1%; V. Partial response (more than 50% of ALT decrease = 7 (15.9%; VI. No response = 12 (27.3%. In conclusion, ALT patterns vary widely during and after IFN treatment and can be classified in at least 6 types.A resposta ao tratamento com interferon em pacientes com hepatite crônica NANB/C tem sido classificada como completa, parcial ou ausente, de acordo com o comportamento da alanino aminotransferase sérica (ALT. Entretanto, uma observação mais detalhada da atividade enzimática tem mostrado que os padrões podem ser mais complexos. O objetivo deste estudo foi descrever o seguimento tardio e os padrões de resposta da ALT em pacientes com hepatite crônica NANB/C tratados com interferon alfa recombinante. Classificamos os tipos de resposta da ALT em 6 padrões e as freqüências observadas foram:I. Resposta completa e persistente = 9 (20,5%; II. Resposta completa com recaída persistente após o IFN = 7 (15,9%; III. Resposta completa com recaída temporária = 5 (11,9%; IV. Normalização temporária e recaída durante o tratamento com IFN = 4 (9,1%; V. Resposta parcial

  11. A Polyphenol-Enriched Fraction of Rose Oil Distillation Wastewater Inhibits Cell Proliferation, Migration and TNF-α-Induced VEGF Secretion in Human Immortalized Keratinocytes.

    Science.gov (United States)

    Wedler, Jonas; Rusanov, Krasimir; Atanassov, Ivan; Butterweck, Veronika

    2016-07-01

    Water steam distillation of rose flowers separates the essential oil from the polyphenol-containing rose oil distillation wastewater. Recently, a strategy was developed to separate rose oil distillation wastewater into a polyphenol depleted water fraction and a polyphenol-enriched fraction [RF20-(SP-207)]. The objective of the present study was to investigate RF20-(SP-207) and fraction F(IV), augmented in quercetin and ellagic acid, for possible antiproliferative effects in immortalized human keratinocytes (HaCaT) since rose petals are known to contain compounds with potential antiproliferative activity.RF20-(SP-207) revealed dose-dependent antiproliferative activity (IC50 of 9.78 µg/mL). In a nontoxic concentration of 10 µg/mL, this effect was stronger than that of the two positive controls LY294002 (10 µM, PI3 K-inhibitor, 30 % inhibition) and NVP-BEZ235 (100 nM, dual PI3 K/mTOR inhibitor, 30 % inhibition) and clearly exceeded the antiproliferative action of quercetin (50 µM, 25 % inhibition) and ellagic acid (1 µM, 15 % inhibition). Time-lapse microscopy detected a significant impairment of cell migration of RF20-(SP-207) and F(IV). At concentrations of 10 µg/mL of both, extract and fraction, cell migration was strongly suppressed (51 % and 28 % gap closure, respectively, compared to 95 % gap closure 24 hours after control treatment). The suppression of cell migration was comparable to the positive controls LY294002, NVP-BEZ235, and quercetin. Furthermore, basal and TNF-α-stimulated VEGF-secretion was significantly reduced by RF20-(SP-207) and F(IV) at 10 µg/mL (44 % vs. untreated control).In conclusion, RF20-(SP-207) showed promising antiproliferative and antimigratory effects and could be developed as a supportive, therapy against hyperproliferation-involved skin diseases. PMID:27093251

  12. AltMV TGB1 nucleolar localization requires homologous interaction and correlates with cell wall localization associated with cell-to-cell movement

    Science.gov (United States)

    The Potexvirus Alternanthera mosaic virus has multifunctional triple gene block (TGB) proteins, among which our studies have focused on the properties of the TGB1 protein. The TGB1 of AltMV has functions including RNA binding, RNA silencing suppression, and cell-to-cell movement, and is known to for...

  13. AlBer : Protocole de caractérisation des Altérations des Berges (version 2012.1). Rapport final

    OpenAIRE

    Alleaume, S.; Lanoiselee, C.; Argillier, C.

    2012-01-01

    This paper proposes a protocol for characterizing the lakes’ riparian alterations based on photo-interpretation coupled with field observations. / Ce document propose un protocole de caractérisation des altérations des berges des plans d’eau basé sur une photo-interprétation d’orthophotos associée à des observations de terrain.

  14. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  15. Revealed Attention

    OpenAIRE

    Masatlioglu, Yusufcan; NAKAJIMA, Daisuke; Ozbay, Erkut Y

    2012-01-01

    The standard revealed preference argument relies on an implicit assumption that a decision maker considers all feasible alternatives. The marketing and psychology literatures, however, provide wellestablished evidence that consumers do not consider all brands in a given market before making a purchase (Limited Attention). In this paper, we illustrate how one can deduce both the decision maker's preference and the alternatives to which she pays attention and inattention from the observed behav...

  16. Revealed Attention

    OpenAIRE

    Yusufcan Masatlioglu; Daisuke Nakajima; Ozbay, Erkut Y

    2012-01-01

    The standard revealed preference argument relies on an implicit assumption that a decision maker considers all feasible alternatives. The marketing and psychology literatures, however, provide well-established evidence that consumers do not consider all brands in a given market before making a purchase (Limited Attention). In this paper, we illustrate how one can deduce both the decision maker's preference and the alternatives to which she pays attention and inattention from the observed beha...

  17. β-adrenergic receptor activation in immortalized human urothelial cells stimulates inflammatory responses by PKA-independent mechanisms

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    Porter James E

    2005-08-01

    Full Text Available Abstract Background Interstitial cystitis (IC is a debilitating disease characterized by chronic inflammation of the urinary bladder, yet specific cellular mechanisms of inflammation in IC are largely unknown. Multiple lines of evidence suggest that β-adrenergic receptor (AR signaling is increased in the inflamed urothelium, however the precise effects of these urothelial cell signals have not been studied. In order to better elucidate the AR signaling mechanisms of inflammation associated with IC, we have examined the effects of β-AR stimulation in an immortalized human urothelial cell line (UROtsa. For these studies, UROtsa cells were treated with effective concentrations of the selective β-AR agonist isoproterenol, in the absence or presence of selective inhibitors of protein kinase A (PKA. Cell lysates were analyzed by radioimmunoassay for generation of cAMP or by Western blotting for induction of protein products associated with inflammatory responses. Results Radioligand binding demonstrated the presence of β-ARs on human urothelial UROtsa cell membranes. Stimulating UROtsa cells with isoproterenol led to concentration-dependent increases of cAMP production that could be inhibited by pretreatment with a blocking concentration of the selective β-AR antagonist propranolol. In addition, isoproterenol activation of these same cells led to significant increases in the amount of phosphorylated extracellular signal-regulated kinase (pERK, inducible nitric oxide synthase (iNOS and the induced form of cyclooxygenase (COX-2 when compared to control. Moreover, preincubation of UROtsa cells with the selective PKA inhibitors H-89 or Rp-cAMPs did not diminish this isoproterenol mediated phosphorylation of ERK or production of iNOS and COX-2. Conclusion Functional β-ARs expressed on human urothelial UROtsa cell membranes increase the generation of cAMP and production of protein products associated with inflammation when activated by the selective

  18. Cell-based assay for the detection of chemically induced cellular stress by immortalized untransformed transgenic hepatocytes

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    Vezzoni Paolo

    2004-03-01

    Full Text Available Abstract Background Primary hepatocytes, one of the most widely used cell types for toxicological studies, have a very limited life span and must be freshly derived from mice or even humans. Attempts to use stable cell lines maintaining the enzymatic pattern of liver cells have been so far unsatisfactory. Stress proteins (heat shock proteins, HSPs have been proposed as general markers of cellular injury and their use for environmental monitoring has been suggested. The aim of this work is to develop a bi-transgenic hepatocyte cell line in order to evaluate the ability of various organic and inorganic chemicals to induce the expression of the HSP70 driven reporter gene. We previously described transgenic mice (Hsp70/hGH secreting high levels of human Growth Hormone (hGH following exposure to toxic compounds in vivo and in vitro in primary cultures derived from different organs. In addition, we also reported another transgenic model (AT/cytoMet allowing the reproducible immortalization of untransformed hepatocytes retaining in vitro complex liver functions. Results The transgenic mouse line Hsp70/hGH was crossed with the AT/cytoMet transgenic strain permitting the reproducible immortalization of untransformed hepatocytes. From double transgenic animals we derived several stable hepatic cell lines (MMH-GH which showed a highly-differentiated phenotype as judged from the retention of epithelial cell polarity and the profile of gene expression, including hepatocyte-enriched transcription factors and detoxifying enzymes. In these cell lines, stresses induced by exposure to inorganic [Sodium Arsenite (NaAsO2 and Cadmium Chloride (CdCl2], and organic [Benzo(aPyrene (BaP, PentaChloroPhenol (PCP, TetraChloroHydroQuinone (TCHQ, 1-Chloro-2,4-DiNitro-Benzene (CDNB] compounds, specifically induced hGH release in the culture medium. Conclusions MMH-GH, an innovative model to evaluate the toxic potential of chemical and physical xenobiotics, provides a simple

  19. Characterization of a novel telomerase-immortalized human endometrial stromal cell line, St-T1b

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    Brosens Jan J

    2009-07-01

    Full Text Available Abstract Background Coordinated differentiation of the endometrial compartments in the second half of the menstrual cycle is a prerequisite for the establishment of pregnancy. Endometrial stromal cells (ESC decidualize under the influence of ovarian progesterone to accommodate implantation of the blastocyst and support establishment of the placenta. Studies into the mechanisms of decidualization are often hampered by the lack of primary ESC. Here we describe a novel immortalized human ESC line. Methods Primary ESC were immortalized by the transduction of telomerase. The resultant cell line, termed St-T1b, was characterized for its morphological and biochemical properties by immunocytochemistry, RT-PCR and immunoblotting. Its progestational response was tested using progesterone and medroxyprogesterone acetate with and without 8-Br-cAMP, an established inducer of decidualization in vitro. Results St-T1b were positive for the fibroblast markers vimentin and CD90 and negative for the epithelial marker cytokeratin-7. They acquired a decidual phenotype indistinguishable from primary ESC in response to cAMP stimulation. The decidual response was characterized by transcriptional activation of marker genes, such as PRL, IGFBP1, and FOXO1, and enhanced protein levels of the tumor suppressor p53 and the metastasis suppressor KAI1 (CD82. Progestins alone had no effect on St-T1b cells, but medroxyprogesterone acetate greatly enhanced the cAMP-stimulated expression of IGFBP-1 after 3 and 7 days. Progesterone, albeit more weakly, also augmented the cAMP-induced IGFBP-1 production but only after 7 days of treatment. The cell line remained stable in continuous culture for more than 150 passages. Conclusion St-T1b express the appropriate phenotypic ESC markers and their decidual response closely mimics that of primary cultures. Decidualization is efficiently induced by cAMP analog and enhanced by medroxyprogesterone acetate, and, to a lesser extent, by natural

  20. Establishment of a luciferase assay-based screening system: Fumitremorgin C selectively inhibits cellular proliferation of immortalized astrocytes expressing an active form of AKT

    International Nuclear Information System (INIS)

    The AKT pathway is frequently activated in glioblastoma, and as such, inhibitors of this pathway could prove very useful as anti-glioblastoma therapies. Here we established immortalized astrocytes expressing Renilla luciferase as well as those expressing both an active form of AKT and firefly luciferase. Since both luciferase activities represent the numbers of corresponding cell lines, novel inhibitors of the AKT pathway can be identified by treating co-cultures containing the two types of luciferase-expressing cells with individual compounds. Indeed, such a screening system succeeded in identifying fumitremorgin C as an efficient inhibitor of the AKT pathway, which was further confirmed by the ability of fumitremorgin C to selectively inhibit the growth of immortalized astrocytes expressing an active form of AKT. The present study proposes a broadly applicable approach for identifying therapeutic agents that target the pathways and/or molecules responsible for cancer development

  1. BOOK REVIEW: LOREDANA-MARIA ILIN-GROZOIU: CONCEPTS, BELIEFS AND TRADITIONS REGARDING THE IMMORTALITY OF THE SOUL AND THE CULT OF DEADS

    OpenAIRE

    Georgeta GHIONEA

    2015-01-01

    In the same time a synthesis and a working instrument, the work Concepts, Beliefs and Traditions Regarding the Immortality of the Soul and the Cult of Deads, is the result of many researches and investigated details, the intention of the author being that to comprise as much information as possible, and to present them to the reader, both from the ethnographic, and also expositive and interpretative perspective. The work contains a Foreword, three chaptle Conclusions and a Selective bibliogra...

  2. Differentiation of the immortalized adult neuronal progenitor cell line HC2S2 into neurons by regulatable suppression of the v-myc oncogene.

    OpenAIRE

    Hoshimaru, M; Ray, J.; Sah, D W; Gage, F.H.

    1996-01-01

    A regulatable retroviral vector in which the v-myc oncogene is driven by a tetracycline-controlled transactivator and a human cytomegalovirus minimal promoter fused to a tet operator sequence was used for conditional immortalization of adult rat neuronal progenitor cells. A single clone, HC2S2, was isolated and characterized. Two days after the addition of tetracycline, the HC2S2 cells stopped proliferating, began to extend neurites, and expressed the neuronal markers tau, NeuN, neurofilament...

  3. Large-scale analysis of protein expression changes in human keratinocytes immortalized by human papilloma virus type 16 E6 and E7 oncogenes

    Directory of Open Access Journals (Sweden)

    Arnouk Hilal

    2009-08-01

    Full Text Available Abstract Background Infection with high-risk type human papilloma viruses (HPVs is associated with cervical carcinomas and with a subset of head and neck squamous cell carcinomas. Viral E6 and E7 oncogenes cooperate to achieve cell immortalization by a mechanism that is not yet fully understood. Here, human keratinocytes were immortalized by long-term expression of HPV type 16 E6 or E7 oncoproteins, or both. Proteomic profiling was used to compare expression levels for 741 discrete protein features. Results Six replicate measurements were performed for each group using two-dimensional difference gel electrophoresis (2D-DIGE. The median within-group coefficient of variation was 19–21%. Significance of between-group differences was tested based on Significance Analysis of Microarray and fold change. Expression of 170 (23% of the protein features changed significantly in immortalized cells compared to primary keratinocytes. Most of these changes were qualitatively similar in cells immortalized by E6, E7, or E6/7 expression, indicating convergence on a common phenotype, but fifteen proteins (~2% were outliers in this regulatory pattern. Ten demonstrated opposite regulation in E6- and E7-expressing cells, including the cell cycle regulator p16INK4a; the carbohydrate binding protein Galectin-7; two differentially migrating forms of the intermediate filament protein Cytokeratin-7; HSPA1A (Hsp70-1; and five unidentified proteins. Five others had a pattern of expression that suggested cooperativity between the co-expressed oncoproteins. Two of these were identified as forms of the small heat shock protein HSPB1 (Hsp27. Conclusion This large-scale analysis provides a framework for understanding the cooperation between E6 and E7 oncoproteins in HPV-driven carcinogenesis.

  4. Separator Membrane from Crosslinked Poly(Vinyl Alcohol and Poly(Methyl Vinyl Ether-alt-Maleic Anhydride

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    Charu Vashisth Rohatgi

    2015-03-01

    Full Text Available In this work, we report separator membranes from crosslinking of two polymers, such as poly vinyl alcohol (PVA with an ionic polymer poly(methyl vinyl ether-alt-maleic anhydride (PMVE-MA. Such interpolymer-networked systems were extensively used for biomedical and desalination applications but they were not examined for their potential use as membranes or separators for batteries. Therefore, the chemical interactions between these two polymers and the influence of such crosslinking on physicochemical properties of the membrane are systematically investigated through rheology and by critical gel point study. The hydrogen bonding and the chemical interaction between PMVE-MA and PVA resulted in highly cross-linked membranes. Effect of the molecular weight of PVA on the membrane properties was also examined. The developed membranes were extensively characterized by studying their physicochemical properties (water uptake, swelling ratio, and conductivity, thermal and electrochemical properties using differential scanning calorimetry (DSC, dynamic mechanical analysis (DMA, thermo-gravimetric analysis (TGA and electrochemical impedance spectroscopy (EIS. The DSC study shows the presence of a single Tg in the membranes indicating compatibility of the two polymers in flexible and transparent films. The membranes show good stability and ion conductivity suitable for separator applications.

  5. Frederick W. Alt received the 2015 Szent-Györgi Prize forProgress inCancer Research

    Institute of Scientific and Technical Information of China (English)

    PeterScully; JieZhao; SujuanBa

    2016-01-01

    The Szent-Györgyi Prize for Progress in Cancer Research is a prestigious scientiifc award established by the National Foundation for Cancer Research (NFCR)—a leading cancer research charitable organization in the United States that is committed to supporting scientiifc research and public education relating to the prevention, early diagnosis, better treatments, and ultimately, a cure for cancer. Each year, the Szent-Györgyi Prize honors an outstanding researcher, nominated by colleagues or peers, who has contributed outstanding, signiifcant research to the ifght against cancer, and whose accomplishments have helped improve treatment options for cancer patients. The Prize also promotes public awareness of the importance of basic cancer research and encourages the sustained investment needed to accelerate the translation of these research discoveries into new cancer treatments. This report highlights the pio-neering work led by the 2015 Prize winner, Dr. Frederick Alt. Dr. Alt’s work in the area of cancer genetics over four decades has helped to shape the very roots of modern cancer research. His work continues to profoundly impact the approaches that doctors around the globe use to diagnose and treat cancer. In particular, his seminal discoveries of gene ampliifcation and his pioneering work on molecular mechanisms of DNA damage repair have helped to usher in the era of genetically targeted therapy and personalized medicine.

  6. Altıntop Suyundaki Acılığın Naringinaz Enzimi ile Giderilmesi

    OpenAIRE

    Çeviker, Zuhal; Ünal, M. Ümit

    2005-01-01

    Bu çalışmada MarshSeedless ve Rio Red çeşiti altıntoplardan elde edilen meyve sularındaki acılığın giderilmesi araştırılmıştır. Acılık giderme işlemi farklı naringinaz konsantrasyonlarında (0.25, 0.50, 0.75 ve 1.00 g/L) ve farklı sıcaklıklarda (25, 35 ve 40oC) gerçekleştirilmiştir. Naringin giderimi, naringinaz miktarı ve sıcaklıktaki artışa paralel olarak artmıştır. Her iki çeşitte de en yüksek naringin giderimi 1 g/L naringinaz konsantrasyonunda 40oC’de ve 6 saatlik inkübasyon sonunda eld...

  7. The role of p38 MAP kinase and c-Jun N-terminal protein kinase signaling in the differentiation and apoptosis of immortalized neural stem cells

    International Nuclear Information System (INIS)

    The two distinct members of the mitogen-activated protein (MAP) kinase family c-Jun N-terminal protein kinase (JNK) and p38 MAP kinase, play an important role in central nervous system (CNS) development and differentiation. However, their role and functions are not completely understood in CNS. To facilitate in vitro study, we have established an immortal stem cell line using SV40 from fetal rat embryonic day 17. In these cells, MAP kinase inhibitors (SP600125, SB202190, and PD98059) were treated for 1, 24, 48, and 72 h to examine the roles of protein kinases. Early inhibition of JNK did not alter phenotypic or morphological changes of immortalized cells, however overexpression of Bax and decrease of phosphorylated AKT was observed. The prolonged inhibition of JNK induced polyploidization of immortalized cells, and resulted in differentiation and inhibition of cell proliferation. Moreover, JNK and p38 MAP kinase but not ERK1/2 was activated, and p21, p53, and Bax were overexpressed by prolonged inhibition of JNK. These results indicate that JNK and p38 MAP kinase could play dual roles on cell survival and apoptosis. Furthermore, this established cell line could facilitate study of the role of JNK and p38 MAP kinase on CNS development or differentiation/apoptosis

  8. Rare Circulating Cells in Familial Waldenstrom Macroglobulinemia Displaying the MYD88 L265P Mutation Are Enriched by Epstein-Barr Virus Immortalization.

    Directory of Open Access Journals (Sweden)

    Maroulio Pertesi

    Full Text Available The MYD88 L265P is a recurrent somatic mutation in neoplastic cells from patients with Waldenström Macroglobulinemia (WM. We identified the MYD88 L265P mutation in three individuals from unrelated families, but its presence did not explain the disease segregation within these WM pedigrees. We observed the mutation in these three individuals at high allele fractions in DNA extracted from EBV-immortalized Lymphoblastoid cell lines established from peripheral blood (LCL, but at much lower allele fractions in DNA extracted directly from peripheral blood, suggesting that this mutation is present in a clonal cell subpopulation rather than of germ-line origin. Furthermore, we observed that the MYD88 L265P mutation is enriched in WM families, detected in 40.5% of patients with familial WM or MGUS (10/22 WM, 5/15 MGUS, compared to 3.5% of patients with familial MM or MGUS (0/72 MM, 4/41 MGUS (p = 10-7. The mutant allele frequency increased with passages in vitro after immortalization with Epstein-Barr virus (EBV consistent with the MYD88 L265P described gain-of-function proposed for this mutation. The MYD88 L265P mutation appears to be frequently present in circulating cells in patients with WM, and MGUS, and these cells are amenable to immortalization by EBV.

  9. Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer.

    Science.gov (United States)

    Chen, Yi; Pirisi, Lucia; Creek, Kim E

    2013-09-01

    We compared the levels of the Ski oncoprotein, an inhibitor of transforming growth factor-beta (TGF-β) signaling, in normal human keratinocytes (HKc), HPV16 immortalized HKc (HKc/HPV16), and differentiation resistant HKc/HPV16 (HKc/DR) in the absence and presence of TGF-β. Steady-state Ski protein levels increased in HKc/HPV16 and even further in HKc/DR, compared to HKc. TGF-β treatment of HKc, HKc/HPV16, and HKc/DR dramatically decreased Ski. TGF-β-induced Ski degradation was delayed in HKc/DR. Ski and phospho-Ski protein levels are cell cycle dependent with maximal Ski expression and localization to centrosomes and mitotic spindles during G2/M. ShRNA knock down of Ski in HKc/DR inhibited cell proliferation. More intense nuclear and cytoplasmic Ski staining and altered Ski localization were found in cervical cancer samples compared to adjacent normal tissue in a cervical cancer tissue array. Overall, these studies demonstrate altered Ski protein levels, degradation and localization in HPV16-transformed human keratinocytes and in cervical cancer.

  10. Comparative QTL analysis of maize seed artificial aging between an immortalized F2 population and its corresponding RILs

    Institute of Scientific and Technical Information of China (English)

    Bin Wang; Zhanhui Zhang; Zhiyuan Fu; Zonghua Liu; Yanmin Hu; Jihua Tang

    2016-01-01

    Seed aging decreases the quality and vigor of crop seeds, thereby causing substantial agricultural and economic losses in crops. To identify genetic differences in seed aging between homozygotes and heterozygotes in maize, the seeds of a set of recombinant inbred lines (RILs) and an immortalized F2 (IF2) population were subjected to artificial aging treatments for 0, 2, 3, and 4 days under 45 ºC and 85%relative humidity and seed vigor was then evaluated in a field experiment. Seed vigor of all entries tested decreased sharply with longer aging treatment and seed vigor decreased more slowly in heterozygotes than in homozygotes. Forty-nine QTL were detected for four measured seed vigor traits in the RIL (28 QTL) and IF2 (21 QTL) populations. Only one QTL, qGP5, was detected in both populations, indicating that the genes involved in anti-aging mechanisms differed between inbred lines and hybrids. Several QTL were identified to be responsible for multiple seed vigor traits simultaneously in the RIL and IF2 populations under artificial aging conditions. These QTL may include major genes for seed vigor or seed aging. QTL qVI4b and qGE3a detected in the RIL population coincided with genes ZmLOX1 and ZmPLD1 in the same respective chromosomal regions. These QTL would be useful for screening for anti-aging genes in maize breeding.

  11. A contemplation in negation and emphasizes of outstanding philosophers of Tehran philosophy school in immortality of subject in substantial movement.

    Directory of Open Access Journals (Sweden)

    mohamad khosravi farsani

    2015-03-01

    Full Text Available Agha Ali and Jelveh ,two of outstanding of Tehran philosophy school, have reconsidered Sandra's opinions in two opposite sides. Agha Ali is the claimant of negation and ambiguity in most of Sandra's opinions while emphasizing on transcendent theosophy foundations ,and he tries to make these ambiguities clear .However , Jelveh follows Avicenna's way and has the idea of criticizing Sandra .This article has chosen the problem Of immortality of subject in substantial movement between all debates of these two philosophers of the same age.in this essay we are going to survey Agha Ali's claims in his new explantation in one hand ,and survey and criticize the new explanation of Jelveh in negation Of substantial movement .One of the consequences of surveying and criticizing these two philosophers is that we recognize Agha Ali has succeeded in making Sadra's opinions clear by presenting a new explanation of substantial movement subject. However ,Jelveh has merged Sadra's opinions with Avicenna's instead of debilitating Sadra's opinions and stabilizing Avicenna's opinions.

  12. Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yi; Pirisi, Lucia [Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC (United States); Creek, Kim E., E-mail: creekk@sccp.sc.edu [Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC (United States)

    2013-09-15

    We compared the levels of the Ski oncoprotein, an inhibitor of transforming growth factor-beta (TGF-β) signaling, in normal human keratinocytes (HKc), HPV16 immortalized HKc (HKc/HPV16), and differentiation resistant HKc/HPV16 (HKc/DR) in the absence and presence of TGF-β. Steady-state Ski protein levels increased in HKc/HPV16 and even further in HKc/DR, compared to HKc. TGF-β treatment of HKc, HKc/HPV16, and HKc/DR dramatically decreased Ski. TGF-β-induced Ski degradation was delayed in HKc/DR. Ski and phospho-Ski protein levels are cell cycle dependent with maximal Ski expression and localization to centrosomes and mitotic spindles during G2/M. ShRNA knock down of Ski in HKc/DR inhibited cell proliferation. More intense nuclear and cytoplasmic Ski staining and altered Ski localization were found in cervical cancer samples compared to adjacent normal tissue in a cervical cancer tissue array. Overall, these studies demonstrate altered Ski protein levels, degradation and localization in HPV16-transformed human keratinocytes and in cervical cancer. - Highlights: • Ski oncoprotein levels increase during progression of HPV16-transformed cells. • Ski and phospho-Ski protein levels are cell cycle dependent. • Ski knock-down in HPV16-transformed keratinocytes inhibited cell proliferation. • Cervical cancer samples overexpress Ski.

  13. Conophylline Promotes the Proliferation of Immortalized Mesenchymal Stem Cells Derived from Fetal Porcine Pancreas (iPMSCs)

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hui-ru; HUA Jin-lian; LI Dan; CAO Hui; L Xiao; CHU Yuan-kui; BAI Yao-fu; JIN Ya-ping; PENG Sha; DOU Zhong-ying

    2013-01-01

    Conophylline, is a bis (indole) alkaloid consisting of two pentacyclic aspidosperma skeletons, isolated from Tabernaemontana divaricata, which has been found to induce b-cell differentiation in rat pancreatic acinar carcinoma cells and in cultured rat pancreatic tissue. However, the precise role of conophylline in the growth and survival of immortalized pancreatic mesenchymal stem cells (iPMSCs) derived from fetal porcine pancreas were not understood at present. To determine whether this molecule is involved in controlling the proliferation of iPMSCs, we examined the effects of conophylline on iPMSCs. We found that conophylline can robustly stimulate iPMSCs proliferation, even promote their potential differentiation into islet-like clusters analyzed by cell counting, morphology, RT-PCR and real-time PCR, Western blotting, glucose-stimulated insulin release and insulin content analysis. The effects of conophylline were inhibited by LY294002, which is the inhibitor of the PI3K pathway. These results suggest that conophylline plays a key role in the regulation of cell mass proliferation, maintenance of the undifferentiated state of iPMSCs and also promotes iPMSCs differentiated into insulin-producing cells.

  14. Alte Psychoanalytiker/-innen

    OpenAIRE

    Ullrich, Peter

    2011-01-01

    Die Arbeit untersucht Berufstätigkeit und Berufsausstieg alter Psychoanalytiker/-innen. Dazu werden der konzeptuelle Forschungsstand zum Thema referiert, zu dem es bisher fast keine empirische Forschung gab, und eigene Ergebnisse aus zwei Befragungen (eine standardisierte Fragebogenerhebung und eine Studie auf Basis berufsbiographischer narrativer Interviews) vorgestellt. Diese geben Auskunft über die hohe Erwerbsneigung der untersuchten Gruppe vor dem 1.1.1937 geborener Analytiker/-innen (69...

  15. Alt koster 10 kr

    DEFF Research Database (Denmark)

    Ejersbo, Lisser Rye

    2014-01-01

    Jeg havde engang en elev, som fortalte, at når han gik i byen for at købe ind, så var det nemt at beregne, om han havde nok penge med i byen. Han sagde bare, at alle varerne kun kostede 10 kr. Det kan lyde som lidt af en tilsnigelse, så klassen og jeg besluttede at undersøge om hans metode virkede....

  16. Resonance energy transfer from quinolinone modified polystyrene-block-poly(styrene-alt-maleic anhydride) copolymer to terbium(III) metal ions

    Energy Technology Data Exchange (ETDEWEB)

    Výprachtický, Drahomír, E-mail: vyprachticky@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovský Sq. 2, 162 06 Prague 6 (Czech Republic); Mikeš, František [New York University Polytechnic School of Engineering, Polymer Research Institute, 6 MetroTech Center, Brooklyn, NY 11201 (United States); Lokaj, Jan; Pokorná, Veronika; Cimrová, Věra [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovský Sq. 2, 162 06 Prague 6 (Czech Republic)

    2015-04-15

    Polystyrene-block-poly(styrene-alt-maleic anhydride) was synthesized by nitroxide mediated radical polymerization and modified with 7-amino-4-methylquinolin-2(1H)-one (I) and methanol. The formed block polymer ligand contained a quinolinone fluorophore (Ω) and carboxyl (III) or sodium carboxylate (IV) binding sites. The ligand-to-metal resonance energy transfer (RET) and ligand binding properties of [III–Tb{sup 3+}] and [IV–Tb{sup 3+}] complexes were investigated by steady-state and time-resolved luminescence spectroscopy in tetrahydrofuran/methanol and/or tetrahydrofuran/deuterated methanol mixtures and compared with those of a low-molecular-weight model ligand, i.e. the sodium salt of N-(4-methyl-2-oxo-1,2-dihydroquinolin-7-yl)succinamic acid (II). The long-lived emission intensities of Tb{sup 3+} at 490, 545, 585, and 620 nm corresponding to the {sup 5}D{sub 4}→{sup 7}F{sub 6}, {sup 5}D{sub 4}→{sup 7}F{sub 5}, {sup 5}D{sub 4}→{sup 7}F{sub 4}, and {sup 5}D{sub 4}→{sup 7}F{sub 3} transitions, respectively, were strongly increased by the addition of ligands in the order [II-Tb{sup 3+}]⪡[III-Tb{sup 3+}]<[IV-Tb{sup 3+}]. The efficiency of energy transfer (E) was evaluated from the emission intensity of the donor (Ω) in the presence or absence of the acceptor (Tb{sup 3+}) depending on the acceptor concentration and ligand neutralization. It was concluded that the macromolecular ligand structural properties (polymer coil and supramolecular structures, e.g. micelles) were responsible for the increase in RET. The time-resolved luminescence measurements revealed that the binding affinity of the ligands II, III, and IV increased in the order II

  17. Comparative Cytotoxicity of Glycyrrhiza glabra Roots from Different Geographical Origins Against Immortal Human Keratinocyte (HaCaT), Lung Adenocarcinoma (A549) and Liver Carcinoma (HepG2) Cells.

    Science.gov (United States)

    Basar, Norazah; Oridupa, Olayinka Ayotunde; Ritchie, Kenneth J; Nahar, Lutfun; Osman, Nashwa Mostafa M; Stafford, Angela; Kushiev, Habibjon; Kan, Asuman; Sarker, Satyajit D

    2015-06-01

    Glycyrrhiza glabra L. (Fabaceae), commonly known as 'liquorice', is a well-known medicinal plant. Roots of this plant have long been used as a sweetening and flavouring agent in food and pharmaceutical products, and also as a traditional remedy for cough, upper and lower respiratory ailments, kidney stones, hepatitis C, skin disorder, cardiovascular diseases, diabetes, gastrointestinal ulcers and stomach ache. Previous pharmacological and clinical studies have revealed its antitussive, antiinflammatory, antiviral, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and cardioprotective properties. While glycyrrhizin, a sweet-tasting triterpene saponin, is the principal bioactive compound, several bioactive flavonoids and isoflavonoids are also present in the roots of this plant. In the present study, the cytotoxicity of the methanol extracts of nine samples of the roots of G. glabra, collected from various geographical origins, was assessed against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cell lines using the in vitro 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide cell toxicity/viability assay. Considerable variations in levels of cytotoxicity were observed among various samples of G. glabra.

  18. Performance of an Optimized Paper-Based Test for Rapid Visual Measurement of Alanine Aminotransferase (ALT in Fingerstick and Venipuncture Samples.

    Directory of Open Access Journals (Sweden)

    Sidhartha Jain

    Full Text Available A paper-based, multiplexed, microfluidic assay has been developed to visually measure alanine aminotransferase (ALT in a fingerstick sample, generating rapid, semi-quantitative results. Prior studies indicated a need for improved accuracy; the device was subsequently optimized using an FDA-approved automated platform (Abaxis Piccolo Xpress as a comparator. Here, we evaluated the performance of the optimized paper test for measurement of ALT in fingerstick blood and serum, as compared to Abaxis and Roche/Hitachi platforms. To evaluate feasibility of remote results interpretation, we also compared reading cell phone camera images of completed tests to reading the device in real time.96 ambulatory patients with varied baseline ALT concentration underwent fingerstick testing using the paper device; cell phone images of completed devices were taken and texted to a blinded off-site reader. Venipuncture serum was obtained from 93/96 participants for routine clinical testing (Roche/Hitachi; subsequently, 88/93 serum samples were captured and applied to paper and Abaxis platforms. Paper test and reference standard results were compared by Bland-Altman analysis.For serum, there was excellent agreement between paper test and Abaxis results, with negligible bias (+4.5 U/L. Abaxis results were systematically 8.6% lower than Roche/Hitachi results. ALT values in fingerstick samples tested on paper were systematically lower than values in paired serum tested on paper (bias -23.6 U/L or Abaxis (bias -18.4 U/L; a correction factor was developed for the paper device to match fingerstick blood to serum. Visual reads of cell phone images closely matched reads made in real time (bias +5.5 U/L.The paper ALT test is highly accurate for serum testing, matching the reference method against which it was optimized better than the reference methods matched each other. A systematic difference exists between ALT values in fingerstick and paired serum samples, and can be

  19. 抗-HCV和HCV-RNA检测及其与ALT的相关性分析%Quantitative analysis of serum anti-HCV, HCV-RNA and ALT

    Institute of Scientific and Technical Information of China (English)

    贾珉; 邵芳

    2012-01-01

    目的 探讨化学免疫发光法(CLIA)定量检测抗-HCV和FQ-PCR法检测HCV-RNA含量与丙氨酸氨基转移酶(ALT)水平的相关性.方法 用CLIA定量筛选抗-HCV阳性的100例病人标本,以荧光定量PCR法检测HCV-RNA含量和酶速率法检测ALT浓度水平,并对所得数据进行统计分析.结果 在100份抗-HCV阳性标本中,检出HCV-RNA阳性者76例,阳性率为76%.随着抗-HCV的S/CO值增高,HCV-RNA检出率增高较明显;ALT水平与HCV-RNA含量无显著相关性(P>0.05),但ALT异常率与HCV-RNA含量呈正相关.结论 在HCV诊断与疗效观察中,血清抗HCV、HCV-RNA和ALT指标各有利弊,3者有机结合能正确诊断和预测肝脏损伤及评价疗效.%Objective To analyze the correlation among the quantitative detection of serum anti-HCV by chemiluminescene immunoassay(CLIA), the content of HCV-RNA and alanine aminotransferase (ALT) levels. Methods The sera from 100 patients with CLIA positive results were used in this study. The level of serum HCV-RNA and ALT was detected by real-lime fluorescent quantitative assay (FQ-PCR) and enzyme-rate method, respectively. The data were analyzed by statistical method. Results 76 patients were found HCV-RNA positive, with a positive rate of 76%. The HCV-RNA positive rate was positively correlated with the anti-HCV S/CO result. There was no correlation between the level of ALT and the content of HCV-RNA (P>0.05), but the content of HCV-RNA was correlated with the ALT. Conclusion The level of anti-HCV antibody,HCV-RNA and ALT should all be used in the diagnosis of HCV. An appropriate combination of these indexes has important clinical significance in the diagnosis, prediction of liver injury and early treatment.

  20. Revealing Rembrandt

    Directory of Open Access Journals (Sweden)

    Andrew J Parker

    2014-04-01

    Full Text Available The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI. Our results emphasised the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt’s portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings.

  1. Altı eksenli robot kolun hareketsel karakteristliğinin görsel programlanması ve gerçek zamanlı uygulamalar

    OpenAIRE

    Güzel, Mehmet Serdar

    2008-01-01

    Bu Tez çalışması kapsamında Beş ve Altı Eksenli Robot kolların matematiksel analizinin yapılması, görsel tabanlı yazılımlar geliştirerek; Robot kolların yönetilmesi ve gerçek zamanlı akıllı uygulamalarda kullanılması hedeflenmiştir. Uygulama ve Teorik kısımları için robot kol modeli olarak Lynx şirketinin Beş Serbestlik Derecesine sahip (5 DOF) Altı eklemli robot kolu kullanıldı. Matematik analiz kapsamında robot kolun hareket karakteristiği incelenmiştir. Bu analiz, Robot ko...

  2. Investigation of magnetic properties and electronic structure of layered-structure borides AlT2B2 (T=Fe, Mn, Cr) and AlFe2–xMnxB2

    International Nuclear Information System (INIS)

    The ternary phases AlT2B2 (T=Fe, Mn, Cr) and quaternary phases AlFe2–xMnxB2 have been synthesized by arc-melting and characterized by powder X-ray diffraction, magnetic measurements, Mössbauer spectroscopy, and electronic band structure calculations. All the compounds adopt the AlFe2B2-type structure, in which infinite zigzag chains of B atoms are connected by Fe atoms into [Fe2B2] slabs that alternate with layers of Al atoms along the b axis. The magnetic measurements reveal that AlFe2B2 is a ferromagnet with TC=282 K while AlMn2B2 and AlCr2B2 do not show magnetic ordering in the studied temperature range of 1.8–400 K. A systematic investigation of solid solutions AlFe2−xMnxB2 showed a non-linear change in the structural and magnetic behavior. The ferromagnetic ordering temperature is gradually decreased as the Mn content (x) increases. The Mössbauer spectra reveal the presence of non-magnetic (NM) and ferromagnetic (FM) spectral components in all Mn-containing samples, with the amount of NM fraction increasing as the Mn content increases. While for the AlFe2−xMnxB2 samples with x=0.0 and 0.4 the hyperfine splitting of the FM spectral component collapses at temperatures close to the Curie temperatures determined from the magnetic measurements, for the x=1.2 and 1.6 samples the FM fraction exhibits a sizable unquenched hyperfine splitting at room temperature, a finding that is inconsistent with the observed magnetic properties. Along with the increase in the amount of the NM fraction, this observation suggests formation of Fe-rich and Mn-rich regions in the structure of the solid solutions. Quantum-chemical calculations and crystal orbital Hamilton population analysis provide a clear explanation of the distinction in properties for this series of compounds and also reveal the importance of electronic factors in modifying the magnetic properties of these materials. - Graphical abstract: We follow a gradual evolution of magnetic properties in a series of

  3. Effect of Nanosilver Particles on Alanin Amino Transferase (ALT) Activity and White Blood Cells (WBC) Level in Male Wistar Rats, In Vivo Condition

    OpenAIRE

    Nooshin Naghsh; Ali Noori; Heydar Aqababa; Samira Amirkhani-Dehkordi

    2012-01-01

    Background: Nanosilver is extensively used in medical equipment. Given the importance of white blood cells (WBC) in the immune system and liver cells in the body detoxification, this study has examined the effects of nanosilver particles on the white cell count and ALT liver enzyme in male Wistar rats. Materials and Methods: This experimental study was conducted on 40 adult male Wistar rats, provided from Pasteur Institute of Tehran. Nanosilver particles with concentrations of 50, 100, 200 an...

  4. Pentosan polysulfate regulates scavenger receptor-mediated, but not fluid-phase, endocytosis in immortalized cerebral endothelial cells.

    Science.gov (United States)

    Deli, M A; Abrahám, C S; Takahata, H; Katamine, S; Niwa, M

    2000-12-01

    1. Effects of pentosan polysulfate (PPS) and the structurally related sulfated polyanions dextran sulfate, fucoidan, and heparin on the scavenger receptor-mediated and fluidphase endocytosis in GP8 immortalized rat brain endothelial cells were investigated. 2. Using 1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarboxyamine perchlorate-labeled acetylated low-density lipoprotein (DiI-AcLDL), we found a binding site with high affinity and low binding capacity, and another one with low affinity and high binding capacity. Increasing ligand concentrations could not saturate DiI-AcLDL uptake. DiI-AcLDL uptake, but not binding, was sensitive to pretreatment with filipin, an inhibitor of caveola formation. 3. PPS (20-200 microg/ml) significantly reduced the binding of DiI-AcLDL after coincubation for 3 hr, though this effect was less expressed after 18 hr. Among other polyanions, only fucoidan decreased the DiI-AcLDL binding after 3 hr, whereas dextran sulfate significantly increased it after 18 hr. PPS treatment induced an increase in DiI-AcLDL uptake, whereas other polysulfated compounds caused a significant reduction. 4. Fluid-phase endocytosis determined by the accumulation of Lucifer yellow was concentration and time dependent in GP8 cells. Coincubation with PPS or other sulfated polyanions could not significantly alter the rate of Lucifer yellow uptake. 5. In conclusion. PPS decreased the binding and increased the uptake of DiI-AcLDL in cerebral endothelial cells, an effect not mimicked by the other polyanions investigated.

  5. Telomerase-immortalized non-malignant human prostate epithelial cells retain the properties of multipotent stem cells

    International Nuclear Information System (INIS)

    Understanding prostate stem cells may provide insight into the origin of prostate cancer. Primary cells have been cultured from human prostate tissue but they usually survive only 15-20 population doublings before undergoing senescence. We report here that RC-170N/h/clone 7 cells, a clonal cell line from hTERT-immortalized primary non-malignant tissue-derived human prostate epithelial cell line (RC170N/h), retain multipotent stem cell properties. The RC-170N/h/clone 7 cells expressed a human embryonic stem cell marker, Oct-4, and potential prostate epithelial stem cell markers, CD133, integrin α2β1hi and CD44. The RC-170N/h/clone 7 cells proliferated in KGM and Dulbecco's Modified Eagle Medium with 10% fetal bovine serum and 5 μg/ml insulin (DMEM + 10% FBS + Ins.) medium, and differentiated into epithelial stem cells that expressed epithelial cell markers, including CK5/14, CD44, p63 and cytokeratin 18 (CK18); as well as the mesenchymal cell markers, vimentin, desmin; the neuron and neuroendocrine cell marker, chromogranin A. Furthermore the RC170 N/h/clone 7 cells differentiated into multi tissues when transplanted into the sub-renal capsule and subcutaneously of NOD-SCID mice. The results indicate that RC170N/h/clone 7 cells retain the properties of multipotent stem cells and will be useful as a novel cell model for studying the mechanisms of human prostate stem cell differentiation and transformation

  6. Shutoff of BZLF1 gene expression is necessary for immortalization of primary B cells by Epstein-Barr virus.

    Science.gov (United States)

    Yu, Xianming; McCarthy, Patrick J; Wang, Zhenxun; Gorlen, Daniel A; Mertz, Janet E

    2012-08-01

    The BZLF1 gene controls the switch between latent and lytic infection by Epstein-Barr virus (EBV). We previously reported that both the ZV and ZIIR elements within the BZLF1 promoter, Zp, are potent transcription silencers within the context of an intact EBV genome. We report here identification of another sequence element, ZV', which synergized with ZV in repressing Zp via binding ZEB1 or ZEB2. We then determined the phenotype of a variant of EBV strain B95.8 in which the ZV, ZV', and ZIIR elements were concurrently mutated. HEK293 cell lines infected with this triple mutant (tmt) virus spontaneously synthesized 6- to 10-fold more viral BZLF1, BRLF1, BMRF1, and BLLF1 RNAs, 3- to 6-fold more viral Zta, Rta, and EAD proteins, 3- to 5-fold more viral DNA, and 7- to 9-fold more infectious virus than did 293 cell lines latently infected with either the ZV ZV' double mutant (dmt) or ZIIR mutant (mt) virus. While ZV ZV' ZIIR tmt EBV efficiently infected human primary blood B cells in vitro, it was highly defective in immortalizing them. Instead of the nearly complete silencing of BZLF1 gene expression that occurs within 4 days after primary infection with wild-type EBV, the ZV ZV' ZIIR tmt-infected cells continued to synthesize BZLF1 RNA, with 90% of them dying within 9 days postinfection. BL41 cells infected with this "superlytic" virus also exhibited increased synthesis of BZLF1 and BMRF1 RNAs. Thus, we conclude that the ZV, ZV', and ZIIR silencing elements act synergistically to repress transcription from Zp, thereby tightly controlling BZLF1 gene expression, which is crucial for establishing and maintaining EBV latency.

  7. Establishment of c-myc-immortalized Kupffer cell line from a C57BL/6 mouse strain

    Directory of Open Access Journals (Sweden)

    Hiroshi Kitani

    2014-01-01

    Full Text Available We recently demonstrated in several mammalian species, a novel procedure to obtain liver-macrophages (Kupffer cells in sufficient numbers and purity using a mixed primary culture of hepatocytes. In this study, we applied this method to the C57BL/6 mouse liver and established an immortalized Kupffer cell line from this mouse strain. The hepatocytes from the C57BL/6 adult mouse liver were isolated by a two-step collagenase perfusion method and cultured in T25 culture flasks. Similar to our previous studies, the mouse hepatocytes progressively changed their morphology into a fibroblastic appearance after a few days of culture. After 7–10 days of culture, Kupffer-like cells, which were contaminants in the hepatocyte fraction at the start of the culture, actively proliferated on the mixed fibroblastic cell sheet. At this stage, a retroviral vector containing the human c-myc oncogene and neomycin resistance gene was introduced into the mixed culture. Gentle shaking of the culture flask, followed by the transfer and brief incubation of the culture supernatant, resulted in a quick and selective adhesion of Kupffer cells to a plastic dish surface. After selection with G418 and cloning by limiting dilutions, a clonal cell line (KUP5 was established. KUP5 cells displayed typical macrophage morphology and were stably passaged at 4–5 days intervals for more than 5 months, with a population doubling time of 19 h. KUP5 cells are immunocytochemically positive for mouse macrophage markers, such as Mac-1, F4/80. KUP5 cells exhibited substantial phagocytosis of polystyrene microbeads and the release of inflammatory cytokines upon lipopolysaccharide stimulation. Taken together, KUP5 cells provide a useful means to study the function of Kupffer cells in vitro.

  8. Brucella suis vaccine strain S2-infected immortalized caprine endometrial epithelial cell lines induce non-apoptotic ER-stress.

    Science.gov (United States)

    Wang, Xiangguo; Lin, Pengfei; Yin, Yanlong; Zhou, Jinhua; Lei, Lanjie; Zhou, Xudong; Jin, Yaping; Wang, Aihua

    2015-05-01

    Brucella, which is regarded as an intracellular pathogen responsible for a zoonotic disease called brucellosis, survives and proliferates within several types of phagocytic and non-phagocytic cells. Brucella infects not only their preferred hosts but also other domestic and wild animal species, inducing abortion and infertility. Therefore, the interaction between uterine cells and Brucella is important for understanding the pathogenesis of this disease. In this study, we describe the Brucella suis vaccine strain S2 (B.suis.S2) infection and replication in the immortalized caprine endometrial epithelial cell line hTERT-EECs and the induced cellular and molecular response modulation in vitro. We found that B.suis S2 was able to infect and replicate to high titers and inhibit the proliferation of EECs and induce non-apoptotic pathways, as determined by B.suis.S2 detection using MTT and acridine orange/ethidium bromide (AO/EB) staining and flow cytometry. We explored the evidence of non-apoptotic pathways using real-time quantitative RT-PCR and by western blot analysis. Finally, we discovered the over-expression of GRP78, ATF4, ATF6, PERK, eIF2α, CHOP, and cytochrome c (Cyt-c) but not IRE1, xbp-1, and caspase-3 in B.suis.S2 (HK)-attacked and B.suis.S2-infected cells, suggesting that the molecular mechanism of ER stress sensor activation by B.suis.S2 is basically concomitant with that by B.suis.S2 (HK) and that ER stress, especially the PERK pathway, plays an important role in the process of B.suis.S2 infecting EEC, which may, in part, explain the role of the uterus in the pathogenesis of B.suis.S2. PMID:25633898

  9. Retroviral insertional mutagenesis in telomerase-immortalized hepatocytes identifies RIPK4 as novel tumor suppressor in human hepatocarcinogenesis.

    Science.gov (United States)

    Heim, D; Cornils, K; Schulze, K; Fehse, B; Lohse, A W; Brümmendorf, T H; Wege, H

    2015-01-15

    Carcinogenesis is a multistep process involving alterations in various cellular pathways. The critical genetic events driving the evolution of primary liver cancer, specifically hepatoblastoma and hepatocellular carcinoma (HCC), are still poorly understood. However, telomere stabilization is acknowledged as prerequisite for cancer progression in humans. In this project, human fetal hepatocytes were utilized as a cell culture model for untransformed, proliferating human liver cells, with telomerase activation as first oncogenic hit. To elucidate critical downstream genetic events driving further transformation of immortalized liver cells, we used retroviral insertional mutagenesis as an unbiased approach to induce genetic alterations. Following isolation of hyperproliferating, provirus-bearing cell clones, we monitored cancer-associated growth properties and characterized changes toward a malignant phenotype. Three transformed clones with the ability to form colonies in soft agar were expanded. As proof-of-principle for our experimental setup, we identified a transforming insertion on chromosome 8 within the pleiomorphic adenoma gene 1 (PLAG1), resulting in a 20-fold increase in PLAG1 expression. Upregulation of PLAG1 has already been described to promote human hepatoblastoma development. In a separate clone, a transforming insertion was detected in close proximity to the receptor-interacting serine-threonine kinase 4 (RIPK4) with an approximately eightfold suppression in RIPK4 expression. As validation for this currently unknown driver in hepatocarcinogenesis, we examined RIPK4 expression in human HCC samples and confirmed a significant suppression of RIPK4 in 80% of the samples. Furthermore, overexpression of RIPK4 in transformed human fetal hepatocytes resulted in an almost complete elimination of anchorage-independent growth. On the basis of these data, we propose RIPK4 as a novel putative tumor suppressor in human hepatocarcinogenesis. PMID:24413083

  10. Evaluation of CO2-philicity of poly(vinyl acetate) and poly(vinyl acetate-alt-maleate) copolymers through molecular modeling and dissolution behavior measurement.

    Science.gov (United States)

    Hu, Dongdong; Sun, Shaojun; Yuan, Peiqing; Zhao, Ling; Liu, Tao

    2015-02-19

    Multiscale molecular modeling and dissolution behavior measurement were both used to evaluate the factors conclusive on the CO2-philicity of poly(vinyl acetate) (PVAc) homopolymer and poly(vinyl acetate-alt-maleate) copolymers. The ab initio calculated interaction energies of the candidate CO2-philic molecule models with CO2, including vinyl acetate dimer (VAc), dimethyl maleate (DMM), diethyl maleate (DEM), and dibutyl maleate (DBM), showed that VAc was the most CO2-philc segment. However, the cohesive energy density, solubility parameter, Flory-Huggins parameter, and radial distribution functions calculated by using the molecular dynamics simulations for the four polymer and polymer-CO2 systems indicated that poly(VAc-alt-DBM) had the most CO2-philicity. The corresponding polymers were synthesized by using free radical polymerization. The measurement of cloud point pressures of the four polymers in CO2 also demonstrated that poly(VAc-alt-DBM) had the most CO2-philicity. Although copolymerization of maleate, such as DEM or DBM, with PVAc reduced the polymer-CO2 interactions, the weakened polymer-polymer interaction increased the CO2-philicity of the copolymers. The polymer-polymer interaction had a significant influence on the CO2-philicity of the polymer. Reduction of the polymer-polymer interaction might be a promising strategy to prepare the high CO2-philic polymers on the premise that the strong polymer-CO2 interaction could be maintained.

  11. Fibroscan Compared to FIB-4, APRI, and AST/ALT Ratio for Assessment of Liver Fibrosis in Saudi Patients With Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Fallatah, Hind I.; Akbar, Hisham O.; Fallatah, Alyaa M.

    2016-01-01

    Background Nonalcoholic fatty liver disease (NAFLD) is being increasingly recognized as a cause of chronic liver disease. It has also been associated with devastating outcomes such as decompensated liver cirrhosis and hepatocellular carcinoma, as well as diabetes and metabolic syndrome. Objectives This study was conducted in order to assess liver fibrosis using Fibroscan, and to compare these results to the use of Fibrosis-4 (FIB-4) scores, AST platelet ratio index (APRI scores), and the AST/ALT ratios on NAFLD patients. Patients and Methods A cross sectional study was conducted on NAFLD patients who underwent Fibroscan examinations between September 1, 2011 and June 30, 2014. Demographic data was collected, including sex, age, and nationality; serum alanine aminotransferase levels (ALT, 30 - 65 U/L), serum aspartate aminotransferase levels (AST, 15 - 37 U/L), and platelet counts (150 - 400 k/μL) were also determined. The stages of fibrosis (F0 1 - 6, F1 6.1 - 7, F2 7 - 9, F3 9.1 - 10.3, and F4 ≥ 10.4) were defined in kPa. For each patient, the AST/ALT ratio was also measured. The results of APRI and FIB-4 were compared with the Fibroscan fibrosis scores. Results The results of 122 patients were analyzed, including 65 (53.3%) males with a mean age of 50.2 years (SD: 13.7; range: 18 - 86). The males were significantly younger than the females (48.7 years (SD: 16.03) versus 51.8 years (SD: 10.3 P = 0.05), respectively). The mean stiffness score was 12.02 (SD: 12.7) kPa. Forty-four patients (36%) had advanced fibrosis. The mean platelet and serum ALT levels were normal. There was a significant positive correlation between the Fibroscan results and the AST/ALT ratios, the APRI scores, and the FIB-4 results. Similarly, there was a significant positive correlation between age and fibrosis score, and a significant negative correlation between platelet count and stiffness score. Conclusions The data showed that more than one-third of the cohort exhibited advanced

  12. Establishment of Immortalized Mouse Bmp2 Knock-Out Dental Papilla Mesenchymal Cells Necessary for Study of Odontoblastic Differentiation and Odontogenesis

    Science.gov (United States)

    Wu, Lian; Wang, Feng; Donly, Kevin J.; Wan, Chunyan; Luo, Daoshu; Harris, Stephen E.; Macdougall, Mary; Chen, Shuo

    2016-01-01

    Bmp2 is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta, showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain lot of primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis. In this study, our goal was to generate an immortalized deleted Bmp2 dental papilla mesenchymal (iBmp2ko/ko dp) cell line by introducing Cre fluorescent protein (GFP) into the immortalized mouse floxed Bmp2 dental papilla mesenchymal (iBmp2fx/fx dp) cells. iBmp2ko/ko dp cells were confirmed by GFP and PCR. The deleted Bmp2 cells exhibited slow cell proliferation rate and cell growth was arrested in G2 phase. Expression of tooth-related marker genes and cell differentiation were decreased in the deleted cells. Importantly, extracellular matrix remodeling was impaired in the iBmp2ko/ko dp cells as reflected by the decreased Mmp-9 expression. In addition, with exogenous Bmp2 induction, these cell differentiation and mineralization were rescued as well as extracellular matrix remodeling was enhanced. Therefore, we for the first time described establishment of iBmpko/ko cells that are useful for study of mechanisms in regulating dental papilla mesenchymal cell lineages. PMID:26037045

  13. Chromosomal instability in human mesenchymal stem cells immortalized with human papilloma virus E6, E7, and hTERT genes.

    Science.gov (United States)

    Takeuchi, Masao; Takeuchi, Kikuko; Kohara, Arihiro; Satoh, Motonobu; Shioda, Setsuko; Ozawa, Yutaka; Ohtani, Azusa; Morita, Keiko; Hirano, Takashi; Terai, Masanori; Umezawa, Akihiro; Mizusawa, Hiroshi

    2007-01-01

    Human mesenchymal stem cells (hMSCs) are expected to be an enormous potential source for future cell therapy, because of their self-renewing divisions and also because of their multiple-lineage differentiation. The finite lifespan of these cells, however, is a hurdle for clinical application. Recently, several hMSC lines have been established by immortalized human telomerase reverse transcriptase gene (hTERT) alone or with hTERT in combination with human papillomavirus type 16 E6/E7 genes (E6/E7) and human proto-oncogene, Bmi-1, but have not so much been characterized their karyotypic stability in detail during extended lifespan under in vitro conditions. In this report, the cells immortalized with the hTERT gene alone exhibited little change in karyotype, whereas the cells immortalized with E6/E7 plus hTERT genes or Bmi-1, E6 plus hTERT genes were unstable regarding chromosome numbers, which altered markedly during prolonged culture. Interestingly, one unique chromosomal alteration was the preferential loss of chromosome 13 in three cell lines, observed by fluorescence in situ hybridization (FISH) and comparative-genomic hybridization (CGH) analysis. The four cell lines all maintained the ability to differentiate into both osteogenic and adipogenic lineages, and two cell lines underwent neuroblastic differentiation. Thus, our results were able to provide a step forward toward fulfilling the need for a sufficient number of cells for new therapeutic applications, and substantiate that these cell lines are a useful model for understanding the mechanisms of chromosomal instability and differentiation of hMSCs. PMID:17514511

  14. Interaction of CtBP with adenovirus E1A suppresses immortalization of primary epithelial cells and enhances virus replication during productive infection

    Energy Technology Data Exchange (ETDEWEB)

    Subramanian, T.; Zhao, Ling-jun; Chinnadurai, G., E-mail: chinnag@slu.edu

    2013-09-01

    Adenovirus E1A induces cell proliferation, oncogenic transformation and promotes viral replication through interaction with p300/CBP, TRRAP/p400 multi-protein complex and the retinoblastoma (pRb) family proteins through distinct domains in the E1A N-terminal region. The C-terminal region of E1A suppresses E1A/Ras co-transformation and interacts with FOXK1/K2, DYRK1A/1B/HAN11 and CtBP1/2 (CtBP) protein complexes. To specifically dissect the role of CtBP interaction with E1A, we engineered a mutation (DL→AS) within the CtBP-binding motif, PLDLS, and investigated the effect of the mutation on immortalization and Ras cooperative transformation of primary cells and viral replication. Our results suggest that CtBP–E1A interaction suppresses immortalization and Ras co-operative transformation of primary rodent epithelial cells without significantly influencing the tumorigenic activities of transformed cells in immunodeficient and immunocompetent animals. During productive infection, CtBP–E1A interaction enhances viral replication in human cells. Between the two CtBP family proteins, CtBP2 appears to restrict viral replication more than CtBP1 in human cells. - Highlights: • Adenovirus E1A C-terminal region suppresses E1A/Ras co-transformation. • This E1A region binds with FOXK, DYRK1/HAN11 and CtBP cellular protein complexes. • We found that E1A–CtBP interaction suppresses immortalization and transformation. • The interaction enhances viral replication in human cells.

  15. Establishment of Immortalized Mouse Bmp2 Knock-Out Dental Papilla Mesenchymal Cells Necessary for Study of Odontoblastic Differentiation and Odontogenesis.

    Science.gov (United States)

    Wu, Lian; Wang, Feng; Donly, Kevin J; Wan, Chunyan; Luo, Daoshu; Harris, Stephen E; MacDougall, Mary; Chen, Shuo

    2015-11-01

    Bmp2 is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta, showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain lot of primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis. In this study, our goal was to generate an immortalized deleted Bmp2 dental papilla mesenchymal (iBmp2(ko/ko)dp) cell line by introducing Cre recombinase and green fluorescent protein (GFP) into the immortalized mouse floxed Bmp2 dental papilla mesenchymal (iBmp2(fx/fx)dp) cells. iBmp2(ko/ko)dp cells were confirmed by GFP and PCR. The deleted Bmp2 cells exhibited slow cell proliferation rate and cell growth was arrested in G2 phase. Expression of tooth-related marker genes and cell differentiation were decreased in the deleted cells. Importantly, extracellular matrix remodeling was impaired in the iBmp2(ko/ko)dp cells as reflected by the decreased Mmp-9 expression. In addition, with exogenous Bmp2 induction, these cell differentiation and mineralization were rescued as well as extracellular matrix remodeling was enhanced. Therefore, we for the first time described establishment of iBmp(ko/ko) cells that are useful for study of mechanisms in regulating dental papilla mesenchymal cell lineages. PMID:26037045

  16. Discussing the unqualified rate and analysing the upper limit of ALT donated by volunteers in Chongqing city%重庆市无偿献血者 ALT 正常值上限的分析与不合格率的探讨

    Institute of Scientific and Technical Information of China (English)

    程颖; 李维; 田耘博; 程燃

    2015-01-01

    Objective To investigate the upper limit of plasma′s alanine aminotransferase (ALT ) donated by volunteers in Chongqing city ,utmost avoid blood discarding due to ALT unqualified and provide a scientific basis for the improvement measures . Methods Checking 115 530 blood donors′ALT by rate method ,the activity of ALT value was normal distribution ,deem x ± 1 .96s as the upper limit of ALT of blood donors ,the upper limit of ALT and the unqualified rate was analyzed according tomonth ,age , gender .Results 95% upper limit of blood donors′ ALT reference range to less than 47 .88 U/L .From June to September ,ALT value unqualified rate compared with other months of the year have significant difference (P0 .05) .There was obvious difference about unqualified rate and upper limit between different sex group ,there was statistical significance (P<0 .05) .Conclusion The quantitative blood agen‐cies should increase propagandist strength ,optimize ALT screening strategy ,gender‐specific blood donors screening measures should be taken ,re‐establish a more scientific ALT Elimination standard ,the maximum reduct blood ALT′s failure rate .To ensure the safety and clinical local blood supply at the same time ,the maximum to avoid waste of blood .%目的:调查重庆市无偿献血者血浆丙氨酸氨基转移酶(ALT)的正常值上限,为最大限度的避免因ALT不合格而造成的血液报废提供科学依据和改进措施。方法用速率法检测115530名无偿献血者ALT,ALT活性值呈正态分布,采用x±1.96s作为正常值上限,对无偿献血者ALT正常上限值和不合格率按月份、年龄、性别进行统计分析。结果无偿献血者的ALT上限值95%的参考范围为不高于47.88U/L。6~9月ALT值的不合格率与其他月份比较差异有统计学意义(P<0.05);不同年龄间正常值上限和不合格率比较差异无统计学意义(P>0.05);不同性别间正常值上限和不合

  17. Mythological Novels as Biographies of Supernatural Beings and Cao Zhi’s Poetry about Immortals%仙传小说与曹植游仙诗

    Institute of Scientific and Technical Information of China (English)

    施健

    2013-01-01

    Cao Zhi was the first poet who writes poems about immortals .He wrote 11 such poems that can be found including Go up to the Sky (升天行) and Poem about Immortals (游仙诗), accounting for almost one -sixth of his creations.It is commonly thought that Cao Zhi’s poetry about immortals is affected by Qu Yuan ’s poem of Travel Faraway (远游).Meantime, the idea of supernatural beings of Taoism since the Han dynasty also im-pacts the formation of his creation.The descriptions of immortals in mythological novels in biography of supernatural beings and the complicated fairyland provide rich material for the creation of such poems .Their literariness is thus improved.%  曹植是游仙诗创作的第一人。他的游仙诗可考的大约有《升天行》《游仙诗》等11首,这几乎占了曹植诗歌创作总量的六分之一。目前学术界普遍认同曹植的游仙诗受到了屈原《远游》创作的影响,并且是结合了汉代以来的道教神仙思想而逐渐成型的。在道家思想领域,尤其是汉代以来的仙传小说对于大量神仙升天羽化故事的描写以及纷繁复杂的仙境的描绘给游仙诗这种诗歌的创作提供了大量的素材,文学性大大增强。曹植的游仙诗与仙传小说有着密切关系,两者互有促进,在文学史上有一定的影响。

  18. Expression of parathyroid hormone-related protein during immortalization of human peripheral blood mononuclear cells by HTLV-1: Implications for transformation

    Directory of Open Access Journals (Sweden)

    Nadella Kiran S

    2008-06-01

    Full Text Available Abstract Background Adult T-cell leukemia/lymphoma (ATLL is initiated by infection with human T-lymphotropic virus type-1 (HTLV-1; however, additional host factors are also required for T-cell transformation and development of ATLL. The HTLV-1 Tax protein plays an important role in the transformation of T-cells although the exact mechanisms remain unclear. Parathyroid hormone-related protein (PTHrP plays an important role in the pathogenesis of humoral hypercalcemia of malignancy (HHM that occurs in the majority of ATLL patients. However, PTHrP is also up-regulated in HTLV-1-carriers and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP patients without hypercalcemia, indicating that PTHrP is expressed before transformation of T-cells. The expression of PTHrP and the PTH/PTHrP receptor during immortalization or transformation of lymphocytes by HTLV-1 has not been investigated. Results We report that PTHrP was up-regulated during immortalization of lymphocytes from peripheral blood mononuclear cells by HTLV-1 infection in long-term co-culture assays. There was preferential utilization of the PTHrP-P2 promoter in the immortalized cells compared to the HTLV-1-transformed MT-2 cells. PTHrP expression did not correlate temporally with expression of HTLV-1 tax. HTLV-1 infection up-regulated the PTHrP receptor (PTH1R in lymphocytes indicating a potential autocrine role for PTHrP. Furthermore, co-transfection of HTLV-1 expression plasmids and PTHrP P2/P3-promoter luciferase reporter plasmids demonstrated that HTLV-1 up-regulated PTHrP expression only mildly, indicating that other cellular factors and/or events are required for the very high PTHrP expression observed in ATLL cells. We also report that macrophage inflammatory protein-1α (MIP-1α, a cellular gene known to play an important role in the pathogenesis of HHM in ATLL patients, was highly expressed during early HTLV-1 infection indicating that, unlike PTHrP, its expression was

  19. «El inmortal» de Jorge Luis Borges: el yo, infinitos, absolutos y vocabularios finales Jorge Luis Borges's «The Immortal»: the Self, Infinites, Absolutes, and Final Vocabularies

    Directory of Open Access Journals (Sweden)

    Jorge Sagastume

    2011-07-01

    ilosofía de la lengua.Jorge Luis Borges often consulted Mathematics and Imagination by E. Kasner and J. Newman, where they address the set theory (branch of mathematics that studies the relationship between sets proposed by Georg Cantor (18451918, and in which transfinite arithmetic (beyond finite arithmetic is established, and an epistemic system created to represent different levels of the ininite. Thus, Cantor labels the different levels of the ininite by assigning to each the irst letter of the Hebrew alphabet, the Aleph, followed by a number, depending on the level of infinite he is referring to (Aleph-zero, Aleph-one, etc.. Following these ideas, Borges weaves several narratives, discussing the ininite and the absolute. An example of such narratives is the collection of stories compiled under the title The Aleph, which opens with «The Immortal» and closes with the story that gives the collection its title. The objective of this paper is to study «The Immortal» under the Cantorian lens, so as to discuss one particular absolute, the self, and to suggest that it is impossible to establish a inal vocabulary, or a deinite deinition, about this topic. This impossibility, Borges proposes, is in part due to the apparent initude of language, on the one hand, and on the other, the fallible attributes of human memory are also crucial when it comes to deining anything. However, being the ironist Borges is, he is capable of providing through «The Immortal» a re-description of these issues by means of a transinite language that resolves some paradoxes while at the same time reveals others. Due to this way of writing, I propose Borges fosters a continuation of the dialogue among different disciplines. Though I will center my analysis on «The Immortal», to develop these ideas I will also revisit other stories in The Aleph departing from a theoretical approach rooted in the philosophy of language.

  20. Single-cell lineage tracking analysis reveals that an established cell line comprises putative cancer stem cells and their heterogeneous progeny

    Science.gov (United States)

    Sato, Sachiko; Rancourt, Ann; Sato, Yukiko; Satoh, Masahiko S.

    2016-01-01

    Mammalian cell culture has been used in many biological studies on the assumption that a cell line comprises putatively homogeneous clonal cells, thereby sharing similar phenotypic features. This fundamental assumption has not yet been fully tested; therefore, we developed a method for the chronological analysis of individual HeLa cells. The analysis was performed by live cell imaging, tracking of every single cell recorded on imaging videos, and determining the fates of individual cells. We found that cell fate varied significantly, indicating that, in contrast to the assumption, the HeLa cell line is composed of highly heterogeneous cells. Furthermore, our results reveal that only a limited number of cells are immortal and renew themselves, giving rise to the remaining cells. These cells have reduced reproductive ability, creating a functionally heterogeneous cell population. Hence, the HeLa cell line is maintained by the limited number of immortal cells, which could be putative cancer stem cells. PMID:27003384

  1. Bioethics in popular science: evaluating the media impact of The Immortal Llife of Henrietta Lacks on the biobank debate

    Science.gov (United States)

    2013-01-01

    Background The global expansion of biobanks has led to a range of bioethical concerns related to consent, privacy, control, ownership, and disclosure. As an opportunity to engage broader audiences on these concerns, bioethicists have welcomed the commercial success of Rebecca Skloot’s 2010 bestselling book The Immortal Life of Henrietta Lacks. To assess the impact of the book on discussion within the media and popular culture more generally, we systematically analyzed the ethics-related themes emphasized in reviews and articles about the book, and in interviews and profiles of Skloot. Methods We conducted a content analysis of a population of relevant English-language articles and transcripts (n = 125) produced by news organizations and publications in the U.S., Canada, Great Britain/Ireland, and Australia/New Zealand. We scored each article for the emphasis and appearance of 9 ethics-related themes. These were informed consent, welfare of the vulnerable, compensation, scientific progress, control/access, accountability/oversight, privacy, public education, and advocacy. Results The informed consent theme dominated media discussion, with almost 39.2 percent of articles/transcripts featuring the theme as a major focus and 44.8 percent emphasizing the theme as a minor focus. Other prominent themes and frames of reference focused on the welfare of the vulnerable (18.4 percent major emphasis; 36.0 percent minor emphasis), and donor compensation (19.2 percent major; 52.8 percent minor). Ethical themes that comprised a second tier of prominence included those of scientific progress, control/access, and accountability/oversight. The least prominent themes were privacy, public education, and advocacy. Conclusions The book has been praised as an opportunity to elevate media discussion of bioethics, but such claims should be re-considered. The relatively narrow focus on informed consent in the media discussion generated by Skloot’s book may limit the ability of

  2. Study of immortalization and malignant transformation of human embryonic esophageal epithelial cells induced by HPV18 E6E7.

    Science.gov (United States)

    Shen, Z; Cen, S; Shen, J; Cai, W; Xu, J; Teng, Z; Hu, Z; Zeng, Y

    2000-10-01

    In order to study the effect of viruses and tumor promoters on the tumorigenicity of the esophagus, human embryonic esophageal epithelial cells were infected with human papilloma virus HPV18 E6E7-AAV in synergy with 12-O-tetradecanoylphorbol 13-acetate (TPA) to observe their malignant transformation. The cultured esophageal epithelial cells incubated with HPV18 E6E7-AAV were divided into two groups: the SHEEC1 group was exposed to TPA (5 ng/ml) for 4 weeks at the 5th passage of the cells; the SHEE group served as the control and was cultured in the same medium without TPA. The morphological phenotype, the DNA content during the cell cycle and the chromosomes were analyzed. The tumorigenicity was assessed by colony formation after cultivation in soft agar and transplanting the cells into nude mice. HPV18 E6E7 DNA was assayed by fluorescent in situ hybridization (FISH) and the polymerase chain reaction (PCR). The SHEE group, at its 20th passage, grew as a monolayer with the cells showing anchorage dependence and contact inhibition. The chromosome analysis showed diploidy, and soft-agar cultivation and injection into nude mice showed the cells to be non-tumorigenic. They were therefore immortalized cells. In contrast, the SHEEC1 group (TPA group) showed increased DNA synthesis and a proliferative index that was higher (45%) than that of the SHEE group (34%). The number of large colonies of dense multilayer cells (positively transformed foci) in soft agar was high in SHEEC1 group (4.0%) but low in the SHEE group (0.1%). Tumors resulting from transplantation were observed in all six nude mice injected subcutaneously with cells of the SHEEC1 group but no tumor developed in mice receiving cells of the SHEE group. In both groups of cells, HPV18 E6E7 DNA was positively detected by FISH and PCR. The malignant transformation of human embryonic epithelial cells was induced in vitro by HPV18 E6E7 in synergy with TPA. This is a good evidence for the close relationship between

  3. Expression of a TGF-{beta} regulated cyclin-dependent kinase inhibitor in normal and immortalized airway epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Tierney, L.A.; Bloomfield, C.; Johnson, N.F. [and others

    1995-12-01

    Tumors arising from epithelial cells, including lung cancers are frequently resistant to factors that regulate growth and differentiation in normal in normal cells. Once such factor is transforming growth factor-{Beta} (TGF-{Beta}). Escape from the growth-inhibitory effects of TGF-{Beta} is thought to be a key step in the transformation of airway epithelial cells. most lung cancer cell lines require serum for growth. In contrast, normal human bronchial epithelial (NHBE) cells are exquisitely sensitive to growth-inhibitory and differentiating effects of TGF-{Beta}. The recent identification of a novel cyclin-dependent kinase inhibitor, p15{sup INK4B}, which is regulated by TGF-{Beta}, suggests a mechanism by which TGF-{Beta} mediates growth arrest in NHBE cells. The purpose of this study was two-fold: (1) to determine if p15{sup INK4B} is induced by TGF-{Beta} in NHBE cells or immortalized bronchial epithelial (R.1) cells and if that induction corresponds to a G1/S cell-cycle arrest; (2) to determine the temporal relationship between p15{sup INK4B} induction, cell-cycle arrest, and the phosphorylation state of the pRB because it is thought that p15{sup INK4B} acts indirectly by preventing phosphorylation of the RB gene product. In this study, expression of p15{sup INK4B} was examined in NHBE cells and R.1 cells at different time intervals following TGF-{Beta} treatment. The expression of this kinase inhibitor and its relationship to the cell and the pRb phosphorylation state were examined in cells that were both sensitive (NHBE) and resistant (R.1) to the effects of TGF-{Beta}. These results suggest that the cyclin-dependent kinase inhibitor, p15{sup INK4B}, is involved in airway epithelial cell differentiation and that loss or reduction of expression plays a role in the resistance of transformed or neoplastic cells to the growth-inhibitory effects of TGF-{Beta}.

  4. Immortalized mesenchymal stem cells: an alternative to primary mesenchymal stem cells in neuronal differentiation and neuroregeneration associated studies

    Directory of Open Access Journals (Sweden)

    Gong Min

    2011-11-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs can be induced to differentiate into neuronal cells under appropriate cellular conditions and transplanted in brain injury and neurodegenerative diseases animal models for neuroregeneration studies. In contrast to the embryonic stem cells (ESCs, MSCs are easily subject to aging and senescence because of their finite ability of self-renewal. MSCs senescence seriously affected theirs application prospects as a promising tool for cell-based regenerative medicine and tissue engineering. In the present study, we established a reversible immortalized mesenchymal stem cells (IMSCs line by using SSR#69 retrovirus expressing simian virus 40 large T (SV40T antigen as an alternative to primary MSCs. Methods The retroviral vector SSR#69 expressing simian virus 40 large T (SV40T antigen was used to construct IMSCs. IMSCs were identified by flow cytometry to detect cell surface makers. To investigate proliferation and differentiation potential of IMSCs, cell growth curve determination and mesodermal trilineage differentiation tests were performed. Neuronal differentiation characteristics of IMSCs were detected in vitro. Before IMSCs transplantation, we excluded its tumorigenicity in nude mice firstly. The Morris water maze tests and shuttle box tests were performed five weeks after HIBD models received cells transplantation therapy. Results In this study, reversible IMSCs were constructed successfully and had the similar morphology and cell surface makers as primary MSCs. IMSCs possessed better ability of proliferation and anti-senescence compared with primary MSCs, while maintained multilineage differentiation capacity. Neural-like cells derived from IMSCs had similar expressions of neural-specific genes, protein expression patterns and resting membrane potential (RMP compared with their counterparts derived from primary MSCs. There was no bump formation in nude mice subcutaneously injected with IMSCs. IMSCs

  5. Borehole locations and top surface altitudes of each of the 16 hydrostratigraphic layers of the Atlantic Coastal Plain of North and South Carolina (pp1773_unit_alt_boreholes)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Point data pp1773_unit_alt_boreholes represent the 309 locations of various types of boreholes that were used to determine the altitudes of each of the 16...

  6. [Lange, Thomas. Zwischen Reformation und Untergang Alt-Livlands. Der Rigaer Erzbischof Wilhelm von Brandenburg im Beziehungsgeflecht der livländischen Konföderation und ihrer Nachbarländer] / Madis Maasing

    Index Scriptorium Estoniae

    Maasing, Madis, 1984-

    2014-01-01

    Arvustus: Lange, Thomas. Zwischen Reformation und Untergang Alt-Livlands. Der Rigaer Erzbischof Wilhelm von Brandenburg im Beziehungsgeflecht der livländischen Konföderation und ihrer Nachbarländer

  7. Perennial roots to immortality.

    Science.gov (United States)

    Munné-Bosch, Sergi

    2014-10-01

    Maximum lifespan greatly varies among species, and it is not strictly determined; it can change with species evolution. Clonal growth is a major factor governing maximum lifespan. In the plant kingdom, the maximum lifespans described for clonal and nonclonal plants vary by an order of magnitude, with 43,600 and 5,062 years for Lomatia tasmanica and Pinus longaeva, respectively. Nonclonal perennial plants (those plants exclusively using sexual reproduction) also present a huge diversity in maximum lifespans (from a few to thousands of years) and even more interestingly, contrasting differences in aging patterns. Some plants show a clear physiological deterioration with aging, whereas others do not. Indeed, some plants can even improve their physiological performance as they age (a phenomenon called negative senescence). This diversity in aging patterns responds to species-specific life history traits and mechanisms evolved by each species to adapt to its habitat. Particularities of roots in perennial plants, such as meristem indeterminacy, modular growth, stress resistance, and patterns of senescence, are crucial in establishing perenniality and understanding adaptation of perennial plants to their habitats. Here, the key role of roots for perennial plant longevity will be discussed, taking into account current knowledge and highlighting additional aspects that still require investigation. PMID:24563283

  8. Cellular conservation of endangered midget buffalo (Lowland Anoa, Bubalus quarlesi) by establishment of primary cultured cell, and its immortalization with expression of cell cycle regulators.

    Science.gov (United States)

    Fukuda, Tomokazu; Iino, Yuuka; Eitsuka, Takahiro; Onuma, Manabu; Katayama, Masafumi; Murata, Koichi; Inoue-Murayama, Miho; Hara, Kumiko; Isogai, Emiko; Kiyono, Tohru

    2016-10-01

    Lowland Anoa has become endangered due to hunting and human activity. Protection and breeding of endangered species in a controlled environment is the best way of conservation. However, it is not possible to adopt this approach for all endangered species because of the cost involved and the ever-increasing number of critically endangered species. In consideration of these limitations to the conventional conservation methods, we established a primary cell culture of endangered buffalo (Lowland Anoa, Bubalus quarlesi), for the preservation of this biological resource. In addition, we introduced human derived, mutant cyclin dependent kinase 4 (CDK4), Cyclin D, and telomerase reverse transcriptase (TERT) into the primary cells. The successful introduction of these three genes was confirmed by western blot with specific antibodies, and enzymatic activity. We also showed that the expression of mutant CDK4, Cyclin D, and TERT allows us to efficiently establish an immortalized cell line, with an intact chromosome pattern, from Lowland Anoa. To the best of our knowledge, this study is the first investigation that established an immortalized cell line of an endangered wild animal species. PMID:27449922

  9. La aportación de Étienne Gilson al problema de la inmortalidad del alma humana en Cayetano / The Contribution of Étienne Gilson to the Problem of the Immortality of the Human Soul in Cajetan

    Directory of Open Access Journals (Sweden)

    Ceferino P. D. Muñoz

    2013-12-01

    Full Text Available In his article the author reviews Cajetan’s different positions on the prob-lem of the immortality of the human soul, and investigates possible reasons which led the Cardinal to dissent with the position of Thomas Aquinas. For this purpose, he invokes selected interpretations of distinguished scholars, with special reference to the approach of Étienne Gilson. Against the back-ground of his analyses the authors attempts to give a synthesis which, as he hopes, can become a modest contribution to contemporary comments on the thought of this great French medievalist about the problem of the immortality of the human soul in Cajetan.

  10. Synthesis and Properties of the Metallo-Supramolecular Polymer Hydrogel Poly[methyl vinyl ether-alt-mono-sodium maleate]∙AgNO3

    KAUST Repository

    Al-Dossary, Mona S.

    2014-05-01

    Gels are a special class of materials which are composed of 3D networks of crosslinked polymer chains that encapsulate liquid/air in the matrix. They can be classified into organogels or hydrogels (organic solvent for organogel and water for hydrogel). For hydrogels that contain metallic elements in the form of ions, the term of metallo-supramolecular polymer hydrogel (MSPHG) is often used. The aim of this project is to develop a kind of new MSPHG and investigate its properties and possible applications. The commercial polymeric anhydride poly(methyl vinyl ether-alt-maleic anhydride) (PVM/MA) is converted by reaction with NaOH to give poly(methyl vinyl ether-alt-monosodium maleate) (PVM/Na-MA). By addition of AgNO3-solution, the formation of the silver(I) supramolecular polymer hydrogel poly[methyl vinyl ether-alt-mono-sodium maleate]∙AgNO3 is obtained. Freeze-dried samples of the hydrogel show a mesoporous network of polycarboxylate ligands that are crosslinked by silver(I) cations. The supercritical CO2 dried silver(I) hydrogel was characterized by FT-IR, SEM-EDAX, TEM, TGA and Physical adsorption (BET) measurements. The intact silver(I) hydrogel was characterized by cryo-SEM. In the intact hydrogel, ion-exchange studies are reported and it is shown that Ag+ ions can be exchanged by copper(II) cations without disintegration of the hydrogel. The silver(I) hydrogel shows effective antibacterial activity and potential application as burn wound dressing.

  11. Decommissioning of the NUKEM-Alt facility. The decommissioning procedure adopted for the Hanau fuel element fabrication plants NUKEM-A and HOBEG

    International Nuclear Information System (INIS)

    The nuclear regulatory authority decided to provide for an optional participation of the public as far as the dismantling of the buildings of the NUKEM-Alt und HOBEG sites is concerned, while dismantling of the mechanical equipment of the two factories was judged to be subject to paragraph 7, sub-sec. 3 of Atomic Energy Act, not requiring participation of the public. As a result, the overall decommissioning plans had to be amended. The paper reports the current status of the licensing procedure and of the work for dismonthing of buildings. (DG)

  12. Influence of the composition of hydroxypropyl cellulose/maleic acid-alt-styrene copolymer blends on their properties as matrix for drug release

    Directory of Open Access Journals (Sweden)

    2009-05-01

    Full Text Available Poly(carboxylic acid-polysaccharide compositions have been found suitable for obtaining drug formulations with controlled release, most formulations being therapeutically efficacious, stable, and non-irritant. The influence of the characteristics of the aqueous solutions from which the polymer matrix is prepared (i.e. the total concentration of polymer in solutions and the mixing ratio between the partners, hydroxypropyl cellulose, HPC and maleic acid-alternating-styrene copolymer, MAc-alt-S on the kinetics of some drugs release in acidic environment (pH = 2 has been followed by ‘in vitro’ dissolution tests. It has been established that the kinetics of procaine hydrochloride release from HPC/MAc-alt-S matrix depends on its composition; the diffusion exponent, n is close to 0.5 for matrices where one of the components is in large excess and n~0.02 for middle composition range. The lower value of diffusion exponent for middle composition range could be caused by the so called ‘burst effect’, therefore the kinetic evaluation is difficult.

  13. Cross-Linked Hydrogels Formed through Diels-Alder Coupling of Furan- and Maleimide-Modified Poly(methyl vinyl ether-alt-maleic acid).

    Science.gov (United States)

    Stewart, S Alison; Backholm, Matilda; Burke, Nicholas A D; Stöver, Harald D H

    2016-02-23

    The Diels-Alder [4 + 2] cycloaddition between furan- and maleimide-functional polyanions was used to form cross-linked synthetic polymer hydrogels. Poly(methyl vinyl ether-alt-maleic anhydride) was reacted with furfurylamine or N-(2-aminoethyl)maleimide in acetonitrile to form pairs of furan- and maleimide-functionalized poly(methyl vinyl ether-alt-maleic acid)s. Mixtures of these mutually reactive polyanions in water gelled within 15 min to 18 h, depending on degree of functionalization and polymer concentrations. Solution and magic-angle spinning (1)H NMR were used to confirm the formation of the Diels-Alder adduct, to analyze competing hydrolytic side reactions, and demonstrate postgelation functionalization. The effect of the degree of furan and maleimide functionalization, polymer concentration, pH, and calcium ion concentration, on gelation time, gel mechanical properties, and equilibrium swelling, are described. Release of dextran as a model drug was studied using fluorescence spectroscopy, as a function of gel composition and calcium treatment. PMID:26800849

  14. Cu(II), Zn(II) andMn(II) complexes of poly(methyl vinyl ether-alt-maleic anhydride). Synthesis, characterization and thermodynamic parameters

    Indian Academy of Sciences (India)

    Hidayet Mazi; Ali Gulpinar

    2014-01-01

    The complexes of poly(methyl vinyl ether-alt-maleic anhydride) (poly(MVE-alt-MA)) with Zn(II), Mn(II) and Cu(II) ions were synthesized from the reaction of the aqueous solution of copolymer and metal(II) chlorides at different temperatures ranging from 25° to 40°C. Elemental analysis of themetal-polymer complexes suggests that the metal to ligand ratio is 1:1. The formation constants of each complex were determined by the mol-ratio method. UV-Vis studies showed that the complex formation tendency increased in the following order: Zn(II) > Cu(II) > Mn(II). This order was confirmed by the Irving-William series and Pearson’s classification. The IR spectral data indicated the metal ions to be coordinated through the hydroxyl groups of the hydrolysed maleic anhydride. The intrinsic viscosity and thermal properties of the copolymer and metal-polymer complexes and their thermal stability are discussed.

  15. Evaluation of matrix effects for serum ALT and AST measurements%血清ALT与AST测定的基质效应评价

    Institute of Scientific and Technical Information of China (English)

    郑松柏; 王建兵; 黄宪章; 马艳; 庄俊华; 徐宁; 周华友; 陈茶

    2011-01-01

    目的 评价7种室间质量评价(EQA)材料和4种市售材料在9个检测系统上测定血清ALT和AST的基质效应.方法 参照美国临床实验室标准化协会( CLSI) EP14-A2指南,根据ALT和AST的参考方法建立不含磷酸吡哆醛的比对方法.9个检测系统的常规方法为待评方法.用比对方法和待评方法同时测定新鲜人血清、EQA材料及市售材料的ALT和AST水平,评价非血清样品的基质效应.结果 ALT测定中1种EQA材料对所有检测系统均表现基质效应,AST测定中2种EQA材料对所有检测系统无基质效应,其他材料视系统的不同而表现出不同的情况.结论 基质效应影响血清ALT和AST测定的准确性和可比性,应充分重视基质效应对临床检验量值溯源的影响.%Objective To evaluate the matrix effects of measurement for alanine transaminase (ALT) and aspartate transaminase ( AST) in serum by using 7 materials of external quality assessment (EQA) and 4 commercial reference materials in 9 testing systems. Methods According to the Clinical and Laboratory Standards Institute (CLSI) EP14-A2 guideline and the reference methods of ALT and AST measurement, the comparative methods without pyridoxal 5-phosphate were developed. The routine measurement methods of 9 testing systems were the evaluated. The levels of ALT and AST in all fresh frozen serum samples, EQA materials and commercial mate rials were measured with the routine methods and the comparative methods, and the matrix effects of non-serum samples were evaluated simultaneously. Results For ALT measurements, one EQA material showed the matrix effects in all the routine analytical systems, and for AST measurements two EQA materials showed no matrix effect in all the routine analytical systems. Different matrix effects of other materials were observed in different routine analytical systems. Conclusion The accuracy and the comparability of ALT and AST measurement are affected by matrix effect. The

  16. Combined introduction of Bmi-1 and hTERT immortalizes human adipose tissue-derived stromal cells with low risk of transformation

    Energy Technology Data Exchange (ETDEWEB)

    Tatrai, Peter, E-mail: peter.tatrai@biomembrane.hu [Institute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Sciences, Karolina ut 29, H-1113 Budapest (Hungary); Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Egyetem ter 1, H-4032 Debrecen (Hungary); Szepesi, Aron, E-mail: aron.szepesi@biomembrane.hu [Creative Cell Ltd., Puskas Tivadar utca 13, H-1119 Budapest (Hungary); Matula, Zsolt, E-mail: matula.zsolt@gmail.com [Creative Cell Ltd., Puskas Tivadar utca 13, H-1119 Budapest (Hungary); Szigeti, Anna, E-mail: anna.szigeti@biomembrane.hu [Creative Cell Ltd., Puskas Tivadar utca 13, H-1119 Budapest (Hungary); Buchan, Gyoengyi, E-mail: buchan@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Egyetem ter 1, H-4032 Debrecen (Hungary); Madi, Andras, E-mail: madi@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Egyetem ter 1, H-4032 Debrecen (Hungary); Stem Cell, Apoptosis and Genomics Research Group of the Hungarian Academy of Sciences, University of Debrecen, Egyetem ter 1, H-4032 Debrecen (Hungary); Uher, Ferenc, E-mail: uher@biomembrane.hu [Stem Cell Laboratory, Hungarian National Blood Transfusion Service, Dioszegi ut 64, H-1113 Budapest (Hungary); and others

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer We immortalized human adipose stromal cells (ASCs) with hTERT, Bmi-1, and SV40T. Black-Right-Pointing-Pointer hTERT-only ASCs are prone to transformation, while Bmi-only ASCs become senescent. Black-Right-Pointing-Pointer SV40T introduced along with hTERT abrogates proliferation control and multipotency. Black-Right-Pointing-Pointer hTERT combined with Bmi-1 yields stable phenotype up to 140 population doublings. -- Abstract: Adipose tissue-derived stromal cells (ASCs) are increasingly being studied for their usefulness in regenerative medicine. However, limited life span and donor-dependent variation of primary cells such as ASCs present major hurdles to controlled and reproducible experiments. We therefore aimed to establish immortalized ASC cell lines that provide steady supply of homogeneous cells for in vitro work while retain essential features of primary cells. To this end, combinations of human telomerase reverse transcriptase (hTERT), murine Bmi-1, and SV40 large T antigen (SV40T) were introduced by lentiviral transduction into ASCs. The resulting cell lines ASC{sup hTERT}, ASC{sup Bmi-1}, ASC{sup Bmi-1+hTERT} and ASC{sup SV40T+hTERT} were tested for transgene expression, telomerase activity, surface immunomarkers, proliferation, osteogenic and adipogenic differentiation, karyotype, tumorigenicity, and cellular senescence. All cell lines have maintained expression of characteristic surface immunomarkers, and none was tumorigenic. However, ASC{sup Bmi-1} had limited replicative potential, while the rapidly proliferating ASC{sup SV40T+hTERT} acquired chromosomal aberrations, departed from MSC phenotype, and lost differentiation capacity. ASC{sup hTERT} and ASC{sup hTERT+Bmi-1}, on the other hand, preserved all essential MSC features and did not senesce after 100 population doublings. Notably, a subpopulation of ASC{sup hTERT} also acquired aberrant karyotype and showed signs of transformation after long-term culture

  17. Roughness threshold for cell attachment and proliferation on plasma micro-nanotextured polymeric surfaces: the case of primary human skin fibroblasts and mouse immortalized 3T3 fibroblasts

    Science.gov (United States)

    Bourkoula, A.; Constantoudis, V.; Kontziampasis, D.; Petrou, P. S.; Kakabakos, S. E.; Tserepi, A.; Gogolides, E.

    2016-08-01

    Poly(methyl methacrylate) surfaces have been micro-nanotextured in oxygen plasmas with increasing ion energy, leading to micro-nanotopography characterized by increased root mean square roughness, correlation length and fractal dimension. Primary human skin fibroblasts and mouse immortalized 3T3 fibroblasts were cultured on these surfaces and the number of adhering cells, their proliferation rate and morphology (cytoplasm and nucleus area) were evaluated as a function of roughness height, correlation length, and fractal dimension. A roughness threshold behavior was observed for both types of cells leading to dramatic cell number decrease above this threshold, which is almost similar for the two types of cells, despite their differences in size and stiffness. The results are discussed based on two theoretical models, which are reconciled and unified when the elastic moduli and the size of the cells are taken into account.

  18. Inefficiency in macromolecular transport of SCS-based microcapsules affects viability of primary human mesenchymal stem cells but not of immortalized cells

    DEFF Research Database (Denmark)

    Sanz-Nogués, Clara; Horan, Jason; Thompson, Kerry;

    2015-01-01

    mesenchymal stem cells (hMSCs). Human MSCs are of interest in regenerative medicine applications due to pro-angiogenic, anti-inflammatory and immunomodulatory properties, which result from paracrine effects of this cell type. In the present work we have encapsulated primary hMSCs and hMSC-TERT immortalized......, this applied to other primary cell cultures such as primary human fibroblasts but not to other cell lines such as human embryonic kidney 293 (HEK293) cells. We found that the microcapsule membrane had a molecular weight cut-off below a critical size, which caused impairment in the diffusion of essential......Microcapsules made of sodium cellulose sulphate (SCS) and poly-diallyl-dimethyl-ammonium chloride (pDADMAC) have been employed to encapsulate a wide range of established cell lines for several applications. However, little is known about the encapsulation of primary cells including human...

  19. On the Marriage State and Its Causes in Stories of Immortals%论《搜神记》中的婚姻状态及其成因

    Institute of Scientific and Technical Information of China (English)

    付优

    2011-01-01

    在志怪小说《搜神记》中,婚姻有三种状态,即缔结、存续或者破裂,分别表现为婚姻及时的伦理要求、秦晋匹也的夫妻关系以及劳燕分飞的最终结局,究其原因,无不与魏晋南北朝时期女性的生存状态有关。%In Stories of Immortals, there are three kinds of state of marriages: engagement, maintenance and divorce. They respectively reflect the timely demand of marriage, relationship between husband and wife, and the separation like birds flying in different directions. And their causes are closely related to the women's living conditions of Wei, Jin, South and North Dynasties.

  20. Human papillomavirus(HPV) oncogene-induced cell immortalization%人乳头瘤病毒癌基因诱导细胞永生化的研究进展

    Institute of Scientific and Technical Information of China (English)

    王珊珊; 王伟; 于莹莹; 李辉; 王宁

    2012-01-01

    永生化细胞是研究细胞增殖、分化、凋亡及衰老等的理想细胞模型.目前人类已建立多种细胞永生的方法,其中人乳头瘤病毒(HPV)癌基因(E6和E7)被广泛用于永生化细胞研究.E6蛋白和E7蛋白主要通过灭活p53通路和pRb通路,从多个水平提高端粒酶的表达和活性,使细胞逃过细胞复制衰老而继续增殖,实现细胞永生化.综述人乳头瘤病毒癌基因E6和E7的最新研究进展,探讨未来研究的趋势和研究方向.%Immortalized cell is the ideal cell model for studying cell proliferation, differentiation, apoptosis and aging. At present, a variety of methods for cell immortalization has been established, among them HPV oncogenes E6 and E7 are widely used in cell immortalization. The key role of oncoproteins E6 and E7 in cell immortalization is to inactivate p53 and pRb pathways, to improve telomerase expression and activity at multiple levels, which allow cells to escape from replicate Senescence and proliferate, and accomplish cell immortalization. This article reviews the advance in research of HPV oncoprotein-induced cell immortalization, and discusses the ongoing trends and future directions.

  1. Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-κB in immortalized and malignant oral keratinocytes

    Directory of Open Access Journals (Sweden)

    Lee Suk-Keun

    2007-09-01

    Full Text Available Abstract Background Interleukin-8 (IL-8 is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK and malignant human oral keratinocytes (HN12 cells with deferoxamine (DFO. Methods IL-8 production was measured by an enzyme-linked immunoabsorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR analysis. Electrophoretic mobility shift assays was used to determine NF-κB binding activity. Phosphorylation and degradation of the I-κB were analyized by Western blot. Results IHOK cells incubated with DFO showed increased expression of IL-8 mRNA, as well as higher release of the IL-8 protein. The up-regulation of DFO-induced IL-8 expression was higher in IHOK cells than in HN12 cells and was concentration-dependent. DFO acted additively with IL-1β to strongly up-regulate IL-8 in IHOK cells but not in HN12 cells. Accordingly, selective p38 and ERK1/2 inhibitors for both kinases abolished DFO-induced IL-8 expression in both IHOK and HN12 cells. Furthermore, DFO induced the degradation and phosphorylation of IκB, and activation of NF-κB. The IL-8 inducing effects of DFO were mediated by a nitric oxide donor (S-nitrosoglutathione, and by pyrrolidine dithiocarbamate, an inhibitor of NF-κB, as well as by wortmannin, which inhibits the phosphatidylinositol 3-kinase-dependent activation of NAD(PH oxidase. Conclusion This results demonstrate that DFO-induced IL-8 acts via multiple signaling pathways in immortalized and malignant oral keratinocytes, and that the control of IL-8 may be an important target for immunotheraphy against human oral premalignant lesions.

  2. Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-κB in immortalized and malignant oral keratinocytes

    International Nuclear Information System (INIS)

    Interleukin-8 (IL-8) is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK) and malignant human oral keratinocytes (HN12) cells with deferoxamine (DFO). IL-8 production was measured by an enzyme-linked immunoabsorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Electrophoretic mobility shift assays was used to determine NF-κB binding activity. Phosphorylation and degradation of the I-κB were analyized by Western blot. IHOK cells incubated with DFO showed increased expression of IL-8 mRNA, as well as higher release of the IL-8 protein. The up-regulation of DFO-induced IL-8 expression was higher in IHOK cells than in HN12 cells and was concentration-dependent. DFO acted additively with IL-1β to strongly up-regulate IL-8 in IHOK cells but not in HN12 cells. Accordingly, selective p38 and ERK1/2 inhibitors for both kinases abolished DFO-induced IL-8 expression in both IHOK and HN12 cells. Furthermore, DFO induced the degradation and phosphorylation of IκB, and activation of NF-κB. The IL-8 inducing effects of DFO were mediated by a nitric oxide donor (S-nitrosoglutathione), and by pyrrolidine dithiocarbamate, an inhibitor of NF-κB, as well as by wortmannin, which inhibits the phosphatidylinositol 3-kinase-dependent activation of NAD(P)H oxidase. This results demonstrate that DFO-induced IL-8 acts via multiple signaling pathways in immortalized and malignant oral keratinocytes, and that the control of IL-8 may be an important target for immunotheraphy against human oral premalignant lesions

  3. Altération par les sels des pierres de construction: Influence des propriétés capillaires et des conditions d'évaporation

    OpenAIRE

    Angeli, Matthieu; Bigas, Jean-Philippe; Menendez, Beatriz; Hébert, Ronan; David, Christian

    2006-01-01

    9 pages, compte rendu de conférence National audience L'importance de l'imbibition capillaire et des processus d'évaporation dans l'altération des pierres de construction sous l'action de la cristallisation des sels solubles est estimée par différents modes opératoires adaptés de la norme européenne EN 12370. Les différents tests consistent à modifier les conditions de l'apport en sel (sulfate de sodium) dans le réseau poreux des pierres ainsi que les possibilités d'évaporation, et de s...

  4. Synthesis of Cis,syndiotactic A-alt-B Copolymers from Two Enantiomerically Pure Trans-2,3-Disubstituted-5,6-Norbornenes

    Science.gov (United States)

    2016-01-01

    Cis,syndiotacticA-alt-B copolymers, where A and B are two enantiomerically pure trans-2,3-disubstituted-5,6-norbornenes with “opposite” chiralities, can be prepared with stereogenic-at-metal initiators of the type M(NR)(CHR′)(OR”)(pyrrolide). Formation of a high percentage of alternating AB copolymer linkages relies on an inversion of chirality at the metal with each propagating step and a relatively fast formation of an AB sequence as a consequence of a preferred diastereomeric relationship between the chirality at the metal and the chirality of the monomer. This approach to formation of an alternating AB copolymer contrasts dramatically with the principle of forming AB copolymers from achiral monomers and catalysts.

  5. Real time identification of drug-induced liver injury (DILI through daily screening of ALT results: a prospective pilot cohort study.

    Directory of Open Access Journals (Sweden)

    Helmi M'Kada

    Full Text Available OBJECTIVE: Identification of drug-induced liver disease (DILI is difficult, even among hospitalized patients. The aim of this pilot study was to assess the impact of a specific strategy for DILI screening. DESIGN: We prospectively compared the number of acute DILI cases identified in one week of a proactive strategy based on centralized elevated ALT values to those identified with a standard of care strategy for 24-week period based on referral cases to the hepatology unit. In the centralized strategy, a designated study biochemist identified patients with ALT greater than 3 times the upper limit of normal values (ULN and notified the designated hepatologists, who then went to the patients' wards, analyzed the charts, and if necessary, interviewed the identified patients. During these two periods, patients with possible DILI were included after signing an informed consent in an ongoing European diagnostic study (SAFE-T consortium. RESULTS: During the 24-week period of the standard strategy, 12 (0.04% patients out of a total of 28,145 were identified as having possible DILI, and 11 of these accepted to be included in the protocol. During the one-week proactive period, 7 patients out of a total of 1407 inpatients (0.498% [odds ratio vs. standard = 12.1 (95% CI, 3.9-32.3; P3 ULN by designated biochemists and hepatologists identified 12 times more acute cases of drug-induced liver disease than the standard strategy. This pilot cohort is registered on the number AP-HP P110201/1/08-03-2011 and AFSSAPS B110346-70.

  6. Synthesis and properties of the metallo-supramolecular polymer hydrogel poly[methyl vinyl ether-alt-mono-sodium maleate]·AgNO3: Ag+/Cu2+ ion exchange and effective antibacterial activity

    KAUST Repository

    Xu, Feng

    2014-01-01

    The commercial polymeric anhydride poly(methyl vinyl ether-alt-maleic anhydride) (PVM/MA) is converted by reaction with NaOH to give poly(methyl vinyl ether-alt-mono-sodium maleate) (PVM/Na-MA). By addition of AgNO 3-solution, the formation of the silver(i) supramolecular polymer hydrogel poly[methyl vinyl ether-alt-mono-sodium maleate]·AgNO 3 is reported. Freeze-dried samples of the hydrogel show a mesoporous network of polycarboxylate ligands that are crosslinked by silver(i) cations. In the intact hydrogel, ion-exchange studies are reported and it is shown that Ag+ ions can be exchanged by copper(ii) cations without disintegration of the hydrogel. The silver(i) hydrogel shows effective antibacterial activity and potential application as burn wound dressing. © the Partner Organisations 2014.

  7. Academic learning time in physical education (ALT-PE: is it related to fundamental movement skill acquisition and learning?. Tiempo de aprendizaje académico en educación física (ALT-PE: ¿tiene que ver con la adquisición y aprendizaje de habilidades motrices fundamentales?

    Directory of Open Access Journals (Sweden)

    Loza Olave, Edmundo

    2007-01-01

    Full Text Available AbstractIn this study, the relationship between time-variables of the physical education lesson and fundamental movement skill acquisition and learning was examined. One hundred and ten first grade students and their six physical educators participated. Students were pre-, post-, and re-tested both qualitatively and quantitatively on overhand throwing and catching. The Test of Gross Motor Development (Ulrich, 1985 was used for the assessment of qualitative skill performance and the Michigan Educational Assessment Program (MEAP, 1984 for the assessment of quantitative skill performance. Between pre- and post-tests students received an eight lessons unit instruction with emphasis on overhand throwing and catching. A total number of thirty-six students (6 students X 6 schools were selected, andtheir videotaped motor behavior in the lessons was analyzed with the Academic Learning Time ¿ Physical Education (ALT-PE,Parker, 1989. Regression analysis was applied to calculate students´ residual scores of achievement and to enable further data analysis. Correlation analysis between students´ achievement and ALT-PE categories indicated significant relationships between skill acquisition, learning and ALT-PE categories. It can be concluded that time devoted to practice skills, unlike times pent on activities irrelevant to the instructional task oron games, contributes to skill learning.ResumenEn este trabajo se estudia la relación entre variables temporales de las clases de Educación Física y la adquisición y aprendizaje de habilidades motrices fundamentales. En él participaron ciento diez alumnos de primer grado y seis profesores de Educación Física de Grecia. Los alumnos fueron examinados antes, durante y después tanto en términos cuantitativos como cualitativos en cuanto a lanzamientos y recepciones por encima de la cabeza. Se utilizó el Test de Desarrollo Motor Grueso (Ulrich, 1985 para evaluar el rendimiento en habilidades cualitativas y

  8. Gestionar dades en situacions d'emergència. Estudi del cas dels focs de l'Alt Empordà a Catalunya

    Directory of Open Access Journals (Sweden)

    Ortoll i Espinet, Eva

    2015-06-01

    Full Text Available Objectiu: analitzar el procés de la gestió de dades en una situació d'emergència des de la seva vessant comunicativa, tant pel que fa a la coordinació interna dels responsables de gestionar l'emergència com a la comunicació vers la ciutadania. -- Metodologia: estudi de cas (els focs de l'Alt Empordà a Catalunya amb un enfocament qualitatiu. L'obtenció i anàlisi de dades consisteix en: a entrevistes en profunditat a responsables de la gestió de l'emergència, b anàlisi de documentació oficial amb relació als plans d'acció, protocols i polítiques de comunicació i c anàlisi de dades generades durant l'emergència: comunicats interns, informes de seguiment dels plans oficials, talls de veu i comunicats a la població enviats des del perfil de Twitter @emergenciescat de la Direcció General de Protecció Civil de la Generalitat de Catalunya. -- Resultats: els responsables de coordinar la gestió d'emergències, en aquest cas dels focs de l'Alt Empordà a Catalunya, han hagut de gestionar una gran varietat d'actors i una gran diversitat de dades procedents de diferents fonts per complir la seva responsabilitat. L'estudi posa de manifest dos elements que han estat cabdals per garantir una gestió d'informació eficient durant el procés: el protocol d'actuació, Pla INFOCAT i la comunicació vers la població mitjançant el perfil de Twitter @emergenciescat. Malgrat l'èxit del nostre cas d'estudi, els resultats mostren interessants oportunitats de recerca per avançar en la gestió de dades en situacions d'emergència.Objetivo: analizar el proceso de la gestión de datos en una situación de emergencia desde su vertiente comunicativa, tanto en relación con la coordinación interna de los responsables de gestionar la emergencia como con la comunicación hacia la ciudadanía. --Metodología: estudio de caso (los fuegos del Alt Empordà en Cataluña con un enfoque cualitativo. La obtención y análisis de datos consiste en: a

  9. Cell bioenergetics in Leghorn male hepatoma cells and immortalized chicken liver cells in response to 4-hydroxy 2-nonenal-induced oxidative stress.

    Science.gov (United States)

    Piekarski, A L; Kong, B-W; Lassiter, K; Hargis, B M; Bottje, W G

    2014-11-01

    The major objectives of this study were to compare cell bioenergetics in 2 avian liver cell lines under control conditions and in response to oxidative stress imposed by 4-hydroxy 2-nonenal (4-HNE). Cells in this study were from a chemically immortalized Leghorn male hepatoma (LMH) cell line and a spontaneously immortalized chicken liver (CELi) cell line. Oxygen consumption rate (OCR) was monitored in specialized microtiter plates using an XF24 Flux Analyzer (Seahorse Bioscience, Billerica, MA). Cell bioenergetics was assessed by sequential additions of oligomycin, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), and antimycin-A that enables the determination of a) OCR linked to adenosine triphosphate (ATP) synthase activity, b) mitochondrial oxygen reserve capacity, c) proton leak, and d) nonmitochondrial cytochrome c oxidase activity. Under control (unchallenged) conditions, LMH cells exhibited higher basal OCR and higher OCR attributed to each of the bioenergetic components listed above compared with CELi cells. When expressed as a percentage of maximal OCR (following uncoupling with FCCP), LMH cells exhibited higher OCR due to ATP synthase and proton leak activity, but lower mitochondrial oxygen reserve capacity compared with CELi cells; there were no differences in OCR associated with nonmitochondrial cytochrome c oxidase activity. Whereas the LMH cells exhibited robust ATP synthase activity up to 50 μM 4-HNE, CELi cells exhibited a progressive decline in ATP synthase activity with 10, 20, and 30 μM 4-HNE. The CELi cells exhibited higher mitochondrial oxygen reserve capacity compared with LMH cells with 0 and 20 μM 4-HNE but not with 30 μM 4-HNE. Both cell lines exhibited inducible proton leak in response to increasing levels of 4-HNE that was evident with 30 μM 4-HNE for CELi cells and with 40 and 50 μM 4-HNE in LMH cells. The results of these studies demonstrate fundamental differences in cell bioenergetics in 2 avian liver-derived cell lines

  10. PCB153 reduces telomerase activity and telomere length in immortalized human skin keratinocytes (HaCaT) but not in human foreskin keratinocytes (NFK)

    Energy Technology Data Exchange (ETDEWEB)

    Senthilkumar, P.K. [Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA (United States); Robertson, L.W. [Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA (United States); Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA (United States); Ludewig, G., E-mail: Gabriele-ludewig@uiowa.edu [Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA (United States); Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA (United States)

    2012-02-15

    Polychlorinated biphenyls (PCBs), ubiquitous environmental pollutants, are characterized by long term-persistence in the environment, bioaccumulation, and biomagnification in the food chain. Exposure to PCBs may cause various diseases, affecting many cellular processes. Deregulation of the telomerase and the telomere complex leads to several biological disorders. We investigated the hypothesis that PCB153 modulates telomerase activity, telomeres and reactive oxygen species resulting in the deregulation of cell growth. Exponentially growing immortal human skin keratinocytes (HaCaT) and normal human foreskin keratinocytes (NFK) were incubated with PCB153 for 48 and 24 days, respectively, and telomerase activity, telomere length, superoxide level, cell growth, and cell cycle distribution were determined. In HaCaT cells exposure to PCB153 significantly reduced telomerase activity, telomere length, cell growth and increased intracellular superoxide levels from day 6 to day 48, suggesting that superoxide may be one of the factors regulating telomerase activity, telomere length and cell growth compared to untreated control cells. Results with NFK cells showed no shortening of telomere length but reduced cell growth and increased superoxide levels in PCB153-treated cells compared to untreated controls. As expected, basal levels of telomerase activity were almost undetectable, which made a quantitative comparison of treated and control groups impossible. The significant down regulation of telomerase activity and reduction of telomere length by PCB153 in HaCaT cells suggest that any cell type with significant telomerase activity, like stem cells, may be at risk of premature telomere shortening with potential adverse health effects for the affected organism. -- Highlights: ► Human immortal (HaCaT) and primary (NFK) keratinocytes were exposed to PCB153. ► PCB153 significantly reduced telomerase activity and telomere length in HaCaT. ► No effect on telomere length and

  11. Los visitantes del Parc Natural de l’Alt Pirineu y la práctica de actividades recreativo-deportivas. una propuesta de segmentación

    Directory of Open Access Journals (Sweden)

    Farías, E. I.

    2014-12-01

    Full Text Available In recent years there has been a large increase in the practice of recreational and sports activities in protected natural areas. As part of the planning and management of public use of these areas, is essential to a deeper understanding of the characteristics of the visitors. This study analyzes the characteristics of the different segments of visitors to Alt Pirineu Natural Park based on recreational and sports activities practiced. For this study, 1.600 surveys were conducted in 16 sampling points over a calendar year between the months of July 2010 and June 2011. In total we identified eight segments of visitors based on physical activity: walkers, recreational hikers, hikers, mountaineer, cyclists, mushroom picker, off road driver and skier. The results obtained here are discussed in terms of their possible applicability in the management of public use of this park and other protected natural areas and also for the development of management strategies and awareness campaigns aimed at different segments of visitors.En los últimos años se ha registrado un gran incremento en la práctica de las actividades recreativodeportivas en los espacios naturales protegidos. En el marco de la planificación y la gestión del uso público de este tipo de espacios, resulta fundamental profundizar en el conocimiento de las características de los visitantes. En este estudio se analiza el perfil de los diferentes segmentos de visitantes del Parc Natural de l’Alt Pirineu en base a las actividades recreativo-deportivas practicadas. Para este estudio se realizaron 1.600 encuestas en 16 puntos de muestreo, a lo largo de un año natural comprendido entre los meses de Julio de 2010 y Junio de 2011. En total se identificaron ocho segmentos de visitantes en función de la actividad física: paseantes, excursionistas, senderistas, montañistas, ciclistas, recolectores de setas, motoristas y esquiadores. Los resultados aquí obtenidos son discutidos en t

  12. 抗-HCV与HCV-RNA和ALT之间的关系探讨%Discussion on the Relationship of Anti-HCV, HCV-RNA and ALT

    Institute of Scientific and Technical Information of China (English)

    甸子芩; 沈云松

    2012-01-01

      目的探讨丙型肝炎病毒感染者丙型肝炎病毒抗体(抗-HCV)与丙型肝炎病毒核酸(HCV-RNA)和丙氨酸转氨酶(ALT)之间的关系.方法 对抗-HCV阳性样本441例,采用荧光定量聚合酶链反应(RT-PCR)检测HCV-RNA含量和其ALT水平.结果 441例抗-HCV阳性的血清中HCV-RNA阳性的有295例,阳性率67%,HCV-RNA阳性率随抗-HCV的S/CO值升高而升高.ALT异常的有269例,阳性率61%,ALT的含量及阳性率随HCV-RNA的含量升高而升高.结论 HCV-RNA的阳性率与抗-HCV的S/CO值存在正相关,ALT的阳性率及含量与HCV-RNA呈正相关,因此,可根据抗-HCV检测的S/CO值及ALT的含量辅助临床了解丙型肝炎病毒在体内的复制情况,以指导治疗.%  Objective To investigate the relationship of hepatitis C virus antibody (anti-HCV), hepatitis C virus RNA (HCV-RNA) and alanine amino transferase (ALT) in hepatitis C virus infection. Methods Using fluorescence quantitative polymerase chain reaction (RT-PCR) detecting HCV-RNA content and testing ALT levels in 441 cases of anti-HCV positive samples. Results In 441 cases of anti-HCV positive serum, HCV-RNA positive 295 cases, the positive rate of HCV-RNA was 67%, and the positive rate increased with the anti-HCV S/CO ratio increased. Abnormal ALT 269 cases, the positive rate of ALT was 61%, the content and the positive rate of ALT increased with HCV-RNA levels increased. Conclusion The positive rate of HCV-RNA has positive correlation with anti-HCV S/CO ratio, the positive rate and content of ALT has positive correlation with HCV-RNA, therefore, according to the anti-HCV S/CO ratio and the content of ALT assisted clinical understand the replication of hepatitis C virus in the body, to guide treatment.

  13. Multifunctional e-spun colloidal nanofiber structures from various dispersed blends of PVA/ODA-MMT with PVP/ODA-MMT, poly(VP-alt-MA and AgNPs incorporated polymer complexes as electro-active platforms

    Directory of Open Access Journals (Sweden)

    U. Bunyatova

    2016-07-01

    Full Text Available This work presented a new approach to fabricate polymer nanocomposites films with nanofiber structures from solution blends of poly(vinyl alcohol + octadecyl amine-montmorillonite (ODA-MMT (matrix with poly(N-vinylpyrrolidone + ODA-MMT (partner-1, poly(N-vinylpyrrolidone-alt-maleic anhydride ((poly(VP-alt-MA + (ODA-MMT (partner-2 and their silver (Ag-carrying polymer complexes by electrospinning. Chemical and physical structures, surface morphologies, thermal behaviors, electrical conductivity and thermal resistance parameters of nanofiber structures were investigated. Poly(VP-alt-MA was used both as a crosslinker and a donor of the hydrophilic groups such as ‒COOH and ‒NH–C=O amide from pyrrolidone ring. Reactive poly(VP-alt-MA, in situ generated Ag nanoparticles (AgNPs and original partner polymer had an significant effect on the morphology and diameter distribution of nanofibers. High and excellent conductive behaviors were observed for the homopolymer and copolymer of VP based fiber structures, respectively. Upon successive chemical cross-linking of the nanofiber structures by reactive partner copolymer, the conductivity of nanofiber films as electro-active platforms dramatically increased to 3.90·10–2 S·cm–1 at room temperature. Comparative analysis results also indicated that electrical properties strongly depended on the loaded reactive organoclay and in situ generated AgNPs.

  14. [Thomas Lange. Zwischen Reformation und Untergang Alt-Livlands : der Rigaer Erzbischof Wilhelm von Brandenburg im Beziehungsgeflecht der livländischen Konföderation und ihrer Nachbarländer] / Juhan Kreem

    Index Scriptorium Estoniae

    Kreem, Juhan, 1971-

    2015-01-01

    Arvustus: Lange, Thomas. Zwischen Reformation und Untergang Alt-Livlands : der Rigaer Erzbischof Wilhelm von Brandenburg im Beziehungsgeflecht der livländischen Konföderation und ihrer Nachbarländer (Hamburger Beiträge zur Geschichte des östlichen Europa)

  15. Comparison of immortalized bEnd5 and primary mouse brain microvascular endothelial cells as in vitro blood–brain barrier models for the study of T cell extravasation

    OpenAIRE

    Steiner, Oliver; Coisne, Caroline; Engelhardt, Britta; Lyck, Ruth

    2010-01-01

    Important insights into the molecular mechanism of T cell extravasation across the blood–brain barrier (BBB) have already been obtained using immortalized mouse brain endothelioma cell lines (bEnd). However, compared with bEnd, primary brain endothelial cells have been shown to establish better barrier characteristics, including complex tight junctions and low permeability. In this study, we asked whether bEnd5 and primary mouse brain microvascular endothelial cells (pMBMECs) were equally sui...

  16. ALT der er fortalt og ALT vi ved

    DEFF Research Database (Denmark)

    Toft, Herdis

    Rapport om en biblioteksforestilling udviklet i et samarbejde mellem Viborg Bibliotekerne og Carte Blanche, Egnsteater i Viborg, støttet af Statens Kunstråds Tværæstetiske Pulje og Kulturstyrelsen. I rapporten redegøres for projektets ide, design, forløb og evaluering. Afsnit omhandler Den poetiske...

  17. Pseudo-immortalization of postnatal cochlear progenitor cells yields a scalable cell line capable of transcriptionally regulating mature hair cell genes.

    Science.gov (United States)

    Walters, Brandon J; Diao, Shiyong; Zheng, Fei; Walters, Bradley J; Layman, Wanda S; Zuo, Jian

    2015-12-07

    The mammalian cochlea is a highly specialized organ within the inner ear. Sensory hair cells (HC) in the cochlea detect and transduce sound waves into electrical impulses that are sent to the brain. Studies of the molecular pathways regulating HC formation are hindered by the very sparse nature of HCs, where only ~3300 are found within an entire mouse cochlea. Current cell lines mimic certain aspects of HCs but lack terminal HC marker expression. Here we successfully "pseudo-immortalized" cochlear progenitor cells using the "conditional reprogramming" technique. These cells, termed "Conditionally Reprogrammed Otic Stem Cells" (CR-OSC), are able to bypass the senescence inherent to cochlear progenitor cells without genetic alterations, allowing for the generation of over 15 million cells from a single cochlea. These cells can be differentiated and up-regulate both early and terminal differentiation genes associated with HCs, including the terminal HC differentiation marker prestin. CR-OSCs also respond to known HC cues, including upregulation of HC genes in response to Atoh1 overexpression, and upregulation of prestin expression after thyroid hormone application. Overall, we describe the creation of a HC line capable of regulated expression of HC genes that can easily be recreated in any laboratory from any mouse of interest.

  18. An In Vitro System Comprising Immortalized Hypothalamic Neuronal Cells (GT1–7 Cells) for Evaluation of the Neuroendocrine Effects of Essential Oils

    Science.gov (United States)

    Mizuno, Dai; Konoha-Mizuno, Keiko; Mori, Miwako; Yamazaki, Kentaro; Haneda, Toshihiro; Koyama, Hironari; Kawahara, Masahiro

    2015-01-01

    Aromatherapy and plant-based essential oils are widely used as complementary and alternative therapies for symptoms including anxiety. Furthermore, it was reportedly effective for the care of several diseases such as Alzheimer's disease and depressive illness. To investigate the pharmacological effects of essential oils, we developed an in vitro assay system using immortalized hypothalamic neuronal cells (GT1–7 cells). In this study, we evaluated the effects of essential oils on neuronal death induced by hydrogen peroxide (H2O2), aluminum, zinc, or the antagonist of estrogen receptor (tamoxifen). Among tests of various essential oils, we found that H2O2-induced neuronal death was attenuated by the essential oils of damask rose, eucalyptus, fennel, geranium, ginger, kabosu, mandarin, myrrh, and neroli. Damask rose oil had protective effects against aluminum-induced neurotoxicity, while geranium and rosemary oil showed protective activity against zinc-induced neurotoxicity. In contrast, geranium oil and ginger oil enhanced the neurotoxicity of tamoxifen. Our in vitro assay system could be useful for the neuropharmacological and endocrine pharmacological studies of essential oils. PMID:26576190

  19. An In Vitro System Comprising Immortalized Hypothalamic Neuronal Cells (GT1-7 Cells) for Evaluation of the Neuroendocrine Effects of Essential Oils.

    Science.gov (United States)

    Mizuno, Dai; Konoha-Mizuno, Keiko; Mori, Miwako; Yamazaki, Kentaro; Haneda, Toshihiro; Koyama, Hironari; Kawahara, Masahiro

    2015-01-01

    Aromatherapy and plant-based essential oils are widely used as complementary and alternative therapies for symptoms including anxiety. Furthermore, it was reportedly effective for the care of several diseases such as Alzheimer's disease and depressive illness. To investigate the pharmacological effects of essential oils, we developed an in vitro assay system using immortalized hypothalamic neuronal cells (GT1-7 cells). In this study, we evaluated the effects of essential oils on neuronal death induced by hydrogen peroxide (H2O2), aluminum, zinc, or the antagonist of estrogen receptor (tamoxifen). Among tests of various essential oils, we found that H2O2-induced neuronal death was attenuated by the essential oils of damask rose, eucalyptus, fennel, geranium, ginger, kabosu, mandarin, myrrh, and neroli. Damask rose oil had protective effects against aluminum-induced neurotoxicity, while geranium and rosemary oil showed protective activity against zinc-induced neurotoxicity. In contrast, geranium oil and ginger oil enhanced the neurotoxicity of tamoxifen. Our in vitro assay system could be useful for the neuropharmacological and endocrine pharmacological studies of essential oils. PMID:26576190

  20. An In Vitro System Comprising Immortalized Hypothalamic Neuronal Cells (GT1–7 Cells for Evaluation of the Neuroendocrine Effects of Essential Oils

    Directory of Open Access Journals (Sweden)

    Dai Mizuno

    2015-01-01

    Full Text Available Aromatherapy and plant-based essential oils are widely used as complementary and alternative therapies for symptoms including anxiety. Furthermore, it was reportedly effective for the care of several diseases such as Alzheimer’s disease and depressive illness. To investigate the pharmacological effects of essential oils, we developed an in vitro assay system using immortalized hypothalamic neuronal cells (GT1–7 cells. In this study, we evaluated the effects of essential oils on neuronal death induced by hydrogen peroxide (H2O2, aluminum, zinc, or the antagonist of estrogen receptor (tamoxifen. Among tests of various essential oils, we found that H2O2-induced neuronal death was attenuated by the essential oils of damask rose, eucalyptus, fennel, geranium, ginger, kabosu, mandarin, myrrh, and neroli. Damask rose oil had protective effects against aluminum-induced neurotoxicity, while geranium and rosemary oil showed protective activity against zinc-induced neurotoxicity. In contrast, geranium oil and ginger oil enhanced the neurotoxicity of tamoxifen. Our in vitro assay system could be useful for the neuropharmacological and endocrine pharmacological studies of essential oils.

  1. Direct induction of hepatocyte-like cells from immortalized human bone marrow mesenchymal stem cells by overexpression of HNF4α.

    Science.gov (United States)

    Hu, Xiaojun; Xie, Peiyi; Li, Weiqiang; Li, Zhengran; Shan, Hong

    2016-09-16

    Hepatocytes from human bone marrow-derived mesenchymal stem cells (hBM-MSCs) are expected to be a useful source for cell transplantation. However, relatively low efficiency and repeatability of hepatic differentiation of human BM-MSCs remains an obstacle for clinical translation. Hepatocyte nuclear factor 4 alpha (HNF4α), a critical transcription factor, plays an essential role in the entire process of liver development. In this study, immortalized hBM-MSCs, UE7T-13 cells were transduced with a lentiviral vector containing HNF4α. The typical fibroblast-like morphology of the MSCs changed, and polygonal, epithelioid cells grew out after HNF4α transduction. In hepatocyte culture medium, HNF4α-transduced MSCs (E7-hHNF4α cells) strongly expressed the albumin (ALB), CYP2B6, alpha-1 antitrypsin (AAT), and FOXA2 mRNA and exhibited morphology markedly similar to that of mature hepatocytes. The E7-hHNF4α cells showed hepatic functions such as Indocyanine green (ICG) uptake and release, glycogen storage, urea production and ALB secretion. Approximately 28% of E7-hHNF4α cells expressed both ALB and AAT. Furthermore, these E7-hHNF4α cells via superior mesenteric vein (SMV) injection expressed human ALB in mouse chronic injured liver. In conclusion, this study represents a novel strategy by directly inducing hepatocyte-like cells from MSCs. PMID:27501760

  2. Changes of gene methylation profile in malignant transformation of immortalized human bronchial epithelial cell line induced by alpha-particle irradiation

    International Nuclear Information System (INIS)

    Objective: To identify the changes of DNA methylation profile in the process of malignant transformation of BEP2D cell induced by α particles. Methods: The genomic DNAs were isolated from the malignant transformation BERP35T4 cells and immortalized human bronchial epithelial cell line BEP2D. Genomic DNAs were digested by MseI and ligated of PCR linkers. Methylated DNAs were digested by BstUI and amplified by PCR. The methylated DNA probes were prepared by labeling with Cy3 and Cy5 fluorescence dyes individually and hybridized to the methylation CpG-Island microarray. The hybridization results were scanned and analyzed. Intensity values were quality controlled and normalized. The normalized data were used to identify the differentially expressed genes based on a 1.5 fold difference of the expression level. Results: There were 16 genes which showed changes of methylation level in malignant transformation BERP35T4 cells, 9 of them were hyper methylation and 7 were hypo methylation. These genes were including the SKIP gene, PPP3CC gene, MAP2K6 gene, KIR2DL1 gene, KIR2DL4 gene, KIR3DP1 gene, ZNF493 gene, ZNF100 gene, NKX2-5 gene, TFAP2D gene, DR1 gene, KCNJ16 gene, CCDC18 gene, FNBP1L gene, IRX4 gene, EPB41L3 gene, TCP10 gene and so on. Conclusions: The DNA methylation might have effects on ionizing radiation derived tumorigenesis. (authors)

  3. Type I interferon reaction to viral infection in interferon-competent, immortalized cell lines from the African fruit bat Eidolon helvum.

    Directory of Open Access Journals (Sweden)

    Susanne E Biesold

    Full Text Available Bats harbor several highly pathogenic zoonotic viruses including Rabies, Marburg, and henipaviruses, without overt clinical symptoms in the animals. It has been suspected that bats might have evolved particularly effective mechanisms to suppress viral replication. Here, we investigated interferon (IFN response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. helvum. Immortalized cell lines were generated; their potential to induce and react on IFN was confirmed, and biological assays were adapted to application in bat cell cultures, enabling comparison of landmark IFN properties with that of common mammalian cell lines. E. helvum cells were fully capable of reacting to viral and artificial IFN stimuli. E. helvum cells showed highest IFN mRNA induction, highly productive IFN protein secretion, and evidence of efficient IFN stimulated gene induction. In an Alphavirus infection model, O'nyong-nyong virus exhibited strong IFN induction but evaded the IFN response by translational rather than transcriptional shutoff, similar to other Alphavirus infections. These novel IFN-competent cell lines will allow comparative research on zoonotic, bat-borne viruses in order to model mechanisms of viral maintenance and emergence in bat reservoirs.

  4. Quantitative assessment of the relative antineoplastic potential of the n-butanolic leaf extract of Annona muricata Linn. in normal and immortalized human cell lines.

    Science.gov (United States)

    George, V Cijo; Kumar, D R Naveen; Rajkumar, V; Suresh, P K; Kumar, R Ashok

    2012-01-01

    Natural products have been the target for cancer therapy for several years but there is still a dearth of information on potent compounds that may protect normal cells and selectively destroy cancerous cells. The present study was aimed to evaluate the cytotoxic potential of n-butanolic leaf extract of Annona muricata L. on WRL-68 (normal human hepatic cells), MDA-MB-435S (human breast carcinoma cells) and HaCaT (human immortalized keratinocyte cells) lines by XTT assay. Prior to cytotoxicity testing, the extract was subjected to phytochemical screening for detecting the presence of compounds with therapeutic potential. Their relative antioxidant properties were evaluated using the reducing power and DPPH* radical scavenging assay. Since most of the observed chemo-preventive potential invariably correlated with the amount of total phenolics present in the extract, their levels were quantified and identified by HPLC analysis. Correlation studies indicated a strong and significant (PAnnona muricata. Isolation of the active metabolites from the extract is in prospect.

  5. Mapping of QTL for tiller number at different stages of growth in wheat using double haploid and immortalized F2 populations

    Indian Academy of Sciences (India)

    Zhuokun Li; Tao Peng; Quangang Xie; Shuxiao Han; Jichun Tian

    2010-12-01

    Effective tiller number is one of the most important traits for wheat (Triticum aestivum L.) yield, but the inheritance of tillering is poorly understood. A set of 168 doubled haploid (DH) lines derivatives of a cross between two winter wheat cultivars (Huapei 3 and Yumai 57), and an immortalized F2 (IF2) population generated by randomly permutated intermating of these DHs were investigated, and QTLs of tillering related to the maximum tillering of pre-winter (MTW), maximum tillering in spring (MTS), and effective tillering in harvest (ETH) were mapped. Phenotypic data were collected for the two populations from two different environments. Using inclusive composite interval mapping (ICIM), a total of 9 and 18 significant QTL were detected across environments for tillering in the DH and IF2 populations, respectively. Four QTLs were common between two populations. A major QTL located on the 5D chromosome with the allele originating from Yumai 57 was detected and increased 1.92 and 3.55 tillers in MTW and MTS, respectively. QTLs (QMts6D, QEth6D) having a neighbouring marker interval at Xswes679.1 and Xcfa2129 on chromosome 6D was detected in MTS and ETH. These results provide a better understanding of the genetic factors for selectively expressing the control of tiller number in different growth stages and facilitate marker-assisted selection strategy in breeding.

  6. John Keat's Pursuit of Immortality in His Odes%济慈永恒理想在颂歌中的体现

    Institute of Scientific and Technical Information of China (English)

    苑辉

    2001-01-01

    济慈的颂歌在理性与艺术方面取得了显著的进步,通常被认为是济慈天才的最自然、最高超的表达,坦露了他内心的爱与抱负.为实现艺术美的永恒,济慈尽最大的努力提高他的写作技巧,在颂歌中运用了大量的富有创造性的想象以表达他内心的这种真实.在这个世界上"美即是真,真即是美",这是我们知道的,并且应该知道的.%John Keats, who achieved remarkable intellectual and artistic development. His odles are usually considered to be the most natural and highest expression of his genius. Bearing love and Ambition in his heart,John Keats made all his effort to improve his skills of writing in order toi reach the immortal beauty of art. Keats employed many creative images to help to express his eternal truth. "Beauty is Truth, Truth is Beauty" ,that is what we know and should know in the world.

  7. Post-irradiation time effects on the graft of poly(ethylene-alt-tetrafluoroethylene) (ETFE) films for ion exchange membrane application

    International Nuclear Information System (INIS)

    Grafting of styrene followed by sulfonation onto poly(ethylene-alt-tetrafluoroethylene) (ETFE) was studied for synthesis of ion exchange membranes. Radiation-induced grafting of styrene onto ETFE films was investigated after simultaneous irradiation (in post-irradiation condition) using a 60Co source. The ETFE films were irradiated at 20 kGy dose at room temperature and chemical changes were monitored after contact with styrene for grafting. The post-irradiation time was established at 14 days when the films were remained in styrene/toluene 1:1 v/v. After this period the grafting degree was evaluated in the samples. The grafted films were sulfonated using chlorosulfonic acid and 1, 2-dichloroethane 20:80 (v/v) at room temperature for 5 h. The membranes were analyzed by infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), thermogravimetric measurements (TG) and degree of grafting (DOG). The ion exchange capacity (IEC) of membranes was determined by acid-base titration and the values for ETFE membranes were achieved higher than Nafion films. Preliminary single cell performance was made using pure H2 and O2 as reactants at a cell temperature of 80 deg. C and atmospheric gas pressure. The fuel cell performance of ETFE films was satisfactory when compared to state-of-art Nafion membranes.

  8. Altı Sigma yönteminin zeytinyağı sektöründe bir uygulaması

    OpenAIRE

    Biçer Oymak, Bihter

    2015-01-01

    Müşteri istek ve gereksinimlerinin çok yüksek olduğu ve sürekli değişimin yaşandığı iş dünyasında, organizasyonların faaliyetlerini sürdürebilmeleri için sadece üretim yapıp, pazarlaması yeterli olmamaktadır. Her işlevini sürekli iyileştiren ve yaptığıyla yetinmeyip sürekli daha yüksek hedefleri olup müşterilerinin istek ve ihtiyaçlarının üstüne çıkan organizasyonlar, büyük rekabet avantajı sağlamaktadır. Dünyaca ünlü organizasyonlar sürekli iyileştirmenin gereğini anlayıp özellikle Altı Sigm...

  9. Gestionar dades en situacions d'emergència. Estudi del cas dels focs de l'Alt Empordà a Catalunya

    Directory of Open Access Journals (Sweden)

    Ortoll i Espinet, Eva

    2015-06-01

    Methodology: The researchers conducted a qualitative study of fire management in the Catalan region of Alt Empordà. The retrieval and analysis of data consisted in: a detailed interviews with emergency managers, b the analysis of the official documentation outlining action plans, procedures and communication policies and c the analysis of the data generated during an emergency: internal communication, reports on following official plans, public announcement equipment and communication with the civilian community using the Twitter profile @emergenciescat of the Catalan civil defence service the Direcció General de Protecció Civil de la Generalitat de Catalunya. -- Results: The agents needed to manage a wide range of emergency responders and data from many sources in order to discharge their responsibilities. The study shows that during an emergency, two aspects of management are critical: the action plan, which in this case was Pla INFOCAT, and communication with the civilian community, which in this case was directed using the Twitter profile @emergenciescat. In spite of the success of our case study, the results indicate that further research could help improve data management in emergency situations.

  10. SV40TAg和Cre/loxP系统诱导的正常人可逆性转化黑素细胞在豚鼠体内的存活能力和复色实验%Survival and melanogenic potential of reversibly immortalized human melanocytes mediated by SV40T antigen gene and Cre/loxP system in Guinea pigs

    Institute of Scientific and Technical Information of China (English)

    王鹰; 曾志华; 杨希川; 郝飞; 钟白玉

    2010-01-01

    melanocyte distribution and melanin deposition in epidermis. Results Repigmentation started 4 weeks after the transplantation, and dark or brown patches, which ranged in size from 0.5 to 1 cm, were observed in the implanted area 3 months after the transplantation. The repigmentation rate was of no significant difference between pigs transplanted with MCTC and those with primary melanocytes (82.5% vs 76.7%, P > 0.05). Pathological examination revealed melanin deposition in the basal layer of epidermis and some hair follicles in transplanted area. Conclusions SV40T antigen gene combined with Cre/loxP site-specific recombinase system can induce the reversible immortalization of human melanocytes, and the immortalized melanocytes have a favorable profile of biological safety and similarity in survival rate and melanogenic potential to primary melanocytes.

  11. Rangelia vitalii: changes in the enzymes ALT, CK and AST during the acute phase of experimental infection in dogs Rangelia vitalii: mudanças nas enzimas ALT, CK e AST na fase aguda da infecção experimental em cães

    Directory of Open Access Journals (Sweden)

    Márcio Machado Costa

    2012-09-01

    Full Text Available Rangelia vitalii is a protozoon that causes diseases in dogs, and anemia is the most common laboratory finding. However, few studies on the biochemical changes in dogs infected with this protozoon exist. Thus, this study aimed to investigate the biochemical changes in dogs experimentally infected with R. vitalii, during the acute phase of the infection. For this study, 12 female dogs (aged 6-12 months and weighing between 4 and 7 kg were used, divided in two groups. Group A was composed of healthy dogs (n = 5; and group B consisted of infected animals (n = 7. Blood samples were collected on days 0, 10, 20 and 30 after infection, using tubes without anticoagulant to obtain serum and analyze the biochemical parameters. An increase in alanine aminotransferase (ALT on day 20 (P Rangelia vitalii é um protozoário que causa doença em cães, sendo a anemia o achado laboratorial mais frequente. No entanto, existem poucos estudos sobre as alterações bioquímicas em cães infectados com o protozoário. Assim, este estudo tem como objetivo investigar as alterações bioquímicas de cães experimentalmente infectados com R. vitalii na fase aguda da infecção. Para o estudo, foram utilizados 12 cães fêmeas (com idade entre 6 a 12 meses e peso entre 4 a 7 kg, divididos em dois grupos. O grupo A (n = 5 foi composto de animais saudáveis e o grupo B (n = 7 de animais infectados. Amostras de sangue foram coletadas nos dias zero, dez, vinte e trinta PI, utilizando tubos sem anticoagulante para obtenção de soro e análise dos parâmetros bioquímicos. Foi observado um aumento na alanino aminotransferase (ALT no dia 20 PI (P < 0,05 e aumento na creatinoquinase (CK e aspartato aminotransferase (AST em todo o período experimental (P < 0,05. Não foram observadas alterações séricas na gama-glutamiltransferase, uréia e creatinina. Portanto, é possível concluir que a infecção experimental por R. vitalii causa alterações no perfil bioquímico, com

  12. Gicht: Alte Erkrankung - neue Therapie

    Directory of Open Access Journals (Sweden)

    Gruber J

    2009-01-01

    Full Text Available Die Gicht ist eine chronische Arthritis und kann zu einer signifikanten Beeinträchtigung der Lebensqualität führen. Die Ursache der Gicht ist schon lange bekannt und kann meist mit den herkömmlichen Medikamenten gut therapiert werden. Urikostatika reduzieren die Harnsäure durch Hemmung der Produktion, Urikosurika führen zur gesteigerten renalen Ausscheidung von Harnsäure. Das am meisten gebrauchte Urikostatikum ist Allopurinol, das aber in der empfohlenen Dosis oft die Harnsäure nicht entsprechend senkt und auch potenziell ein – im Einzelfall – letales Nebenwirkungsspektrum hat. Auch der Gebrauch der Urikosurika ist limitiert. In den vergangenen Jahren wurden neue Medikamente zur Behandlung der Gicht entwickelt. Als mögliche Alternative böte sich Febuxostat, ein nicht purinanaloges Urikostatikum, an; es ist aber noch nicht zugelassen. Insbesondere bei der Behandlung der tophösen Gicht könnte sich der Einsatz von Rasburicase, das Harnsäure in das besser wasserlösliche Allantoin umwandelt, bewähren. Als ein gutes Beispiel der translationalen Forschung ist die Inhibierung von IL-1 zu sehen. Diese eröffnet neue Wege zur Therapie der Gicht, insbesondere wo die konventionellen Therapeutika entweder versagen oder eine Kontraindikation gegeben ist.

  13. pH and ionic strength-sensitive drug release from poly (L-lysine-alt-terephthalic acid) microcapsules: effects of dissociable groups on the microcapsule structure; pH to ion kyodo ni otoshita poly(L-lysine-alt-terephthal san) microcapsule kara no yakubutsu hoshutsu seigyo

    Energy Technology Data Exchange (ETDEWEB)

    Makino, K. [Science University of Tokyo, Tokyo (Japan). Faculty of Pharmaceutical Science

    1995-12-15

    Poly(L-lysine-alt-terephthalic acid) microcapsules change their particle size, volume and the membrane permeability, depending on pH and the ionic strength. The mechanisms of the change in membrane shape were studied. The water content in the membrane and the sensitivity to the stimuli changed corresponding to the changes in the charge density and in the hydrophobicity of the membrane. These phenomena were considered as the phase transition of a hydrogen. In aqueous solutions, the microcapsules shrank by the addition of multi-valent cations or by the addition of the solvent with low permittivity such as ethanol. The viscosity of the membrane was high when the water content of the microcapsules was high. Also, the mass density of the membrane was inversely proportional to the microcapsule size. 4 refs., 3 figs.

  14. 聚(乳酸-天冬氨酸)的合成及性能研究%The Synthesis and Property Study of the Poly(Lactide-alt-Aspartic Acid)

    Institute of Scientific and Technical Information of China (English)

    余飞; 刘文明

    2013-01-01

    3-[(benzyloxycarbonyl) methyl] morpholine-2,5-dione (MMD) was synthesized via aspartic acid and chloroacetyl chloride as the raw materials.Afterwards,poly(lactide-alt-aspartic acid) was obtained by copolymerizing lactide and MMD of which structure was confirmed by FTIR,1 H-NMR.Effects of catalyst amount,polymerization time and temperature on the inherent viscosity of the product were studied.In addition,the water absorption and degradation between this copolymer and PLA were investigated.It was revealed that at 160 ℃ for 8 h,with 0.3% (wt) catalyst amount of the total reactants,co-polymer with the highest inherent viscosity can be achieved.The synthesized copolymer in this paper had improved water absorption and weight loss rate in comparison with PLA.%以天冬氨酸和氯乙酰氯为原料合成了3-[(苄氧羰基)-甲基]-吗啉-2,5-二酮,再与丙交酯共聚合成聚(乳酸-天冬氨酸),并用FTIR、1H NMR对其进行结构表征.研究了3-[(苄氧羰基)-甲基]-吗啉-2,5-二酮与丙交酯的共聚反应,探讨了不同催化剂用量、聚合时间、聚合温度对聚合物特性黏数的影响;并对共聚物与PLA的亲水性以及降解性能进行了对比.结果表明,催化剂用量为反应物质量的0.3%,聚合时间8h,聚合温度160℃时,共聚物的特性黏数最大;改性后的聚乳酸亲水性能、降解性能都优于聚乳酸.

  15. HCV -RNA 与 HCV -Ab、ALT、TP 相关性研究%The Relativity Analysis of HCV-RNA, HCV-Ab, ALT and TP from Hepatitis C Patients

    Institute of Scientific and Technical Information of China (English)

    李昕; 管世鹤

    2015-01-01

    探讨丙型肝炎患者体内 HCV -RNA、HCV -Ab、ALT 和 TP 间的相互关系。采用ELISA检测708例HCV-Ab阳性的丙型肝炎疑似患者,以RT-PCR检测血清HCV-RNA载量,全自动生化仪定量检测ALT和TP。 HCV-Ab表达水平与HCV-RNA载量有关,HCV-RNA载量与ALT异常率呈正相关性,但HCV-RNA载量与ALT含量无相关性,与TP含量亦无相关性。708例HCV-Ab阳性患者中男性多于女性,差异无统计学意义( P>0.05);40岁以上患者比例多于40岁以下患者比例,差异有统计学意义( P<0.05)。 HCV-RNA与HCV-Ab、ALT具有一定相关性,丙型肝炎以40岁以上男性患者多见,应引起临床重视。%In order to investigate the relativity among HCV -RNA, HCV-Ab, ALT and TP in hepatitis C pa-tients, 708 suspected hepatitis C patients with HCV -Ab positive were checked by using the ELISA method , with real-time detecting HCV-RNA in those bloods by Fluorescentrt -PCR, ALT and TP detected by automat-ic biochemical analyzer .The test results showed that HCV -Ab expression level is related with HCV -RNA con-tent.HCV-RNA content is positively correlated with abnormal rate of ALT .But HCV-RNA content is not cor-related with ALT content and TP content .Among the 708 patients, the HCV-Ab positive percentage of men is more than women , and there is no statistically significant difference ( P>0 .05 );the ratio of the ≥40 years old patients is greater than <40 years old patients, and the difference is statistically significant (P<0.05).HCV-RNA, HCV-Ab and ALT have certain relativity .Among hepatitis C patients men of over 40 years old are more , and should be paid more clinical attention .

  16. DELIMITAREA DENUNŢĂRII FALSE ŞI A DECLARAŢIEI MINCINOASE, A CONCLUZIEI FALSE SAU TRADUCERII INCORECTE DE ALTE INFRACŢIUNI CONEXE

    Directory of Open Access Journals (Sweden)

    Anastasia GÎRLEA

    2015-11-01

    Full Text Available În articol este tratat subiectul privind delimitarea denunţării false şi a declaraţiei mincinoase, a concluziei false sau traducerii incorecte de alte infracţiuni conexe. Este analizată conexiunea infracţiunii de denunţare falsă (art. 311 CP RM cu declaraţia mincinoasă, concluzia falsă sau traducerea incorectă (art.312 CP RM, cu infracţiunea de comunicare mincinoasă cu bună ştiinţă despre actul de terorism (art.281 CP RM şi cu infracţiunea de falsificare a probelor în procesul penal (art.310 alin.(2 CP RM, precum şi a declaraţiei mincinoase, concluziei false sau traducerii incorecte (art.312 CP RM în raport cu infracţiunile de refuz sau eschivare a martorului ori a părţii vătămate de a face declaraţii (art.313 CP RM şi de eschivare a expertului de a face concluzii, a interpretului sau a traducătorului de a face interpre-tări ori de a face traduceri (art.314 CP RM. Conexitatea infracţiunilor este analizată prin prisma similitudinilor şi dife-renţelor ce le sunt specifice. Acestea se referă la: obiectul juridic; conţinutul faptei (acţiunii sau inacţiunii prejudicia-bile; alte semne ale laturii obiective a infracţiunii; tipul componenţei de infracţiune în funcţie de rezultatul infracţiunii (componenţă materială; momentul de consumare a infracţiunii; motivul şi scopul infracţiunii.DELIMITATION BETWEEN FALSE DENUNCIATIONS, UNTRUTH STATEMENT AND FALSE CONCLUSIONS OR INCORRECT TRANSLATIONS FROM OTHER SIMILAR CRIMESThis article refers to the delimitation between the crime of false denunciation and untruth statement, false conclusions or incorrect translation from other similar crimes. The author analyzes the connection between the crimes of false denun-ciation (art. 311 CC of RM and crime of untruth statement, false conclusion and incorrect translation (art. 312 CC of RM, crime of deliberately untruth communication about the terrorist act (art. 281 CC of RM and the crime of evidence falsification in

  17. Bazı yağ altı sularının uçucu bileşikleri ve mikrobiyal kontrolleri

    Directory of Open Access Journals (Sweden)

    Neşe Kırımer

    2012-01-01

    Full Text Available Ülkemizde halk arasında yaygın olarak kullanılmakta olan yağ altı sularının kontrol ve standardizasyonu için yapılmış araştırma sayısı yok denecek kadar azdır. Bu konudaki eksikliği kısmen giderebilmek için Eskişehir'de ticari potansiyeli yüksek olan ve market raflarından kolaylıkla ulaşılabilen başta gül ve kekik suyu olmak üzere hayıt, karabaş, melisa, ökaliptus ve papatya sularının n-hekzan ile sıvı-sıvı ekstraksiyonu yapılarak elde edilen uçucu bileşikler fraksiyonunun Gaz Kromatografisi (GK ve Gaz Kromatografisi/Kütle Spektrometresi (GK/KS analizleri gerçekleştirilmiştir ve membran filtrasyon yöntemi ile mikrobiyal kirlilikleri kontrol edilmiştir.GK/KS sonuçlarına göre; gül suyunda fenil etil alkol, geraniol, sitronellol; hayıt, karabaş, kekik ve papatya sularında karvakrol; melisa suyunda öjenol; ökaliptus suyunda ise 1,8-sineol ve kafur yağ altı sularında ana bileşikler olarak belirlenmiştir. Papatya suyunun bileşimine bakıldığında ise ilginç olarak ana maddenin %32 oranla karvakrol olduğu görülmüştür. Yapılan mikrobiyolojik kontrollerde ise bazı markalara ait gül ve melisa sularının yüksek seviyede bakteri kontaminasyonuna sahip olduğu gözlenmiş, özellikle Melisa suyunda fekal koliform, kolifrom ve P. aeruginosa bakterilerinin standartların üzerinde olduğu belirlenmiştir. Halkımızın hekim ve eczacısına danışmadan kontrolsüz olarak dâhilen tükettiği bu ve benzeri ürünlerin üretim izni ve kontrollerinin en kısa sürede Sağlık Bakanlığı izin ve denetimine verilmesi önerilmektedir.

  18. Transcriptional profiling of immortalized and K-ras-transformed mouse fibroblasts upon PKA stimulation by forskolin in low glucose availability.

    Science.gov (United States)

    Chiaradonna, Ferdinando; Pirola, Yuri; Ricciardiello, Francesca; Palorini, Roberta

    2016-09-01

    Forskolin (FSK) induces activation of protein kinase A (PKA). This activation protects specifically some cancer cells from death induced by glucose starvation. Cell effects upon FSK treatment prompted us to investigate in detail the physiological role of PKA in the activation of pro-survival mechanisms in glucose starvation. In this regard we performed a microarray analysis of normal NIH3T3 and transformed NIH3T3-K-ras mouse fibroblasts cultured at 1 mM glucose and daily treated or not with 10 μM FSK until 72 h of growth, when the samples were collected. The microarray is deposited into Gene Expression Omnibus under Series GSE68266. The microarray data revealed that the activation of PKA regulates the expression of genes involved in metabolic, stress-response and pro-survival processes, like glutamine metabolism, autophagy and unfolded protein response, preventing cancer cell death in glucose starvation. Altogether these findings suggest that PKA activation, by inducing a complex transcriptional program, leads to cancer survival in nutrient stress, a typical feature of developing tumor. These transcriptional data, identifying this important role of PKA, will be useful to identify novel target in cancer therapy. PMID:27486565

  19. Electrical methods (VES and ERT) for identifying, mapping and monitoring different saline domains in a coastal plain region (Alt Empordà, Northern Spain)

    Science.gov (United States)

    Zarroca, Mario; Bach, Joan; Linares, Rogelio; Pellicer, Xavier M.

    2011-10-01

    SummaryThe spatial variability through time of the degree of salinity of soils and groundwater is a major issue concerning the sustainable management of water resources. The problem is accentuated in coastal plain areas where saline bodies of different origin coexist. We present an extensive geoelectrical resistivity dataset collected in the Alt Empordà clastic coastal aquifer system (NE Spain) integrating the results of field campaigns undertaken within a period of more than two decades. The dataset is unique in the literature and comprises highly valuable information for the investigation of saline domains. The joint application of Vertical Electrical Sounding (VES) and Electrical Resistivity Tomography (ERT) methods allowed the identification of saline domains and monitoring their evolution through time. Geophysical data gathered during field campaigns in 1982, 2002 and 2010 were calibrated and interpreted on the basis of soil and groundwater physico-chemical analyses and hydrogeological, stratigraphic and geomorphological data. The results illustrate the potential of electrical resistivity methods at differentiating saline domains in coastal aquifer areas and at modelling their configuration and evolution. Although the VES data processing allows solving the one-dimensional resistivity structure of the subsurface, the inversion imposes a 1D layered model, thus interpretation of two-dimensional structures is subject to the interpolation between discrete measures. In contrast, ERT data offer a continuous 2D-image of the resistivity distribution, both laterally and in depth. Given that the bulk resistivity of the medium is extremely sensitive to salt content, the ERT profiles permitted identifying and determining the geometry of hyper-saline areas (characterized by resistivities of less than 5 Ω m). The study demonstrates the efficiency of the electrical methods to map subsurface conductive zones and illustrates how the accurate knowledge of the hydrogeological

  20. Dioxin exerts anti-estrogenic actions in a novel dioxin-responsive telomerase-immortalized epithelial cell line of the porcine oviduct (TERT-OPEC).

    Science.gov (United States)

    Hombach-Klonisch, Sabine; Pocar, Paola; Kauffold, Johannes; Klonisch, Thomas

    2006-04-01

    Oviduct epithelial cells are important for the nourishment and survival of ovulated oocytes and early embryos, and they respond to the steroid hormones estrogen and progesterone. Endocrine-disrupting polyhalogenated aromatic hydrocarbons (PHAH) are environmental toxins that act in part through the ligand-activated transcription factor arylhydrocarbon receptor (AhR; dioxin receptor), and exposure to PHAH has been shown to decrease fertility. To investigate effects of PHAHs on the oviduct epithelium as a potential target tissue of dioxin-type endocrine disruptors, we have established a novel telomerase-immortalized oviduct porcine epithelial cell line (TERT-OPEC). TERT-OPEC exhibited active telomerase and the immunoreactive epithelial marker cytokeratin but lacked the stromal marker vimentin. TERT-OPEC contained functional estrogen receptor (ER)-alpha and AhR, as determined by the detection of ER-alpha- and AhR-specific target molecules. Treatment of TERT-OPEC with the AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in a significant increase in the production of the cytochrome P-450 microsomal enzyme CYP1A1. Activated AhR caused a downregulation of ER nuclear protein fraction and significantly decreased ER-signaling in TERT-OPEC as determined by ERE-luciferase transient transfection assays. In summary, the TCDD-induced and AhR-mediated anti-estrogenic responses by TERT-OPEC suggest that PHAH affect the predominantly estrogen-dependent differentiation of the oviduct epithelium within the fallopian tube. This action then alters the local endocrine milieu, potentially resulting in a largely unexplored cause of impaired embryonic development and female infertility. PMID:16431846

  1. Expression of progesterone receptor membrane component-2 within the immature rat ovary and its role in regulating mitosis and apoptosis of spontaneously immortalized granulosa cells.

    Science.gov (United States)

    Griffin, Daniel; Liu, Xiufang; Pru, Cindy; Pru, James K; Peluso, John J

    2014-08-01

    Progesterone receptor membrane component 2 (Pgrmc2) mRNA was detected in the immature rat ovary. By 48 h after eCG, Pgrmc2 mRNA levels decreased by 40% and were maintained at 48 h post-hCG. Immunohistochemical studies detected PGRMC2 in oocytes and ovarian surface epithelial, interstitial, thecal, granulosa, and luteal cells. PGRMC2 was also present in spontaneously immortalized granulosa cells, localizing to the cytoplasm of interphase cells and apparently to the mitotic spindle of cells in metaphase. Interestingly, PGRMC2 levels appeared to decrease during the G1 stage of the cell cycle. Moreover, overexpression of PGRMC2 suppressed entry into the cell cycle, possibly by binding the p58 form of cyclin dependent kinase 11b. Conversely, Pgrmc2 small interfering RNA (siRNA) treatment increased the percentage of cells in G1 and M stage but did not increase the number of cells, which was likely due to an increase in apoptosis. Depleting PGRMC2 did not inhibit cellular (3)H-progesterone binding, but attenuated the ability of progesterone to suppress mitosis and apoptosis. Taken together these studies suggest that PGRMC2 affects granulosa cell mitosis by acting at two specific stages of the cell cycle. First, PGRMC2 regulates the progression from the G0 into the G1 stage of the cell cycle. Second, PGRMC2 appears to localize to the mitotic spindle, where it likely promotes the final stages of mitosis. Finally, siRNA knockdown studies indicate that PGRMC2 is required for progesterone to slow the rate of granulosa cell mitosis and apoptosis. These findings support a role for PGRMC2 in ovarian follicle development.

  2. Wnt activation of immortalized brain endothelial cells as a tool for generating a standardized model of the blood brain barrier in vitro.

    Directory of Open Access Journals (Sweden)

    Roberta Paolinelli

    Full Text Available Reproducing the characteristics and the functional responses of the blood-brain barrier (BBB in vitro represents an important task for the research community, and would be a critical biotechnological breakthrough. Pharmaceutical and biotechnology industries provide strong demand for inexpensive and easy-to-handle in vitro BBB models to screen novel drug candidates. Recently, it was shown that canonical Wnt signaling is responsible for the induction of the BBB properties in the neonatal brain microvasculature in vivo. In the present study, following on from earlier observations, we have developed a novel model of the BBB in vitro that may be suitable for large scale screening assays. This model is based on immortalized endothelial cell lines derived from murine and human brain, with no need for co-culture with astrocytes. To maintain the BBB endothelial cell properties, the cell lines are cultured in the presence of Wnt3a or drugs that stabilize β-catenin, or they are infected with a transcriptionally active form of β-catenin. Upon these treatments, the cell lines maintain expression of BBB-specific markers, which results in elevated transendothelial electrical resistance and reduced cell permeability. Importantly, these properties are retained for several passages in culture, and they can be reproduced and maintained in different laboratories over time. We conclude that the brain-derived endothelial cell lines that we have investigated gain their specialized characteristics upon activation of the canonical Wnt pathway. This model may be thus suitable to test the BBB permeability to chemicals or large molecular weight proteins, transmigration of inflammatory cells, treatments with cytokines, and genetic manipulation.

  3. Leflunomide or A77 1726 protect from acetaminophen-induced cell injury through inhibition of JNK-mediated mitochondrial permeability transition in immortalized human hepatocytes

    International Nuclear Information System (INIS)

    Leflunomide, a disease-modifying anti-rheumatic drug, protects against T-cell-mediated liver injury by poorly understood mechanisms. The active metabolite of leflunomide, A77 1726 (teriflunomide) has been shown to inhibit stress-activated protein kinases (JNK pathway), which are key regulators of mitochondria-mediated cell death. Therefore, we hypothesized that leflunomide may protect from drugs that induce the mitochondrial permeability transition (mPT) by blocking the JNK signaling pathway. To this end, we exposed cultured immortalized human hepatocytes (HC-04) to the standard protoxicant drug acetaminophen (APAP), which induces CsA-sensitive mPT-mediated cell death. We determined the effects of leflunomide on the extent of APAP-induced hepatocyte injury and the upstream JNK-mediated mitochondrial signaling pathways. We found that leflunomide or A77 1726 concentration-dependently protected hepatocytes from APAP (1 mM)-induced mitochondrial permeabilization and lethal cell injury. This was not due to proximal inhibition of CYP-catalyzed APAP bioactivation to its thiol-reactive metabolite. Instead, we demonstrate that leflunomide (20 μM) inhibited the APAP-induced early (3 h) activation (phosphorylation) of JNK1/2, thus inhibiting phosphorylation of the anti-apoptotic protein Bcl-2 and preventing P-Bcl-2-mediated induction of the mPT. This greatly attenuated mitochondrial cytochrome c release, which we used as a marker for mitochondrial permeabilization. The specific JNK2 inhibitor SP600125 similarly protected from APAP-induced cell death. In conclusion, these findings are consistent with our hypothesis that leflunomide protects from protoxicant-induced hepatocyte injury by inhibiting JNK signaling and preventing mPT induction

  4. Palmitate alters the rhythmic expression of molecular clock genes and orexigenic neuropeptide Y mRNA levels within immortalized, hypothalamic neurons.

    Science.gov (United States)

    Fick, Laura J; Fick, Gordon H; Belsham, Denise D

    2011-09-30

    The control of energy homeostasis within the hypothalamus is under the regulated control of homeostatic hormones, nutrients and the expression of neuropeptides that alter feeding behavior. Elevated levels of palmitate, a predominant saturated fatty acid in diet and fatty acid biosynthesis, alter cellular function. For instance, a key mechanism involved in the development of insulin resistance is lipotoxicity, through increased circulating saturated fatty acids. Although many studies have begun to determine the underlying mechanisms of lipotoxicity in peripheral tissues, little is known about the effects of excess lipids in the brain. To determine these mechanisms we used an immortalized, clonal, hypothalamic cell line, mHypoE-44, to demonstrate that palmitate directly alters the expression of molecular clock components, by increasing Bmal1 and Clock, or by decreasing Per2, and Rev-erbα, their mRNA levels and altering their rhythmic period within individual neurons. We found that these neurons endogenously express the orexigenic neuropeptides NPY and AgRP, thus we determined that palmitate administration alters the mRNA expression of these neuropeptides as well. Palmitate treatment causes a significant increase in NPY mRNA levels and significantly alters the phase of rhythmic expression. We explored the link between AMPK and the expression of neuropeptide Y using the AMPK inhibitor compound C and the AMP analog AICAR. AMPK inhibition decreased NPY mRNA. AICAR also elevated basal NPY, but prevented the palmitate-mediated increase in NPY mRNA levels. We postulate that this palmitate-mediated increase in NPY and AgRP synthesis may initiate a detrimental positive feedback loop leading to increased energy consumption.

  5. Ways to live history. Or philosophy, culture, and architecture in the origins of the museum Altes in Berlín Formas de habitar la historia. O la filosofía, la cultura y la arquitectura en la fundación del Museo Altes de Berlín Modos de habitar a história ou Filosofia, cultura e arquitetura na fundação do Altes Museum de Berlim

    Directory of Open Access Journals (Sweden)

    Fabiano Lemos

    2011-01-01

    Full Text Available From the beginnings of what we now know as our modernity, man has been surprised with his own finitude. The 18th and 19th  century bourgeois needed to formulate complex ways of preserving the past and of linking with it. In the philosophes’ circle, time concept starts to double itself in the idea of origin, that, for them, had become opaque. We just need to think of the broad-range process of structuring museums and restructuring natural history collections in cities such as Paris and Berlin, around the turn to the 19th century, so that we can be convinced that the surprise with that origin that one cannot recognize anymore, that becomes object of popular and scientific interest, leads each and all of the decisions in this process. Museum is just one of the institutions in which man, through a complex series of idealizations of space, show himself the spectacle of a lost time and, thus, of a culture whose educational thrive can only be understood by associating to these institutions. Our task is to investigate – and the case study of the grounding of the Altes Museum in Berlin, between 1822 and 1830, will perform this concretely – which educational policy made the emergence of this new ideological model possible, and , on the opposite way, which conceptual elaborations confirmed or legitimated the new pragmatic topography of time in modernity within the institution that had as aim, precisely, articulate and administrate past and memory. Desde los albores de la modernidad tal como la entendemos hoy en día, el hombre se espanta por su finitud. El burgués de los siglos XVIII y XIX tuvo que crear mecanismos complejos para la preservación del pasado y su relación con él. En el círculo de philosophes, la noción del tiempo comienza a replicarse en la idea de origen, que para ellos se convirtió en opaca. Basta pensar en el amplio

  6. The Impact of 10 weeks of Aerobic Exercise and Supplementation of Green Tea on Lipid Profile, Insulin Resistance and Liver Enzymes (GGT, ALT, AST) in Obese Diabetic Women (type 2)

    OpenAIRE

    M Izadi Ghahfarokhi; M Mogharnasi; M Faramarzi

    2015-01-01

    Background & aim: Physical training accompanied with herbal supplement consumption is one of the proposed methods for controlling obesity and its complications, such as diabetes, insulin resistance and inflammation of the liver. The purpose of this study was to evaluate the effect of 10 weeks of aerobic exercise and supplementation of green tea on lipid profile, insulin resistance and liver enzymes (GGT, ALT, AST) in obese diabetic women (type 2). Materials and Methods: A total of 46 di...

  7. Uji Klinis Pendahuluan Pengaruh Pemberian Kapsul Kombinasi Ekstrak Herba Sambiloto (Andrographis paniculata (Burm.f.) Nees) dan Daun Salam (Syzygium polyanthum (Wight) Walp.) Terhadap Kadar ALT dan AST pada Pasien Dislipidemia

    OpenAIRE

    Andriani, Desi

    2015-01-01

    The liver is central organ of drug metabolism. Damage of liver cell can be marked from several parameters, such as from increased levels of ALT and AST. The results of pre-clinical research to extract the bitter herbs and bay leaves indicate that the extract is not toxic to the liver and having effect of the decreased cholesterol and triglyceride levels synergistically. The bitter herbs extract more effective on the decrease cholesterol levels, whereas the bay leaf extract more effective on t...

  8. PARÁMETROS BIOQUÍMICOS ENZIMÁTICOS (ALT, AST, ALP, Γ-GT, LDH) EN NIÑOS CON LEUCEMIA LINFOBLÁSTICA AGUDA ANTES DEL TRATAMIENTO ANTINEOPLÁSICO

    OpenAIRE

    Jeél Moya S; Liz Pio D

    2015-01-01

    Objective: To determine the enzymatic biochemical parameters (glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), alkaline phosphatase (ALP), gamma glutamyltransferase (γ-GT), and lactate dehydrogenase (LDH)) in children with acute lymphoblastic leukemia (ALL) before cancer treatment. Material and Methods: A prospective experimental, observational, cross-sectional study was conducted in 30 children between 2 and 15 years old, from several Neoplastic Centers in Lim...

  9. PARÁMETROS BIOQUÍMICOS ENZIMÁTICOS (ALT, AST, ALP, Γ-GT, LDH EN NIÑOS CON LEUCEMIA LINFOBLÁSTICA AGUDA ANTES DEL TRATAMIENTO ANTINEOPLÁSICO

    Directory of Open Access Journals (Sweden)

    Jeél Moya S

    2015-12-01

    Full Text Available Objective: To determine the enzymatic biochemical parameters (glutamic pyruvic transaminase (ALT, glutamic oxaloacetic transaminase (AST, alkaline phosphatase (ALP, gamma glutamyltransferase (γ-GT, and lactate dehydrogenase (LDH in children with acute lymphoblastic leukemia (ALL before cancer treatment. Material and Methods: A prospective experimental, observational, cross-sectional study was conducted in 30 children between 2 and 15 years old, from several Neoplastic Centers in Lima. Blood collection was performed in BD red cap Vacutainer tubes, processed in the semi-automated analyzer BIOTEC® EMP-168, with Wiener Lab Group enzyme reagents under the modified method Szaaz and UV-Optimized by IFCC, SSCC and SFBC. Finally, coding and tabulation was performed. Results: 60% were boys and 46.7% are between the ages of 2-6 years. Serum levels of AST were increased by 33.3% in boys and 50% in girls. Serum ALT values were increased in 33.3% of boys and 41.7% of girls; only 25% of girls showed increased levels of γ-GT values; ALP was increased in 44.4% of boys and 66.7% of girls. Moreover LDH levels were increased in 55.6% of boys and 41.7% of girls. Conclusions: The enzymatic tests LDH, AST, ALT and ALP are increased in children with ALL compared to normal values due to tumor lysis syndrome characterized by electrolyte abnormalities, and as a result of the massive destruction of tumor cells and rapid release of large amounts of intracellular elements.

  10. DFM in practice: results of a three way partnership between a leading fabless design house, foundry, and EDA company to implement alternating-phase shift mask (Alt-PSM) on a 90-nm FPGA chip

    Science.gov (United States)

    Yu, Chun-Chi; Shieh, Ming-Feng; Liu, Erick; Lin, Benjamin; Lin, Henry; Chacko, Manoj; Li, Xiaoyang; Lei, Wen-Kang; Ho, Jonathan; Wu, Xin

    2005-05-01

    At the sub 90nm nodes, resolution enhancement techniques (RETs) such as optical proximity correction (OPC), phase-shifting masks (PSM), sub-resolution assist features (SRAF) have become essential steps in the post-physical verification 'Mask Synthesis' process and a key component of design for manufacturing (DFM). Several studies have been conducted and the results have been published on the implication and application of the different types of RETs on mask printability and costs. More specifically, double-exposure-based, dark-field, alternating PSM (Alt-PSM) technology has received lot of attention with respect to the mask manufacturing challenges and its implementation into a production flow, despite its yield and critical dimension (CD) control superiority. Implementation of Alt-PSM generally requires phase compliance rules and proper phase topology in the layout and this has been successful for the technology node with these rules implemented. However, this may not be true for a matured, production process technology, in this case 90 nm. Especially, in the foundry-fabless business model where the foundry provides a standard set of design rules to its customers for a given process technology, and where not all the foundry customers require Alt-PSM in their tapeout flow. What follows is an in-depth review of the DFM challenges to each partner faced, its effect on the tapeout flow, and how design, manufacturing, and EDA teams worked together to resolve phase conflicts, tapeout the chip, and finally verify the silicon results in production.

  11. Mianyang healthy examination crowd serum ALT and gender and age relations discussed%绵阳市健康体检人群血清ALT与性别年龄关系探讨

    Institute of Scientific and Technical Information of China (English)

    胡春枝; 陈雪梅; 贺小燕

    2015-01-01

    目的:探讨绵阳市人群血清丙氨基转移酶(ALT)水平与性别年龄关系,为临床运用及本地区ALT水平的制定提供参考资料。方法:测定绵阳市10916例健康体检者血清ALT的值,并对不同性别、年龄人群血清ALT 结果进行统计学分析。结果:绵阳市受检人群中男性血清ALT均值水平高于女性,不同性别间有显著差异(P0.05),其余各组均有显著差异(P0.05), the rest of the Group has significant differences (P<0.001).Conclusion:Sex and age is one of the factors affecting serum ALT levels, its factors in clinical diagnosis should be considered, reference values for serum. ALT should be developed under different geographical, age and gender.

  12. Novel poly(triphenylamine-alt-fluorene) with asymmetric hexaphenylbenzene and pyrene moieties: synthesis, fluorescence, flexible near-infrared electrochromic devices and theoretical investigation

    KAUST Repository

    Wang, Po-I.

    2016-01-13

    © The Royal Society of Chemistry 2016. In this study, a new triphenylamine-alt-fluorene conjugated copolymer, HPBPYFL6, with hexaphenylbenzene (HPB) and pyrene as asymmetrical pendant groups was synthesized via Suzuki coupling polymerization. The conjugated polymer had a weight-average molecular weight of 5.8 × 104 g mol-1 with a polydispersity index of 2.5 characterized by gel permeation chromatography (GPC). HPBPYFL6 showed good solubility in common organic solvents such as NMP, THF, toluene and dichloromethane at 25°C. In addition, HPBPYFL6 possessed a high glass transition temperature of 260°C and a 10% weight-loss temperature of 503°C in nitrogen. HPBPYFL6 bearing a pyrene moiety had a solvatochromic fluorescence shift from a green to an orange emission as the polarity of the solvent increased. Cyclic voltammetry of HPBPYFL6 films cast onto indium-tin oxide-coated glass (ITO-glass) exhibited two oxidation redox couples at an E1/2 value of 0.82 and 1.17 V versus Ag/Ag+ in an acetonitrile solution. The HPBPYFL6 film on graphene-coated PET had an E1/2 value of 0.24 and 1.12 V. Conjugated polymer films exhibited reversible electrochromic behaviour with a colour change from pale yellow to deep blue upon electrochemical oxidation and high absorbance in the near-infrared (NIR) region. The switching and bleaching times were 5.16 s and 3.12 s for 1231 nm and were 3.30 s and 3.74 s for 1030 nm of HPBPYFL6 on ITO-glass. The strong NIR electrochromic absorbance of HPBPYFL6 was attributed to intervalence charge transfer by the incorporation of the HPB moiety. This phenomenon was confirmed by chemical oxidation as the oxidant contents increased in the solution state. Furthermore, the electrochromic mechanism was interpreted by DFT calculation and the simulated NIR electrochromic spectra of model compound HPBPYFL are in good agreement with the experimental data.

  13. La aportación de Étienne Gilson al problema de la inmortalidad del alma humana en Cayetano / The Contribution of Étienne Gilson to the Problem of the Immortality of the Human Soul in Cajetan

    OpenAIRE

    Ceferino P. D. Muñoz

    2013-01-01

    In his article the author reviews Cajetan’s different positions on the prob-lem of the immortality of the human soul, and investigates possible reasons which led the Cardinal to dissent with the position of Thomas Aquinas. For this purpose, he invokes selected interpretations of distinguished scholars, with special reference to the approach of Étienne Gilson. Against the back-ground of his analyses the authors attempts to give a synthesis which, as he hopes, can become a modest contribution t...

  14. Effect of allergen-specific immunotherapy with purified Alt a1 on AMP responsiveness, exhaled nitric oxide and exhaled breath condensate pH: a randomized double blind study

    Directory of Open Access Journals (Sweden)

    Prieto Luis

    2010-09-01

    Full Text Available Abstract Background Little information is available on the effect of allergen-specific immunotherapy on airway responsiveness and markers in exhaled air. The aims of this study were to assess the safety of immunotherapy with purified natural Alt a1 and its effect on airway responsiveness to direct and indirect bronchoconstrictor agents and markers in exhaled air. Methods This was a randomized double-blind trial. Subjects with allergic rhinitis with or without mild/moderate asthma sensitized to A alternata and who also had a positive skin prick test to Alt a1 were randomized to treatment with placebo (n = 18 or purified natural Alt a1 (n = 22 subcutaneously for 12 months. Bronchial responsiveness to adenosine 5'-monophosphate (AMP and methacholine, exhaled nitric oxide (ENO, exhaled breath condensate (EBC pH, and serum Alt a1-specific IgG4 antibodies were measured at baseline and after 6 and 12 months of treatment. Local and systemic adverse events were also registered. Results The mean (95% CI allergen-specific IgG4 value for the active treatment group increased from 0.07 μg/mL (0.03-0.11 at baseline to 1.21 μg/mL (0.69-1.73, P 4 value increased nonsignificantly from 0.09 μg/mL (0.06-0.12 at baseline to 0.13 μg/mL (0.07-0.18 at 6 months and to 0.11 μg/mL (0.07-0.15 at 12 months of treatment. Changes in the active treatment group were significantly higher than in the placebo group both at 6 months (P Conclusion Although allergen-specific immunotherapy with purified natural Alt a1 is well tolerated and induces an allergen-specific IgG4 response, treatment is not associated with changes in AMP or methacholine responsiveness or with significant improvements in markers of inflammation in exhaled air. These findings suggest dissociation between the immunotherapy-induced increase in IgG4 levels and its effect on airway responsiveness and inflammation.

  15. Zile Elbaşoğlu Camii’nin Sıvalar Altında Kalan Gizemi The Mystery Of The Zile-Elbaşoğlu Mosque Remains Under Plasters

    Directory of Open Access Journals (Sweden)

    Ali Murat AKTEMUR

    2013-09-01

    Full Text Available Elbaşoğlu Mosque was built in 1801 by Ahmet Aga, clean-cutstone architecture, square, rectangular with remarkable inscriptionsElbaşoğlu Mosque is one of the local mosque, wood-backed and woodenceilings. Until 2007, the walls and the ceiling, and even the altar,wooden support, wood columns, wooden gallery, galleries, in short, allthe wooden elements of the mosque was covered with oil on sweet-limeplaster. In 2007, during the repair of the roof of a simple chance, withplaster falling due to the flowing water under the pen-and-repair workon the emergence of ornaments and wooden decorations samples, thenstopped cleaning and scraper operations in the administration of theGeneral Directorate of Foundations in the interior of the mosque penrichsamples of work, with examples of wooden decorative plaster underthe mystery was revealed.Cover at the top of the walls combined with Harim calligraphy ona black background with spots, including a concave border of the beltframed verse was written. Verse generation raised on the corners of theceiling moldings created crash of beads, triangle, octagon in the middleof a field, and thus created the split surfaces. Located in the middle ofthe octagon octagon-shaped belly, finished with carving technique,baroque decorated with floral motifs. the four corners of the triangularroof panels are decorated with reliefs excess plastic plant. Pen-workdecoration floral motifs on the walls, gallery, pulpits, pillars, such asthe carved wooden elements fall floral and geometric motifs are carvedin the mosque offers a wealth of eye-catching as almost free space left.Made in 1801, in the early years of the Republic, the region'sunique sweet-lime paint on plaster taken off this rich decoration, woodart and pen-work ornamentation Turkey offers one of the richest. Tokat Zile’de Elbaşoğlu Ahmet Ağa tarafından 1801 yılında inşa ettirilen, düzgün kesme taş mimarisi, kitabeleri ile dikkat çeken, kareye yakın dikd

  16. 西安地区健康人群ALT与AST参考区间的初步探讨%Study the Reference Intervals for the Hepatic Marker Enzymes ALT and AST

    Institute of Scientific and Technical Information of China (English)

    周铁成; 张莹; 童开; 岳乔红; 郝晓柯

    2011-01-01

    目的 建立西安地区健康人群血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)的参考区间.方法 参照IFCC多中心酶学研究参考人群筛选标准,募集18~79岁健康参考人群1 098人,其中男性506人和女性592人,分别用和光试剂检测系统、加入磷酸吡哆醛的罗氏试剂检测系统和不加磷酸吡哆醛的罗氏试剂检测系统建立西安地区健康人群酶活性参考区间.结果 三个系统间检测结果存在明显差异(P<0.01),各系统间男性和女性结果存在差异.ALT和AST需要按性别划分参考区间.不加磷酸吡哆醛的罗氏试剂检测系统ALT-1:7.46~51.34 U/L(女),9.09~71.06 U/L(男);AST-1:11.89~40.49 U/L(女),13.6~40.52 U/L(男).加入磷酸吡哆醛的罗氏试剂检测系统ALT-P:10.24~57.06 U/L(女),11.02~84.00 U/L(男);AST-P:13.55~50.14 U/L(女),15.3~53.42 U/L(男).和光试剂检测系统ALT:6.41~41.73 U/L(女),7.21~67.77 U/L(男);AST:9.41~40.64 U/L(女),12.1~41.11 U/L(男).结论 西安地区人群ALT和AST三个系统间检测结果的参考区间上限较目前临床所用参考区间较高,且各个检测系统间结果存在较大差异.罗氏加入磷酸吡哆醛试剂的参考范围高于不加磷酸吡哆醛试剂的参考范围,加入磷酸吡哆醛试剂的参考范围比不加磷酸吡哆醛试剂的参考范围高15%~20%.但不加磷酸吡哆醛试剂的参考范围高于和光试剂(不加磷酸吡哆醛)检测结果的参考范围,不加磷酸吡哆醛试剂的参考范围比和光试剂(不加磷酸吡哆醛)检测结果的参考范围约高10%.而和光试剂(不加磷酸吡哆醛)检测结果高于目前临床所用的参考范围.%Objective Study the reference intervals for the hepatic marker enzymes ALT and AST in Xi'an. Methods Following multi-center study of IFCC enzyme reference population screening criteria. Blood specimens were collected from 1 098 healthy individuals aged 18-79.including 506 males and 592

  17. The “Tiantai Mountain Performing Skills” and Immortal Taoism Drama%“天台山伎”与神仙道化剧

    Institute of Scientific and Technical Information of China (English)

    高莹; 张子健

    2015-01-01

    On the basis of the monarch preferences in the Southern Qi Dynasty,the “Tiantai Mountain Performing Skills” was created by Zheng Yitai,a minister in charge of royal music and fete. “Tiantai Mountain Tour” was written by Sun Chuo of the Eastern Jin Dynasty when he was enjoying Tiantai pic-tures,not when visiting the sceneries. One of the detailed descriptions was adapted to the core of the“Tiantai Mountain Performing Skills” by Zheng Yitai. It was later named “Meitai Theater”. “Tiantai Moun-tain Performing Skills” was related to the Taoist and Taoism;however,it was not the religious show,but a design of the role of the dress. As an immortal Taoism drama,it has had a far-reaching influence.%太乐令依据君主喜好,随时有所创制,南齐“天台山伎”即因太乐令郑义泰影响而生。《游天台山赋》为剧目蓝本,此赋由东晋高士孙绰赏读天台山图画写成,并非当时游历所得。赋中的细节描写“践莓苔之滑石,搏壁立之翠屏”,被太乐令郑义泰等改编为“天台山伎”的核心情节。后世因此又称“莓苔戏”。“天台山伎”的生成固然与道士、道教有关,但并非宗教意义的仪式展现,而是设计角色的装扮表演。作为神仙道化剧,其影响深远。

  18. Triggering of toll-like receptors 2 and 4 by Aspergillus fumigatus conidia in immortalized human corneal epithelial cells to induce inflammatory cytokines

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jie; WU Xin-yi

    2008-01-01

    Background Cornea epithelial cells play early and crucial roles in the initiation of ocular surface responses to pathogens.Participation of toll-like receptor(TLR)2 and TLR4,which are major forms of fungi receptors,may be involved in Aspergillus fumigatus induced immune responses.The obiective of the present study was to examine whether inactive Aspergillus fumigatus conidia induce NF-κB activation and production of proinflammaory cytokines,and whether the expression of TLR2 and TLR4 were amplified by conidia in cultured immortalized human corneal epithelial cells (THCEs).This may contribute to our knowledge of the mechanism by which the host cornea can successfully defend against invasive fungi.Methods Aspergillus fumigatus conidia were used to challenge THCE cells.THCE cells were harvested after 0.5,1,2or 4 hours incubation.Real-time quantitative PCR was performed to determine the expression of TLR2,TLR4,TNF-α and IL-8.Western blotting was performed to determine the expression of NF-κB.Enzyme-linked immunosorbent assay (EUSA)was performed to determine the expression of TNF-α and IL-8.And the release of TNF-α and IL-8 in the cell supematant were also assessed by ELISA with or without pretreatment with TLR2 and TLR4 neutralizing antibodies.Results Aspergillus fumigatus conidia elicited the expression of TLR2,TLR4,TNF-α and IL-8 mRNA in THCEs.Exposure of THCE cells to Aspergillus fumigatus conidia resulted in NF-κB activation,which increased at 30 minutes (increased from 11.35±2.74 in the controls to 19.12±3.48,P<0.05)and thereafter increased steadily up to 4 hours after challenge(P<0.01).Concomitant with NF-κB acfivation,secretion of TNF-α and IL-8 in conidia-challenged cells was increased in a time-dependent manner.Incubation of THCE cells with TLR2 antibody or TLR4 antibody before conidia challenge resulted in jnhibifion of conidia-induced TNF-α and IL-8 secretion(P<0.05),TLR2 antibody and TLR4 antibody together significantly increased

  19. Telomere,telomerase,cell of immortalization and aging%端粒、端粒酶与细胞衰老及永生化

    Institute of Scientific and Technical Information of China (English)

    滕勇; 胡蕴玉; 关玉成

    2008-01-01

    正常细胞体外培养时,表现为有限生长特性,经一定的细胞倍增次数后,失去了对促分裂因子刺激的反应,不可逆地失去增殖能力而停止分裂,细胞开始衰老的历程.目前认为染色体末端(端粒)的缺失会使细胞逐渐失去增殖能力,导致细胞的衰老和死亡.人端粒酶催化亚单位(hTERT)可以激活端粒酶的活性,延长染色体末端DNA,维持基因组的稳定.端粒、端粒酶、hTERT的发现为细胞衰老的研究提供了新的思路,同时也应用于永生化细胞系的建立,特别是在组织工程种子细胞生物性能研究和细胞库的建立中将发挥重要作用.%Normal cells have limited proliferation ability.After certain cycles of proliferation,they will lose the response ability to growth factors and finally cease division and start the course of aging. In current opinion,lacking of the terminal end of a chromosome(telomere)is the cause for cells to loss the proliferation ability and leads cells to aging and death.The human telomerase catalytic subunit 1(hTERT)can activate telomemse which prolong DNAs of the terminal end of chmmosome and help cells gain genomic stabilization.The discoveries of telomere,telomerase and hTERT provide new idea for studying of cell aging and the findings are also applied in the establishment of immortal cell line. Also they may play an important role in the studv of biological feature of seed cell in tissue engineering and the establishment of cell bank.

  20. Transplantation of Immortalized CD34+ and CD34- Adipose-Derived Stem Cells Improve Cardiac Function and Mitigate Systemic Pro-Inflammatory Responses.

    Directory of Open Access Journals (Sweden)

    Jong-Ho Kim

    Full Text Available Adipose-derived stem cells (ADSCs have the potential to differentiate into various cell lineages and they are easily obtainable from patients, which makes them a promising candidate for cell therapy. However, a drawback is their limited life span during in vitro culture. Therefore, hTERT-immortalized CD34+ and CD34- mouse ADSC lines (mADSCshTERT tagged with GFP were established. We evaluated the proliferation capacity, multi-differentiation potential, and secretory profiles of CD34+ and CD34- mADSCshTERT in vitro, as well as their effects on cardiac function and systemic inflammation following transplantation into a rat model of acute myocardial infarction (AMI to assess whether these cells could be used as a novel cell source for regeneration therapy in the cardiovascular field. CD34+ and CD34- mADSCshTERT demonstrated phenotypic characteristics and multi-differentiation potentials similar to those of primary mADSCs. CD34+ mADSCshTERT exhibited a higher proliferation ability compared to CD34- mADSCshTERT, whereas CD34- mADSCshTERT showed a higher osteogenic differentiation potential compared to CD34+ mADSCshTERT. Primary mADSCs, CD34+, and CD34- mADSCshTERT primarily secreted EGF, TGF-β1, IGF-1, IGF-2, MCP-1, and HGFR. CD34+ mADSCshTERT had higher secretion of VEGF and SDF-1 compared to CD34- mADSCshTERT. IL-6 secretion was severely reduced in both CD34+ and CD34- mADSCshTERT compared to primary mADSCs. Transplantation of CD34+ and CD34- mADSCshTERT significantly improved the left ventricular ejection fraction and reduced infarct size compared to AMI-induced rats after 28 days. At 28 days after transplantation, engraftment of CD34+ and CD34- mADSCshTERT was confirmed by positive Y chromosome staining, and differentiation of CD34+ and CD34- mADSCshTERT into endothelial cells was found in the infarcted myocardium. Significant decreases were observed in circulating IL-6 levels in CD34+ and CD34- mADSCshTERT groups compared to the AMI

  1. Aloe vera: Plant of Immortality

    OpenAIRE

    Sikarwar Mukesh S.; Patil M B; Bhat Vishnu; Sharma Shalini

    2010-01-01

    The Egyptians called Aloe the “Plant of Immortality” because it can live and even bloom without soil. Aloe has been used medicinally since at least the first century C.E. and continues to be used extensively worldwide.

  2. Aloe vera: Plant of Immortality

    Directory of Open Access Journals (Sweden)

    Sikarwar Mukesh. S.

    2010-02-01

    Full Text Available The Egyptians called Aloe the “Plant of Immortality” because it can live and even bloom without soil. Aloe has been used medicinally since at least the first century C.E. and continues to be used extensively worldwide.

  3. Heat reveals faults

    Energy Technology Data Exchange (ETDEWEB)

    Weinreich, Bernhard [Solarschmiede GmbH, Muenchen (Germany). Engineering Dept.

    2010-07-01

    Gremlins cannot hide from the all-revealing view of a thermographic camera, whereby it makes no difference whether it is a roof-mounted system or a megawatt-sized farm. Just as diverse are the range of faults that, with the growing level of expertise, can now be detected and differentiated with even greater detail. (orig.)

  4. Android Emotions Revealed

    DEFF Research Database (Denmark)

    Vlachos, Evgenios; Schärfe, Henrik

    2012-01-01

    in which case an android robot like the Geminoid|DK –a duplicate of an Original person- reveals emotions convincingly; when following an empirical perspective, or when following a theoretical one. The methodology includes the processes of acquiring the empirical data, and gathering feedback on them. Our...

  5. Efeitos da farinha de folhas de mandioca sobre a atividade das enzimas AST, ALT, FA e lipídios hepáticos de ratos Wistar Effects of cassava leaves flour on the AST, ALT, ALP enzymes activity and hepatic lipids of Wistar rats

    Directory of Open Access Journals (Sweden)

    Daniela Séfora de Melo

    2008-12-01

    Full Text Available Folhas de mandioca possuem substâncias como ligninas e saponinas que podem apresentar efeito hipolipidêmico. Todavia, um estudo recente relatou aumento no peso do fígado de ratos alimentados com dietas contendo farinha de folhas de mandioca (FFM - Manihot esculenta Crantz cv. Cacao, tornando-se necessário um estudo mais aprofundado dos efeitos desta farinha sobre os parâmetros hepáticos. Para este estudo, um ensaio biológico com 32 ratos machos Wistar foi conduzido por um período de 7 semanas, sendo os tratamentos: dieta controle e dietas contendo 5, 10 e 15% de FFM. As dietas contendo FFM não apresentaram efeitos sobre as atividades das enzimas Aspartato Aminotransferase (AST e Fosfatase Alcalina (FA, mas aumentaram significativamente a atividade da enzima alanina aminotransferase (ALT. O estudo histopatológico revelou vacuolização do citoplasma dos hepatócitos para todos os grupos. No entanto, a freqüência de animais com vacuolização acentuada foi superior nos grupos que receberam dietas com FFM, apresentando também maiores teores de lipídios e colesterol total hepáticos e maior relação peso fígado/peso corporal. Estes resultados indicam que os antinutrientes presentes nas folhas de mandioca, como taninos, cianeto e saponinas, podem ser responsáveis pela redução da função hepática nos animais alimentados com FFM.Cassava leaves contain substances such as lignins and saponins that can present the hypolipidemic effect. However, a recent study has reported an increase in liver weight of rats fed diet containing cassava leaves flour (CLF - Manihot esculenta Crantz cv. Cacao. Thus, a further study of the effect of this flour on the hepatic parameters is necessary. For the development of this study, a biological assay with 32 male Wistar rats was conducted for a period of 7 weeks with the following treatments: control diet and diets containing 5, 10, and 15% of CLF. The diets containing CLF showed no effects on the

  6. La transformación de los asentamientos en el litoral turístico catalán: análisis cartográfico y estadístico del Alt Empordà

    OpenAIRE

    Cuadrado Ciuraneta, Sergi; Durà Guimerà, Antoni; Estalella Boadella, Helena

    2006-01-01

    En el presente artículo se presentan parte de los resultados de una investigación que se ha centrado en las transformaciones experimentadas desde la segunda mitad del siglo XX por los asentamientos en las áreas litorales de Cataluña y, más concretamente, en la llanura del Alt Empordà (Girona) como un ejemplo de las dinámicas de urbanización en las áreas litorales mediterráneas. Este es un territorio considerado emblemático porque mantenía un cierto equilibrio entre urbanización...

  7. TypeScript revealed

    CERN Document Server

    Maharry, Dan

    2013-01-01

    TypeScript Revealed is a quick 100-page guide to Anders Hejlsberg's new take on JavaScript. With this brief, fast-paced introduction to TypeScript, .NET, Web and Windows 8 application developers who are already familiar with JavaScript will easily get up to speed with TypeScript and decide whether or not to start incorporating it into their own development. TypeScript is 'JavaScript for Application-scale development'; a superset of JavaScript that brings to it an additional object-oriented-like syntax familiar to .NET programmers that compiles down into simple, clean JavaScript that any browse

  8. The prevalence and relative risk of drink and drug driving in the Netherlands: a case-control study in the Tilburg police district : research in the framework of the European research programme IMMORTAL (Impaired Motorists, Methods of Roadside Testing and Assessment for Licensing).

    NARCIS (Netherlands)

    Mathijssen, M.P.M. & Houwing, S.

    2005-01-01

    Drink and drug driving can have an impact on the driving performance and accident risk. This epidemiological study, which forms part of the European project IMMORTAL, investigates the prevalence of eight defined drug groups, including alcohol, among drivers in the Tilburg police district. To examine

  9. Telomere elongation chooses TERRA ALTernatives

    OpenAIRE

    Arora, Rajika; Azzalin, Claus M.

    2015-01-01

    Alternative Lengthening of Telomeres (ALT) mechanisms allow telomerase-negative immortal cells to buffer replicative telomere shortening. ALT is naturally active in a number of human cancers and might be selected upon telomerase inactivation. ALT is thought to operate through homologous recombination (HR) occurring between telomeric repeats from independent chromosome ends. Indeed, suppression of a number of HR factors impairs ALT cell proliferation. Yet, how HR is initiated at ALT telomeres ...

  10. Multifunctional electroactive electrospun nanofiber structures from water solution blends of PVA/ODA-MMT and poly(maleic acid-alt-acrylic acid): effects of Ag, organoclay, structural rearrangement and NaOH doping factors

    Science.gov (United States)

    Şimşek, Murat; Rzayev, Zakir M. O.; Bunyatova, Ulviya

    2016-06-01

    Novel multifunctional colloidal polymer nanofiber electrolytes were fabricated by green reactive electrospinning nanotechnology from various water solution/dispersed blends of poly (vinyl alcohol-co-vinyl acetate) (PVA)/octadecyl amine-montmorillonite (ODA-MMT) as matrix polymer nanocomposite and poly(maleic acid-alt-acrylic acid) (poly(MAc-alt-AA) and/or its Ag-carrying complex as partner copolymers. Polymer nanofiber electrolytes were characterized using FTIR, XRD, thermal (DSC, TGA-DTG), SEM, and electrical analysis methods. Effects of partner copolymers, organoclay, in situ generated silver nanoparticles (AgNPs), and annealing procedure on physical and chemical properties of polymer composite nanofibers were investigated. The electrical properties (resistance, conductivity, activation energy) of nanofibers with/without NaOH doping agent were also evaluated. This work presented a structural rearrangement of nanofiber mats by annealing via decarboxylation of anhydride units with the formation of new conjugated double bond sites onto partner copolymer main chains. It was also found that the semiconductor behaviors of nanofiber structures were essentially improved with increasing temperature and fraction of partner copolymers as well as presence of organoclay and AgNPs in nanofiber composite.

  11. Multifunctional electroactive electrospun nanofiber structures from water solution blends of PVA/ODA–MMT and poly(maleic acid-alt-acrylic acid): effects of Ag, organoclay, structural rearrangement and NaOH doping factors

    Science.gov (United States)

    Şimşek, Murat; Rzayev, Zakir M. O.; Bunyatova, Ulviya

    2016-06-01

    Novel multifunctional colloidal polymer nanofiber electrolytes were fabricated by green reactive electrospinning nanotechnology from various water solution/dispersed blends of poly (vinyl alcohol-co-vinyl acetate) (PVA)/octadecyl amine-montmorillonite (ODA–MMT) as matrix polymer nanocomposite and poly(maleic acid-alt-acrylic acid) (poly(MAc-alt-AA) and/or its Ag-carrying complex as partner copolymers. Polymer nanofiber electrolytes were characterized using FTIR, XRD, thermal (DSC, TGA–DTG), SEM, and electrical analysis methods. Effects of partner copolymers, organoclay, in situ generated silver nanoparticles (AgNPs), and annealing procedure on physical and chemical properties of polymer composite nanofibers were investigated. The electrical properties (resistance, conductivity, activation energy) of nanofibers with/without NaOH doping agent were also evaluated. This work presented a structural rearrangement of nanofiber mats by annealing via decarboxylation of anhydride units with the formation of new conjugated double bond sites onto partner copolymer main chains. It was also found that the semiconductor behaviors of nanofiber structures were essentially improved with increasing temperature and fraction of partner copolymers as well as presence of organoclay and AgNPs in nanofiber composite.

  12. 献血者丙氨酸氨基转移酶不同方法测定研究%DETERMINATION OF ALT BY DIFFERENT METODS IN BLOOD DONORS

    Institute of Scientific and Technical Information of China (English)

    潘彤; 张孝山; 李研; 李忠平

    2004-01-01

    [目的]使用速率法和微板法对献血者样品进行丙氨酸氨基转移酶(ALT)检测比较.[方法]对献血者样品进行两种方法ALT检测,分别比较初、复检结果的阳性率.[结果]速率法检测初筛样品9589份,阳性样品377份,阳性率3.93%;微板法检测初筛样品37633份,检出阳性标本1861份,阳性率4.95%,两种方法相比有显著差别(P<0.005);速率法检测复检样品4455份,阳性样品40份,阳性率0.90%;微板法检测初筛样品34894份,检出阳性标本702份,阳性率2.01%,两种方法x2检验有极显著差异(P<0.001).[结论]微板法测定ALT的影响因素很多,存在较多的假阳性和假阴性,建议使用自动生化分析仪测定ALT.

  13. Revealing the programming process

    DEFF Research Database (Denmark)

    Bennedsen, Jens; Caspersen, Michael Edelgaard

    2005-01-01

    One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because the textb......One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because...... the textbook medium is static and therefore ill-suited to expose the process of programming. We have found that process recordings in the form of captured narrated programming sessions are a simple, cheap, and efficient way of providing the revelation.We identify seven different elements of the programming...... process for which process recordings are a valuable communication media in order to enhance the learning process. Student feedback indicates both high learning outcome and superior learning potential compared to traditional classroom teaching....

  14. 中国四家参考实验室间ALT和AST的测定结果比对分析%Comparison of measurements for ALT and AST among four domestic reference laboratories

    Institute of Scientific and Technical Information of China (English)

    夏昌宇; 张雪莲; 徐国宾; 刘岩; 郭红雁; 孙桂珍; 黄宪章; 庄俊华; 于琴; 刘牧龙; 王兰珍

    2009-01-01

    目的 调查我国4家参考实验室应用国际临床化学联合会(IFCC)推荐加和不加磷酸吡哆醛参考方法测定ALT和AST的室内和室间变异,为设定合适的室内和室间变异的范围提供依据.方法 建立加和不加磷酸毗哆醛的IFCC方法,用均一性良好的5个浓度冰冻混合人血清作为比对材料,观察各实验室测量比对样本的室内和室间变异,并与2006年和2007年参考实验室外部质量评价计划(RALE)的结果做比较.同时分析加与不加磷酸吡哆醛时AST、ALT测定值及AST/ALT比值的差异.结果 本次比对的室间变异大于室内变异,仅个别实验室在个别结果出现室内变异大于室间变异的情况.室内变异不大于RELA比对室内变异的变化,室间变异亦明显小于后者.加磷酸吡哆醛法的ALT和AST测量值均比未加法高,两种方法得到的AST/ALT比值具有显著性差异.结论 建议酶学参考实验室ALT、AST测定室内变异分别小于2.72%、2.58%;使用冰冻血清作比对材料时,二者的室间变异小于3.5%;冰冻干燥品作比对材料时,二者的室间变异小于4.5%,应观察不同个体样本加和不加磷酸吡哆醛转氨酶测定值及其比值的变化在疾病诊断与预后评估中的临床意义.%Objective To investigate the intralaboratury and interlabomtory variations of measurements for ALT and AST among four domestic reference laboratories. Methods The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference procedures and IFCC procedures without pyridoxal 5-phosphate (PLP) were performed in the reference laboratories. Intralaboratory and interlaboratory CVs were compared with those in 2006 and 2007 IFCC External Quality Assessment Scheme for Reference Laboratories (RELA). Meanwhile, deviations of results for ALT, AST and AST/ALT between two methods were calculated. Results Interlaboratory CVs were generally higher than intralaboratory CVs. Interlaboratory CVs

  15. Revealing Cosmic Rotation

    CERN Document Server

    Yadav, Amit P S; Keating, Brian G

    2012-01-01

    Cosmological Birefringence (CB), a rotation of the polarization plane of radiation coming to us from distant astrophysical sources, may reveal parity violation in either the electromagnetic or gravitational sectors of the fundamental interactions in nature. Until only recently this phenomenon could be probed with only radio observations or observations at UV wavelengths. Recently, there is a substantial effort to constrain such non-standard models using observations of the rotation of the polarization plane of cosmic microwave background (CMB) radiation. This can be done via measurements of the $B$-modes of the CMB or by measuring its TB and EB correlations which vanish in the standard model. In this paper we show that $EB$ correlations-based estimator is the best for upcoming polarization experiments. The $EB$ based estimator surpasses other estimators because it has the smallest noise and of all the estimators is least affected by systematics. Current polarimeters are optimized for the detection of $B$-mode...

  16. Chemistry of plutonium revealed

    International Nuclear Information System (INIS)

    In 1941 one goal of the Manhattan Project was to unravel the chemistry of the synthetic element plutonium as rapidly as possible. In this paper the work carried out at Berkeley from the spring of 1942 to the summer of 1945 is described briefly. The aqueous chemistry of plutonium is quite remarkable. Important insights were obtained from tracer experiments, but the full complexity was not revealed until macroscopic amounts (milligrams) became available. Because processes for separation from fission products were based on aqueous solutions, such solution chemistry was emphasized, particularly precipitation and oxidation-reduction behavior. The latter turned out to be unusually intricate when it was discovered that two more oxidation states existed in aqueous solution than had previously been suspected. Further, an equilibrium was rapidly established among the four aqueous oxidation states, while at the same time any three were not in equilibrium. These and other observations made while doing a crash study of a previously unknown element are reported

  17. Estudio histopatológico de hígado y riñón de caninos y su relación con las concentraciones de urea, creatinina, proteínas, enzimas (ALT y SAP en sangre premortem y en humor acuoso a las 0 y 24 horas postmortem Histopathological study of canine liver and kidney and their relationship with blood and postmortem aqueous humour samples concentrations of urea, creatinine, proteins and enzymes activities (ALT and SAP

    Directory of Open Access Journals (Sweden)

    C. GALLARDO

    2003-01-01

    Full Text Available Se necropsiaron 31 caninos, sin historia clínica de patologías hepáticas o renales. Previo a la eutanasia, realizada con solución sobresaturada de tiopental sódico, se obtuvo una muestra de plasma; una vez efectuada la eutanasia, se obtuvo una muestra de humor acuoso desde el ojo derecho y otra 24 h después del ojo izquierdo. En cada muestra se determaron las concentraciones de urea, creatinina, proteínas, ALT y SAP. Se caracterizaron las lesiones histológicas de hígado y de riñón de caninos a fin de relacionarlas con las concentraciones de urea, creatinina, proteínas, ALT y SAP en sangre premortem y en humor acuoso a las 0 y 24 h postmortem. A cada perro se le practicó una necropsia, obteniéndose muestras de hígado y riñón en formalina al 10%. Para la caracterización histológica de las lesiones se utilizó la siguiente escala: ausente (0, leve (I, moderado (II, marcado (III, y severo (IV. A cada órgano se le asignó un grado de alteración histológica utilizando una escala similar (I a IV; este grado de alteración fue comparado con las concentraciones de los metabolitos estudiados en sangre y humor acuoso a las 0 y 24 h postmortem. El 100% de los perros manifestó algún grado de alteración renal y hepática (G.A.R. y G.A.H.. Los trastornos de tipo inflamatorio necrótico a nivel renal fueron observados en el 100% de los perros, destacándose la glomerulonefritis (100% y la nefritis intersticial (87.09%. A nivel hepático los trastornos de tipo circulatorio fueron los más frecuentemente observados (100%, siendo la congestión difusa la lesión más encontrada (63.33%. Las concentraciones de los metabolitos estudiados fueron mayores en sangre premortem que en humor acuoso a las 0 y 24 h postmortem (pThe goal of this study was to characterize histopathological lesions of the liver and kidney of canines, and their relationship with blood and postmortem samples of aqueous humor concentrations of urea, creatinine, proteins

  18. Genetic dissection of an elite rice hybrid revealed that heterozygotes are not always advantageous for performance.

    OpenAIRE

    Hua, J P; Xing, Y Z; Xu, C. G.; Sun, X L; Yu, S B; Zhang, Qifa

    2002-01-01

    We introduced an experimental design that produced an "immortalized F(2)" population allowing for complete dissection of genetic components underlying quantitative traits. Data for yield and three component traits of the immortalized F(2) were collected from replicated field trials over 2 years. Using 231 marker loci, we resolved the genetic effects into individual components and assessed relative performance of all the genotypes at both single- and two-locus levels. Single-locus analysis det...

  19. Altérité et inclusion. Du corps propre au corps social en classe de langue : emprunts à la danse contemporaine

    Directory of Open Access Journals (Sweden)

    Marie-Paule Muller-Jaecki

    2013-11-01

    The foreign language class implies a transformation of the learner’s own body in order to access a new social body. Does it thereby handicap pupils, generating suffering? Is it possible to avoid this? The following reflection starts from the observation of experiences in contemporary dance, related to the creation of performances including disabled dancers. The analysis of the pedagogy reveals constants which contribute to the inclusion of every dancer. It can inspire teachers in order to design a foreign language learning approach in which each pupil feels competent.

  20. Comparability study of ALT detection by three biochemistry analyzer systems and the influence to ALT activity with the existence of coenzyme pyridoxal-5-phosphate.%辅酶磷酸吡哆醛的存在对三种生化检测系统测定丙氨酸氨基转移酶活性的影响及其可比性研究

    Institute of Scientific and Technical Information of China (English)

    张建忠; 沈春燕

    2011-01-01

    To study the difference and comparability of alanine aminotransferase (ALT) results detected by three biochemistry analyzer systems. Methods The ALT activities of 164 cases of patients and 152 cases of healthy adults were detected by DADE Dimension RXL system, Johnson Vitros-350 system that containing pyridoxal-5-phosphate in their reagents and HITACHI7170 system that not containing pyridoxal-5-phosphate in its reagents,respectively. According to the document EP9-A described by the NCCLS, two group parallel contrast tests had being established: In the first group, ALT detected by HITACHI7170 system was selected as the standard method and DADE Dimension RXL system as the empirical method. In the other group, ALT detected by DADE Dimension RXL system was selected as the standard method and Johnson Vitros-350 system as the empirical method. Results The assay resuits of ALT activity detected by DADE Dimension RXL and Johnson Vitros-350 systems were higher(20.2%~56.5%)than that detected by HITACHI7170 system and there was no significant difference between DADE Dimension RXL system and Johnson Vitros-350 system. The parallel contrast tests also showed that there was an obvious systematic error between HITACHI7170 system and DADE Dimension RXL system, but there was a good correlation between DADE Dimension RXL system and Vitros-350 system. Conclusion Because of the difference of methodology the results of ALT activity detected by DADE Dimension RXL and Johnson Vitros-350 biochemistry analyzer systems couldn't obtain consistency with those by HITACHI7170 system, but there was a higher consistency between DADE Dimension RXL system and Vitros-350 system.%目的 探讨不同生化检测系统间测定丙氨酸氨基转移酶(ALT)活性结果的差异及其可比性.方法 使用ALT试剂中含有磷酸吡哆醛的DADE Dimension RXL检测系统、强生Vitros-350检测系统以及ALT试剂中未含有磷酸吡哆醛HITACHI7170检测系统同时测试164例患者和152例

  1. Altın ve Amalgamların Muhtelif Değişkenler Karşısında Gösterdikleri Galvanismus, in Vitro Bir Çalışma

    OpenAIRE

    OKTAY, Cengiz

    2013-01-01

    SONUÇ ve ÖZET :Bu araştırmada farklı elektrik potansiyelindeki 22 ayar altın ve ince grenli veya folie amalgamlar arasında değişlik PH'larda, değişik amalgam civa oranlarında, değişik karıştırma zamanlarında geçen süre ile teşekkül eden galvanik akım potansiyel farkları in vitro olarak tetkik edilmiştir. Bu tetkiklerde gözlenen tandanslar :Tandanslar % 95 güvenirlik ile verilmiştir. Bu tandanslar ince grenli solila amalgamı için :1 — Geçen zaman galvanik akımı negatif yönde etkilemektedir.2...

  2. Effect of Total Alkaloid of Herba Desmodii Pulchelli on Serum HA and ALT of Rats with Hepatic Fibrosis%排钱草总生物碱对肝纤维化大鼠血清HA、ALT的影响

    Institute of Scientific and Technical Information of China (English)

    杨增艳; 黄琳芸; 钟鸣; 余胜民

    2002-01-01

    @@ 排钱草[Desmodium pulchellum(L.)Benth]为民间常用草药,一般用来治疗急、慢性肝炎、肝硬化等疾病.钟氏等[1]曾报道排钱草的水、醇提物均能显著降低肝纤维化大鼠肝脏中羟脯氨酸(Hyp)含量,减少大鼠肝细胞坏死和减轻胶原纤维增生.为进一步探讨排钱草抗肝纤维化作用的有效成分及其作用机理,我们就排钱草总生物碱对肝纤维化大鼠血清中的透明质酸(HA)、谷丙转氨酶(ALT)指标进行研究.

  3. Sağlıklı ve Subklinik Mastitisli İneklerde Kan Serumu ALP, ALT ve Glukoz Düzeyleri Üzerine Çalışma

    OpenAIRE

    Yüksel, Murat; KANDEMİR, Fatih Mehmet; DEVECİ, Hüseyin; ÖZDEMİR, Necmi

    2010-01-01

    Bu çalıĢmada, subklinik mastitisli ineklerin serum alkalen fosfataz (ALP), alanin aminotransferaz (ALT) ve glukoz düzeyleri ölçülerek, subklinik mastitis ile bu parametrelerin aktivitesi arasındaki iliĢki araĢtırıldı. ÇalıĢmada çeĢitli yaĢ ve ırklardan 10’u sağlıklı (kontrol), 10’u da subklinik mastitisli toplam 20 inek materyal olarak kullanıldı. Hayvanlarda mastitis teĢhisi California Mastitis Test (CMT) ve mikrobiyolojik muayene ile ya...

  4. Mason’un Bilişim Etiği Boyutları Altında Vikipedi’nin İncelenmesi

    Directory of Open Access Journals (Sweden)

    Şenay Ozan

    2014-03-01

    Full Text Available The aim of this study was to investigate Wikipedia under the light of the dimensions of informatic ethics according to Mason (1986. Data set of this study was designed as qualitative research design and was collected by small focus group interview. The participants of the study were eight teacher candidates in the department of computer and instructional technology education in University of Anadolu. Interviews were carried out as four small focus group interviews including one male and one female from each grade level. The obtained data was analyzed with content analysis. Concordantly the data was organized and Wikipedia was investigated under the light of dimensions of information ethics. Results were discussed under two headings. The first as being, participants awareness regarding information ethics; and the second as being participants point of views on Wikipedia regarding the aspects of privacy, accuracy, property and accessibility. Results on participants awareness regarding information ethics revealed that they had not a structured knowledge on information ethics, but were familiar with the issue as can be understood by the informal examples they used. Results related with accessibility indicated that Vikipedi has high accessibility. Findings related to accuracy and intellectual property reveal that ethical problems are rather user based, note the environment. There came a theme which can be titled under ethical considerations regarding Wikipedia use which presented participants hesitations on entering issues without any control. Under the light of the findings of this study, we came to an understanding of a necessity for more information web 2.0 technologies. This may require a web 2.0 literacy training for teacher candidates

  5. Puerto Rico Revealed Preference data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Revealed preference models provide insights into recreational angler behavior and the economic value of recreational fishing trips. Revealed preference data is...

  6. Angiogenesis interactome and time course microarray data reveal the distinct activation patterns in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Liang-Hui Chu

    Full Text Available Angiogenesis involves stimulation of endothelial cells (EC by various cytokines and growth factors, but the signaling mechanisms are not completely understood. Combining dynamic gene expression time-course data for stimulated EC with protein-protein interactions associated with angiogenesis (the "angiome" could reveal how different stimuli result in different patterns of network activation and could implicate signaling intermediates as points for control or intervention. We constructed the protein-protein interaction networks of positive and negative regulation of angiogenesis comprising 367 and 245 proteins, respectively. We used five published gene expression datasets derived from in vitro assays using different types of blood endothelial cells stimulated by VEGFA (vascular endothelial growth factor A. We used the Short Time-series Expression Miner (STEM to identify significant temporal gene expression profiles. The statistically significant patterns between 2D fibronectin and 3D type I collagen substrates for telomerase-immortalized EC (TIME show that different substrates could influence the temporal gene activation patterns in the same cell line. We investigated the different activation patterns among 18 transmembrane tyrosine kinase receptors, and experimentally measured the protein level of the tyrosine-kinase receptors VEGFR1, VEGFR2 and VEGFR3 in human umbilical vein EC (HUVEC and human microvascular EC (MEC. The results show that VEGFR1-VEGFR2 levels are more closely coupled than VEGFR1-VEGFR3 or VEGFR2-VEGFR3 in HUVEC and MEC. This computational methodology can be extended to investigate other molecules or biological processes such as cell cycle.

  7. Senescence mechanism and immortalization of human bone marrow mesenchymal stem cells%人骨髓间充质干细胞的衰老机制及其"永生化"技术

    Institute of Scientific and Technical Information of China (English)

    黄炜; 吕安林; 刘博武; 候婧; 李垚; 燕学波

    2011-01-01

    背景:人类骨髓间充质干细胞由于其自身特性,被认为是最有潜力修复坏死心肌的干细胞,并已成为心肌组织工程研究的热点.目的:回顾分析人类骨髓间充质干细胞的衰老机制及根据这些机制建立的人类骨髓间充质干细胞永生化方法.方法:由第一作者检索1990/2010 PubMed数据库、万方数据库及Springer、Science Direct数据库有关骨髓间充质干细胞衰老机制及其永生化方法等方面的文献.结果与结论:骨髓间充质干细胞在体外培养传代过程中存在着细胞老化、干细胞样特征丢失的现象,阻碍了其在临床的广泛应用.通过对p53-p21及p16-pRb等信号通路细胞衰老分子机制的深入了解,研究者们试图建立永生化的骨髓间充质干细胞,包括将HPV16 E6E7蛋白的基因转入人骨髓间充质干细胞建立的KP细胞系,或将端粒末端转移酶反转录酶的片段 phTERT -IRES2-EGFP转染入KP细胞,建立3A6细胞系等方法,均在一定程度上延长了骨髓间充质干细胞寿命.但由于利用病毒载体进行基因转染方法带来的基因重组和插入突变等风险及细胞的固有抗病毒反应导致转染成功率较低,因而大量研究集中在了寻找非基因干涉方法上,建立标准化的永生化骨髓间充质干细胞的方法有待进一步研究.%BACKGROUND: Human bone marrow mesenchymal stem cells (hBMSCs) due to its property are considered one of the most promising stem cell for regeneration of the injured myocardiocytes, and have become the hot point for the study of myocardial tissue engineering.OBJECTIVE: To retrospectively analyze senescence mechanism of hBMSCs and to establish immortalized method of hBMSCs according to these mechanisms.METHODS: The first author retrieved PubMed Database, Wanfang Database, Springer and Science Direct Database for articles on senescence mechanism of hBMSCs and the immortalized method published from 1990 to 2010.RESULTS AND CONCLUSION

  8. Revealing the Beast Within

    Science.gov (United States)

    2003-07-01

    Deeply Embedded Massive Stellar Clusters Discovered in Milky Way Powerhouse Summary Peering into a giant molecular cloud in the Milky Way galaxy - known as W49 - astronomers from the European Southern Observatory (ESO) have discovered a whole new population of very massive newborn stars . This research is being presented today at the International Astronomical Union's 25th General Assembly held in Sydney, Australia, by ESO-scientist João Alves. With the help of infrared images obtained during a period of excellent observing conditions with the ESO 3.5-m New Technology Telescope (NTT) at the La Silla Observatory (Chile), the astronomers looked deep into this molecular cloud and discovered four massive stellar clusters, with hot and energetic stars as massive as 120 solar masses. The exceedingly strong radiation from the stars in the largest of these clusters is "powering" a 20 light-year diameter region of mostly ionized hydrogen gas (a "giant HII region"). W49 is one of the most energetic regions of star formation in the Milky Way. With the present discovery, the true sources of the enormous energy have now been revealed for the first time, finally bringing to an end some decades of astronomical speculations and hypotheses. PR Photo 21a/03 : Colour Composite of W49A (NTT+SOFI). PR Photo 21b/03 : Radio and Near-Infrared Composite of W49A Giant molecular clouds Stars form predominantly inside Giant Molecular Clouds which populate our Galaxy, the Milky Way. One of the most prominent of these is W49 , which has a mass of a million solar masses. It is located some 37,000 light-years away and is the most luminous star-forming region known in our home galaxy: its luminosity is several million times the luminosity of our Sun. A smaller region within this cloud is denoted W49A - this is one of the strongest radio-emitting areas known in the Galaxy . Massive stars are excessive in all ways. Compared to their smaller and ligther brethren, they form at an Olympic speed and

  9. Evento com aparente risco de morte: uma revisão Evento con aparente riesgo de muerte (alte: una revisión Apparent life-threatening event: a review

    Directory of Open Access Journals (Sweden)

    Mariana Tresoldi das N. Romaneli

    2012-12-01

    Full Text Available OBJETIVO: Realizar uma revisão crítica reunindo informações disponíveis a respeito dos eventos com aparente risco de morte. FONTES DE DADOS: Revisão bibliográfica dos artigos (em português, inglês e espanhol obtidos dos bancos de dados eletrônicos Medline, Lilacs e SciELO, utilizando as palavras-chave: eventos com aparente risco de morte, evento com aparente risco de vida infantil, lactente, apneia, monitorização e cianose. SÍNTESE DOS DADOS: Os eventos com aparente risco de mortesão súbitos e caracterizados por uma combinação de apneia, alteração na coloração da pele e tônus muscular, com inúmeras causas subjacentes. Sua incidência verdadeira é desconhecida e a faixa etária mais acometida é de 11 a 12 semanas. Não há correlação entre o evento com aparente risco de morte e a síndrome da morte súbita do lactente, embora já tenham sido consideradas manifestações da mesma doença. Muitas vezes, o lactente tem aparência saudável ao ser avaliado pelo pediatra após apresentar eventos com aparente risco de morte, porém, isso não afasta a possibilidade de existir uma doença grave associada ao evento, que deve ser investigada e tratada. Quando não são encontradas as causas, o evento é idiopático, geralmente com boa evolução. CONCLUSÕES: É necessário investigar os lactentes levados ao pronto-socorro após apresentarem eventos com aparente risco de morte, devido ao risco de sequelas e mortalidade. Não há uma padronização das condutas a serem realizadas diante de um lactente com aparência saudável que tenha evento com aparente risco de morte, mas recomenda-se que o paciente seja internado e a causa do evento, investigada. A observação e o monitoramento em ambiente hospitalar devem ocorrer no mínimo 24 horas após o evento.OBJETIVO: Realizar una revisión crítica, reuniendo las informaciones disponibles respecto a los Eventos con Aparente Riesgo de Muerte (ALTE - Apparent life-threatening event

  10. The Clinical Research into Acute Pelvic Inflammatory Disease Treated with Supplemented Immortal Formula Life-Giving Beverage%仙方活命饮加味治疗急性盆腔炎临床研究

    Institute of Scientific and Technical Information of China (English)

    刘志红; 邹艳芬

    2016-01-01

    目的:观察仙方活命饮加味治疗急性盆腔炎的临床疗效.方法:选取2011年12月-2013年12月本院治疗的急性盆腔炎患者116例为研究对象,随机分成对照组和观察组,每组58例.对照组给予头孢曲松2.0g加入0.9%氯化钠注射液100 mL静脉滴注,盐酸多西环素100 mg加入0.9%氯化钠注射液100 mL静脉滴注,观察组在对照组治疗的基础上加用仙方活命饮加味治疗.结果:对照组有效率82.76%,观察组有效率93.1%,观察组优于对照组(P<0.05);观察组治疗后高切血黏度、低切血黏度、红细胞压积、血小板黏附率均优于对照组(P<0.05);观察组治疗后白细胞、C反应蛋白、炎性包块、盆腔积液水平均优于对照组(P<0.05).结论:仙方活命饮加味治疗急性盆腔炎疗效显著.%Objective:To observe the clinical curative effect of Supplemented Immortal Formula Life-Giving Beverage on acute pelvic inflammatory disease.Methods:One hundred and sixteen patients with acute pelvic inflammatory disease who were treated in our hospital between December of 2011 and December of 2013 were chosen as the research objects,and randomly divided into the control group and the observation group,with 58 cases in each group.The ones in the control group were given 2.0 g of ceftriaxone mixed with 100 mL of sodium chloride injection with 0.9% concentration for intravenous drip,100 mg of hydrochloride doxycycline mixed with 100ml of sodium chloride injection with 0.9% concentration for intravenous drip,while the ones in the observation group were added Supplemented Immortal Formula Life-Giving Beverage based on the treatment of the control group.Results:The effective rate of the control group was 82.76%,while that of the observation group was 93.1%;And the observation group was better than the control group (P <0.05).After the treatment,high blood viscosity,low shear blood viscosity,hematocrit and platelet adhesion rate of the observation group

  11. 一种永生化的大鼠颈动脉血管球细胞系的生化特性%The neurochemical properties of an immortalized glomus cell line from the carotid body of rat

    Institute of Scientific and Technical Information of China (English)

    周光斗

    2006-01-01

    目的 神经干细胞在帕金森病的治疗中有十分巨大的潜在价值,然而,神经干细胞含有多种神经细胞成分,目前选择性分离纯化其中的多巴胺能神经元尚不完全成熟.在这里我们报告一种来自颈动脉体的克隆细胞系.方法 我们用逆转录病毒转导SV40 T抗原和Cre/lox P到大鼠颈动脉血管球细胞使其永生化,然后这些原癌基因被腺病毒转导的Cre重组酶切除.结果 克隆的血管球细胞表达高水平的酪氨酸羟化酶免疫反应性物质并且选择性地释放多巴胺.这些克隆细胞几乎不表达多巴胺转运体(DAT)而且抵抗多巴胺和MPTP介导的神经毒性.结论 克隆的血管球细胞可能为帕金森病的治疗提供一种新的方法.%Objective Embryonic stem cells (ES) are potentially useful for treatment of Parkinson's disease. However, ES cells contain a mixed population of neurons, and selective enrichment of dopaminergic components remains difficult. Here, we report that a dopaminergic clonal cell line developed from carotid body. Methods Glomus cells of the rat carotid body were conditionally immortalized by retroviral transfer of the SV40 T antigen and Cre/lox P elements. The oncogene was subsequently removed adenoviral delivery of the Cre recombinase. Results Cloned glomus cells expressed high levels of tyrosine hydroxylase immunoreactivity and selectively released dopamine in culture. Remarkably, they expressed little dopamine transporter DAT, and were resistant to dopamine- and MPTP-mediated neurotoxicity. Conclusion Immortalized glomus cell line might provide an alternative way to the treatment of Parkinson's disease.

  12. Epidermal growth factor suppresses insulin-like growth factor binding protein 3 levels in human papillomavirus type 16-immortalized cervical epithelial cells and thereby potentiates the effects of insulin-like growth factor 1.

    Science.gov (United States)

    Hembree, J R; Agarwal, C; Eckert, R L

    1994-06-15

    Human ectocervical epithelial cells are a primary target for infection by oncogenic papillomaviruses, which are strongly implicated as causative agents in the genesis of cervical cancer. Growth factors have been implicated as agents that stimulate proliferation and enhance the possibility of malignant transformation. In the present study we utilize several human papillomavirus (HPV) type 16-immortalized ectocervical epithelial cell lines to investigate the effects of epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) on cell proliferation and the production of IGF binding proteins (IGFBPs). ECE16-1 cells, an HPV16-immortalized/nontumorigenic cell line, maintained in defined medium, produce and release high levels of IGFBP-3 (38/42 kDa) as well as smaller amounts of a 24-kDa IGFBP. Supplementation of defined medium with EGF causes a dose-dependent increase in cell growth and a concomitant decrease in the levels of IGFBP-3 released into the culture medium. EGF suppression of IGFBP-3 is maintained even when EGF-stimulated cell growth is suppressed 67% due to the simultaneous presence of 3 ng/ml of TGF beta 1, indicating that EGF suppression of IGFBP-3 levels is independent of EGF effects on cell growth. EGF suppression of IGFBP-3 production is correlated with a reduction in IGFBP-3 mRNA level. In the presence of EGF, the growth response of the cells to ng amounts of IGF-I is significantly enhanced. Moreover, the simultaneous presence of both EGF and IGF-I reduces the level of IGFBP-3 more efficiently than EGF alone. We also observe that the IGFBP-3 level is decreased and the 24-kDa IGFBP level is increased in HPV16-positive tumorigenic versus nontumorigenic cell lines. This is the first report of EGF acting as a positive regulator of IGF-I action via the IGFBPs. On the basis of these findings, we propose that EGF stimulates ECE16-1 cell growth via a dual-action mechanism by (a) stimulating growth directly via the EGF mitogenic pathway and (b

  13. Comparative study of four immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, and optimization of culture conditions, for an in vitro blood–brain barrier model for drug permeability studies

    OpenAIRE

    Eigenmann, Daniela E; Xue, Gongda; Kwang S Kim; Moses, Ashlee V.; Hamburger, Matthias; Oufir, Mouhssin

    2013-01-01

    Background Reliable human in vitro blood–brain barrier (BBB) models suitable for high-throughput screening are urgently needed in early drug discovery and development for assessing the ability of promising bioactive compounds to overcome the BBB. To establish an improved human in vitro BBB model, we compared four currently available and well characterized immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, with respect to barrier tightness and paracellu...

  14. Al2024-T3合金热变形加工工艺的流变应力预测%Flow stress prediction for hot deformation processing of 2024Al-T3 alloy

    Institute of Scientific and Technical Information of China (English)

    D. TRIMBLE; G. E. O’DONNELL

    2016-01-01

    Isothermal compression tests were conducted to predict the hot deformational flow stress behaviour of 2024Al-T3 alloy with respect to a wide range of strain rates (0.001−100 s−1), strains (0.1−0.5) and temperatures (573−773 K). The prediction capabilities of various constitutive models for 2024Al alloys and a recently developed constitutive model were evaluated using statistical parameters such as the average absolute relative error (AARE) and the correlation coefficient (R). Models recorded the lowest AARE (4.6%) and the highest correlation coefficient (R=0.99) were developed compared with the other models. Hence, this model can track the deformational behaviour of 2027Al-T3 alloy more accurately compared with other models throughout the entire processing domain investigated.%为了预测Al2024-T3合金热变形加工工艺的流变应力行为,在应变速率(0.001~100 s−1)、应变(0.1~0.5)和温度(573~773 K)条件下,进行了等温压缩试验。采用统计参数,如平均相对误差绝对值(AARE)和相关系数(R)评估了Al2024合金不同的本构模型和最新构建的本构模型的预测能力。与其他的模型相比,最新构建的模型能得到最低的AARE(4.6%)和最高的相关系数(0.99)。因此,与其他模型相比,该模型能更精确地描述Al2027-T3合金的变形行为。

  15. Regard Death as Life-Concept of After Life in Stories of Immortals%视死如生--略论《搜神记》的死后世界观

    Institute of Scientific and Technical Information of China (English)

    李文智

    2016-01-01

    The Concept of afterlife in Stories of Immortals is not only reflects the wei-jin period religious complex situation,but also clearly reflects the Chinese original concept of afterlife and it`s evolution ,with human nature growing,the afterlife straight like the human version .Although the concept of afterlife has different expression,it is still the different expression of Chinese original concept of afterlife in the new era ,and shows no obvious foreign religious color.%《搜神记》的死后世界观不仅反映了魏晋时期宗教信仰的复杂状况,而且也明显地反映出中国原有死后世界观的嬗变情况,人性化不断增强,直似人间的翻版。《搜神记》对于死后世界观有不同表述,但所表现的仍然是中国本土原有的死后世界观在新的时代背景下承前启后的新阐释,并没有表现出明显的外来宗教色彩。

  16. 延边地区非酒精性脂肪肝患者血中ALT及adiponectin值的关系%STUDY ON THE RELATIONSHIP BETWEEN SERUM ADIPONECTIN LEVEL AND ALT AMONG MALES WITH NONALCOHOLIC FATTY LIVER DISEASE IN YANBIAN

    Institute of Scientific and Technical Information of China (English)

    韩学吉; 许顺姬

    2009-01-01

    [目的]分析非酒精性脂肪肝病(nonalcoholic fatty liver disease,NAFLD)患者血清ALT与adiponectin浓度及两者关系. [方法]选择B超诊断脂肪肝病男性患者238名,分为A群(ALT40 IU/L)118名,比较两群生化指标及adiponectin浓度,分析血清ALT及adiponectin浓度之间关系. [结果]两组间血清adiponectin有明显差异(3.89±1.77 vs 7.01±2.54μg/dl,P=0.001).另外,adiponectin和ALT呈负相关(r=-0.506,P=0.001). [结论]在单纯性脂肪肝发展成脂肪肝炎、肝纤维化的过程中adiponectin可能起着抗炎及护肝的作用,adiponectin也可以作为非酒精性脂肪肝炎发生的预测因子,对非酒精性脂肪肝炎的早期预防、早期诊断、早期治疗有重要的临床意义.

  17. Effects of Polydatin on ALT, AST, TNF-α, and COX-2 in Sepsis Model Mice%虎杖苷对小鼠脓毒症模型ALT、AST、TNF-α及COX-2的影响

    Institute of Scientific and Technical Information of China (English)

    李晓会; 吴孟娇; 张丽娜; 郑佳佳; 张力; 万敬员

    2013-01-01

    目的 研究虎杖苷对小鼠脓毒症致急性肝损伤的保护作用,并初步探讨其机制.方法 采用盲肠结扎穿孔(cecal ligation and puncture,CLP)小鼠脓毒症模型,并设假手术对照组.在CLP手术前1h,采用不同剂量虎杖苷(50、100、300 mg/kg)干预,随后每6h观察小鼠一般情况,24 h后处死存活小鼠,收集血清和肝组织样本.分别采用比色法检测血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)活性;采用酶联免疫法检测血清肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α )含量;采用免疫印迹法检测肝组织环氧合酶-2 (cyclooxygenase-2,COX-2)表达;并取部分肝组织进行病理组织学分析.结果 CLP后24 h,小鼠死亡率高达50%,生化指标和肝脏病理显示病变明显,模型成功率达90%,相对于假手术组,血清ALT、AST活性、TNF-α 水平和肝组织中COX-2蛋白表达显著升高(P<0.01);虎杖苷呈剂量依赖地改善脓毒症诱导的死亡率,抑制ALT、AST活性和TNF-α升高(P<0.05),降低肝组织中COX-2表达,减轻肝脏病理损伤.结论 虎杖苷有效地保护脓毒症诱导的急性肝损伤,其作用机制可能通过抑制TNF-α生成和COX-2的表达.%Objective To investigate the protective effects of polydatin on sepsis-induced acute liver injury (ALI) in mice, and to preliminarily study its mechanisms. Methods The sepsis model was established using cecal ligation and puncture (CLP). A sham-operation control group was also set up. Polydatin (50, 100, and 300 mg/kg, respectively) was administrated to mice 1 h before CLP. The survival and liver injury were evaluated subsequently per 6 h after CLP. The survived mice were scarified 24 h later. The serum and the liver tissue sample were collected. The serum alanine aminotransferase (ALT) and aspar-tate aminotransferase (AST) were detected by colorimetric method. The content of tumor necrosis factor-alpha (TNF-α) was assayed by ELISA. The

  18. Lenna Kuurmaa üllatas / Ode Alt

    Index Scriptorium Estoniae

    Alt, Ode

    2008-01-01

    Rainer Sarneti noortefilm "Kuhu põgenevad hinged?", stsenaariumi aluseks on Aidi Valliku romaanid Annist, kaasstsenarist Peeter Sauter, osades Ragne Veensalu, Lenna Kuurmaa jt. Filmi tootja Exitfilm. Loo autor on Tartu Descartes'i Lütseumi 12. klassi õpilane

  19. Alt av kærleika

    DEFF Research Database (Denmark)

    Joensen, Dagny

    I begyndelse af 1960’erne blev der bygget en Nato-radarstation på Færøerne, og den var de første år bemandet med amerikanske eksperter. Flere færøske kvinder blev gift med disse amerikanere og fulgte med dem tilbage til USA. I denne bog interviewes en række af disse kvinder...

  20. PRMT1-mediated methylation of MICU1 determines the UCP2/3 dependency of mitochondrial Ca(2+) uptake in immortalized cells.

    Science.gov (United States)

    Madreiter-Sokolowski, Corina T; Klec, Christiane; Parichatikanond, Warisara; Stryeck, Sarah; Gottschalk, Benjamin; Pulido, Sergio; Rost, Rene; Eroglu, Emrah; Hofmann, Nicole A; Bondarenko, Alexander I; Madl, Tobias; Waldeck-Weiermair, Markus; Malli, Roland; Graier, Wolfgang F

    2016-09-19

    Recent studies revealed that mitochondrial Ca(2+) channels, which control energy flow, cell signalling and death, are macromolecular complexes that basically consist of the pore-forming mitochondrial Ca(2+) uniporter (MCU) protein, the essential MCU regulator (EMRE), and the mitochondrial Ca(2+) uptake 1 (MICU1). MICU1 is a regulatory subunit that shields mitochondria from Ca(2+) overload. Before the identification of these core elements, the novel uncoupling proteins 2 and 3 (UCP2/3) have been shown to be fundamental for mitochondrial Ca(2+) uptake. Here we clarify the molecular mechanism that determines the UCP2/3 dependency of mitochondrial Ca(2+) uptake. Our data demonstrate that mitochondrial Ca(2+) uptake is controlled by protein arginine methyl transferase 1 (PRMT1) that asymmetrically methylates MICU1, resulting in decreased Ca(2+) sensitivity. UCP2/3 normalize Ca(2+) sensitivity of methylated MICU1 and, thus, re-establish mitochondrial Ca(2+) uptake activity. These data provide novel insights in the complex regulation of the mitochondrial Ca(2+) uniporter by PRMT1 and UCP2/3.