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Sample records for human pol ii

  1. Syndromes associated with Homo sapiens pol II regulatory genes.

    Science.gov (United States)

    Bina, M; Demmon, S; Pares-Matos, E I

    2000-01-01

    The molecular basis of human characteristics is an intriguing but an unresolved problem. Human characteristics cover a broad spectrum, from the obvious to the abstract. Obvious characteristics may include morphological features such as height, shape, and facial form. Abstract characteristics may be hidden in processes that are controlled by hormones and the human brain. In this review we examine exaggerated characteristics presented as syndromes. Specifically, we focus on human genes that encode transcription factors to examine morphological, immunological, and hormonal anomalies that result from deletion, insertion, or mutation of genes that regulate transcription by RNA polymerase II (the Pol II genes). A close analysis of abnormal phenotypes can give clues into how sequence variations in regulatory genes and changes in transcriptional control may give rise to characteristics defined as complex traits.

  2. Enhancer SINEs Link Pol III to Pol II Transcription in Neurons

    Directory of Open Access Journals (Sweden)

    Cristina Policarpi

    2017-12-01

    Full Text Available Summary: Spatiotemporal regulation of gene expression depends on the cooperation of multiple mechanisms, including the functional interaction of promoters with distally located enhancers. Here, we show that, in cortical neurons, a subset of short interspersed nuclear elements (SINEs located in the proximity of activity-regulated genes bears features of enhancers. Enhancer SINEs (eSINEs recruit the Pol III cofactor complex TFIIIC in a stimulus-dependent manner and are transcribed by Pol III in response to neuronal depolarization. Characterization of an eSINE located in proximity to the Fos gene (FosRSINE1 indicated that the FosRSINE1-encoded transcript interacts with Pol II at the Fos promoter and mediates Fos relocation to Pol II factories, providing an unprecedented molecular link between Pol III and Pol II transcription. Strikingly, knockdown of the FosRSINE1 transcript induces defects of both cortical radial migration in vivo and activity-dependent dendritogenesis in vitro, demonstrating that FosRSINE1 acts as a strong enhancer of Fos expression in diverse physiological contexts. : Spatiotemporal regulation of gene expression requires the interaction between promoters and distally located enhancers. Policarpi et al. identify a subset of SINEs that functions as enhancers for activity-dependent neuronal genes. The enhancer SINE FosRSINE1 regulates Fos transcription and is necessary for both activity-dependent dendritogenesis and proper brain development. Keywords: neuroscience, epigenetics, transcription, enhancers, SINEs, neuronal activity, neuronal development

  3. Involvement of specialized DNA polymerases Pol II, Pol IV and DnaE2 in DNA replication in the absence of Pol I in Pseudomonas putida

    International Nuclear Information System (INIS)

    Sidorenko, Julia; Jatsenko, Tatjana; Saumaa, Signe; Teras, Riho; Tark-Dame, Mariliis; Horak, Rita; Kivisaar, Maia

    2011-01-01

    The majority of bacteria possess a different set of specialized DNA polymerases than those identified in the most common model organism Escherichia coli. Here, we have studied the ability of specialized DNA polymerases to substitute Pol I in DNA replication in Pseudomonas putida. Our results revealed that P. putida Pol I-deficient cells have severe growth defects in LB medium, which is accompanied by filamentous cell morphology. However, growth of Pol I-deficient bacteria on solid rich medium can be restored by reduction of reactive oxygen species in cells. Also, mutants with improved growth emerge rapidly. Similarly to the initial Pol I-deficient P. putida, its adapted derivatives express a moderate mutator phenotype, which indicates that DNA replication carried out in the absence of Pol I is erroneous both in the original Pol I-deficient bacteria and the adapted derivatives. Analysis of the spectra of spontaneous Rif r mutations in P. putida strains lacking different DNA polymerases revealed that the presence of specialized DNA polymerases Pol II and Pol IV influences the frequency of certain base substitutions in Pol I-proficient and Pol I-deficient backgrounds in opposite ways. Involvement of another specialized DNA polymerase DnaE2 in DNA replication in Pol I-deficient bacteria is stimulated by UV irradiation of bacteria, implying that DnaE2-provided translesion synthesis partially substitutes the absence of Pol I in cells containing heavily damaged DNA.

  4. File list: Pol.Oth.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.20.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Others S...RX1027436,SRX1027435,SRX1027434,SRX1027433,SRX668218,SRX099880,SRX099879 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Oth.20.RNA_polymerase_II.AllCell.bed ...

  5. File list: Pol.Myo.05.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Myo.05.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Muscle SR.../dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Myo.05.RNA_Polymerase_II.AllCell.bed ...

  6. File list: Pol.YSt.10.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.YSt.10.RNA_Polymerase_II.AllCell sacCer3 RNA polymerase RNA Polymerase II Yeast... strain SRX092435,SRX360917,SRX360914,SRX497380,SRX497382,SRX497381,SRX360915 http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Pol.YSt.10.RNA_Polymerase_II.AllCell.bed ...

  7. File list: Pol.Lar.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lar.05.RNA_polymerase_II.AllCell dm3 RNA polymerase RNA polymerase II Larvae SR...SRX151962,SRX182775,SRX661503,SRX013070,SRX013072,SRX013113,SRX013082,SRX151961 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Pol.Lar.05.RNA_polymerase_II.AllCell.bed ...

  8. File list: Pol.CDV.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.CDV.10.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Cardiova...,SRX080152,SRX080153,SRX367018,SRX367016 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.CDV.10.RNA_polymerase_II.AllCell.bed ...

  9. File list: Pol.Lar.05.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lar.05.RNA_Polymerase_II.AllCell ce10 RNA polymerase RNA Polymerase II Larvae h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Lar.05.RNA_Polymerase_II.AllCell.bed ...

  10. File list: Pol.Bld.20.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.20.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Blood SRX...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.20.RNA_Polymerase_II.AllCell.bed ...

  11. File list: Pol.Epd.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Epd.50.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Epidermi...247,SRX080162,SRX807622 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Epd.50.RNA_polymerase_II.AllCell.bed ...

  12. File list: Pol.Lng.10.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lng.10.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Lung SRX1...43816,SRX062976,SRX020252 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Lng.10.RNA_Polymerase_II.AllCell.bed ...

  13. File list: Pol.Emb.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.10.RNA_polymerase_II.AllCell ce10 RNA polymerase RNA polymerase II Embryo S...,SRX043867 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Emb.10.RNA_polymerase_II.AllCell.bed ...

  14. File list: Pol.Utr.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Utr.05.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Uterus S...SRX573070,SRX027921,SRX1048949,SRX1136641,SRX1136638,SRX099217 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Utr.05.RNA_polymerase_II.AllCell.bed ...

  15. File list: Pol.Neu.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.20.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Neural S...6,SRX743838,SRX743832,SRX743834,SRX743840 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Neu.20.RNA_polymerase_II.AllCell.bed ...

  16. File list: Pol.Plc.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Plc.50.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Placenta... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Plc.50.RNA_polymerase_II.AllCell.bed ...

  17. File list: Pol.Oth.05.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.05.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Others SR...X143827,SRX112963,SRX736456,SRX736457,SRX112981,SRX143834,SRX335666,SRX957689 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Oth.05.RNA_Polymerase_II.AllCell.bed ...

  18. File list: Pol.Emb.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.20.RNA_polymerase_II.AllCell ce10 RNA polymerase RNA polymerase II Embryo S...,SRX043869 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Emb.20.RNA_polymerase_II.AllCell.bed ...

  19. File list: Pol.Gon.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Gon.20.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Gonad ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Gon.20.RNA_polymerase_II.AllCell.bed ...

  20. File list: Pol.Unc.05.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.05.RNA_Polymerase_II.AllCell ce10 RNA polymerase RNA Polymerase II Unclassi...fied http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Unc.05.RNA_Polymerase_II.AllCell.bed ...

  1. File list: Pol.Adp.50.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adp.50.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Adipocyte... SRX800011,SRX800010,SRX341031,SRX341032,SRX341029,SRX800016,SRX800017,SRX341030 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Adp.50.RNA_Polymerase_II.AllCell.bed ...

  2. File list: Pol.ALL.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.ALL.05.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II All cell...,SRX1013886,SRX1013900 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.ALL.05.RNA_polymerase_II.AllCell.bed ...

  3. File list: Pol.CDV.20.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.CDV.20.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Cardiovas...X320034,SRX346170,SRX346169,SRX373605,SRX680476 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.CDV.20.RNA_Polymerase_II.AllCell.bed ...

  4. File list: Pol.Unc.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.05.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Unclassi...fied http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Unc.05.RNA_polymerase_II.AllCell.bed ...

  5. File list: Pol.Spl.10.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Spl.10.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Spleen SR...X062981,SRX143838,SRX020253 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Spl.10.RNA_Polymerase_II.AllCell.bed ...

  6. File list: Pol.Unc.05.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.05.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Unclassif...ied SRX254629 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Unc.05.RNA_Polymerase_II.AllCell.bed ...

  7. File list: Pol.ALL.20.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.ALL.20.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II All cell ...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.ALL.20.RNA_Polymerase_II.AllCell.bed ...

  8. File list: Pol.Unc.10.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.10.RNA_Polymerase_II.AllCell ce10 RNA polymerase RNA Polymerase II Unclassi...fied http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Unc.10.RNA_Polymerase_II.AllCell.bed ...

  9. File list: Pol.Neu.20.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.20.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Neural SR...,SRX685285,SRX217736 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.20.RNA_Polymerase_II.AllCell.bed ...

  10. File list: Pol.Bld.50.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.50.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Blood SRX...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.50.RNA_Polymerase_II.AllCell.bed ...

  11. File list: Pol.Pup.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Pup.10.RNA_polymerase_II.AllCell dm3 RNA polymerase RNA polymerase II Pupae SRX...013069 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Pol.Pup.10.RNA_polymerase_II.AllCell.bed ...

  12. File list: Pol.Emb.50.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.50.RNA_Polymerase_II.AllCell ce10 RNA polymerase RNA Polymerase II Embryo h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Emb.50.RNA_Polymerase_II.AllCell.bed ...

  13. File list: Pol.Unc.20.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.20.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Unclassif...ied SRX254629 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Unc.20.RNA_Polymerase_II.AllCell.bed ...

  14. File list: Pol.Lng.05.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lng.05.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Lung SRX0...62976,SRX143816,SRX020252 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Lng.05.RNA_Polymerase_II.AllCell.bed ...

  15. File list: Pol.Lng.20.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lng.20.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Lung SRX0...62976,SRX143816,SRX020252 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Lng.20.RNA_Polymerase_II.AllCell.bed ...

  16. File list: Pol.Gon.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Gon.50.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Gonad ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Gon.50.RNA_polymerase_II.AllCell.bed ...

  17. File list: Pol.Kid.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Kid.20.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Kidney S...SRX1206072,SRX1206066,SRX326423,SRX1206067,SRX003883,SRX003882,SRX367323 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Kid.20.RNA_polymerase_II.AllCell.bed ...

  18. File list: Pol.Adl.05.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adl.05.RNA_Polymerase_II.AllCell ce10 RNA polymerase RNA Polymerase II Adult SR...SRX1388757,SRX1388756 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Adl.05.RNA_Polymerase_II.AllCell.bed ...

  19. File list: Pol.PSC.50.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.50.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Pluripote...SRX213760,SRX213764 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.PSC.50.RNA_Polymerase_II.AllCell.bed ...

  20. File list: Pol.Epd.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Epd.10.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Epidermi...246,SRX663247,SRX807622 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Epd.10.RNA_polymerase_II.AllCell.bed ...

  1. File list: Pol.Epd.10.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Epd.10.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Epidermis... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Epd.10.RNA_Polymerase_II.AllCell.bed ...

  2. File list: Pol.Brs.10.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Brs.10.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Breast SR...078990 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.10.RNA_Polymerase_II.AllCell.bed ...

  3. File list: Pol.Dig.20.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Dig.20.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Digestive... tract SRX112957,SRX143802 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Dig.20.RNA_Polymerase_II.AllCell.bed ...

  4. File list: Pol.Spl.05.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Spl.05.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Spleen SR...X062981,SRX143838,SRX020253 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Spl.05.RNA_Polymerase_II.AllCell.bed ...

  5. File list: Pol.PSC.20.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.20.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Pluripote...SRX213760,SRX213764 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.PSC.20.RNA_Polymerase_II.AllCell.bed ...

  6. File list: Pol.Pup.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Pup.05.RNA_polymerase_II.AllCell dm3 RNA polymerase RNA polymerase II Pupae SRX...013069 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Pol.Pup.05.RNA_polymerase_II.AllCell.bed ...

  7. File list: Pol.Unc.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.50.RNA_polymerase_II.AllCell ce10 RNA polymerase RNA polymerase II Unclassi...p://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Unc.50.RNA_polymerase_II.AllCell.bed ...

  8. File list: Pol.Plc.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Plc.10.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Placenta... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Plc.10.RNA_polymerase_II.AllCell.bed ...

  9. File list: Pol.Unc.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.05.RNA_polymerase_II.AllCell dm3 RNA polymerase RNA polymerase II Unclassif...ied SRX110774 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Pol.Unc.05.RNA_polymerase_II.AllCell.bed ...

  10. File list: Pol.ALL.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.ALL.05.RNA_polymerase_II.AllCell dm3 RNA polymerase RNA polymerase II All cell ...013077,SRX050604,SRX050605 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Pol.ALL.05.RNA_polymerase_II.AllCell.bed ...

  11. File list: Pol.Adp.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adp.50.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Adipocyt...e SRX682084,SRX682086,SRX682085,SRX682083 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Adp.50.RNA_polymerase_II.AllCell.bed ...

  12. File list: Pol.ALL.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.ALL.10.RNA_polymerase_II.AllCell ce10 RNA polymerase RNA polymerase II All cell...3965,SRX043869,SRX043867,SRX043875,SRX043967,SRX043881,SRX043879 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.ALL.10.RNA_polymerase_II.AllCell.bed ...

  13. File list: Pol.ALL.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.ALL.05.RNA_polymerase_II.AllCell sacCer3 RNA polymerase RNA polymerase II All c...ell types http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Pol.ALL.05.RNA_polymerase_II.AllCell.bed ...

  14. File list: Pol.Emb.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.50.RNA_polymerase_II.AllCell dm3 RNA polymerase RNA polymerase II Embryo SR...7582,SRX050604,SRX050605,SRX013073 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Pol.Emb.50.RNA_polymerase_II.AllCell.bed ...

  15. File list: Pol.Epd.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Epd.20.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Epidermi...248,SRX663247,SRX807622 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Epd.20.RNA_polymerase_II.AllCell.bed ...

  16. File list: Pol.Plc.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Plc.05.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Placenta... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Plc.05.RNA_polymerase_II.AllCell.bed ...

  17. File list: Pol.Unc.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.20.RNA_polymerase_II.AllCell ce10 RNA polymerase RNA polymerase II Unclassi...p://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Unc.20.RNA_polymerase_II.AllCell.bed ...

  18. File list: Pol.Kid.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: Pol.Adl.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Pol.Prs.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Pol.PSC.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: Pol.Utr.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Pol.Adl.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adl.20.RNA_polymerase_II.AllCell ce10 RNA polymerase RNA polymerase II Adult SR...SRX554718,SRX043965,SRX043963,SRX043964 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Adl.20.RNA_polymerase_II.AllCell.bed ...

  4. File list: Pol.Emb.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.05.RNA_polymerase_II.AllCell ce10 RNA polymerase RNA polymerase II Embryo S...,SRX043867 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Emb.05.RNA_polymerase_II.AllCell.bed ...

  5. File list: Pol.Dig.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Dig.05.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Digestiv...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Dig.05.RNA_polymerase_II.AllCell.bed ...

  6. File list: Pol.Neu.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.50.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Neural S...6,SRX743834,SRX743838,SRX743840,SRX743832 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Neu.50.RNA_polymerase_II.AllCell.bed ...

  7. File list: Pol.Emb.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Pol.Liv.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Pol.Prs.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: Pol.Pan.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: Pol.Neu.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: Pol.Lng.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lng.10.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Lung SRX... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Lng.10.RNA_polymerase_II.AllCell.bed ...

  13. File list: Pol.Unc.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.20.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Unclassi...fied http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Unc.20.RNA_polymerase_II.AllCell.bed ...

  14. File list: Pol.Unc.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: Pol.Lar.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: Pol.Prs.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Prs.05.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Prostate...363,SRX173198,SRX173197 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Prs.05.RNA_polymerase_II.AllCell.bed ...

  17. File list: Pol.Bon.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bon.20.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Bone SRX...,SRX351408 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bon.20.RNA_polymerase_II.AllCell.bed ...

  18. File list: Pol.Myo.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: Pol.ALL.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.ALL.20.RNA_polymerase_II.AllCell sacCer3 RNA polymerase RNA polymerase II All c...ell types http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Pol.ALL.20.RNA_polymerase_II.AllCell.bed ...

  20. File list: Pol.Oth.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.50.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Others S...RX1027436,SRX1027435,SRX1027434,SRX1027433,SRX668218,SRX099880,SRX099879 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Oth.50.RNA_polymerase_II.AllCell.bed ...

  1. File list: Pol.Bld.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.50.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Blood SR...,SRX153079,SRX017717,SRX103447,SRX386121,SRX038919,SRX038920,SRX080132 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.50.RNA_polymerase_II.AllCell.bed ...

  2. File list: Pol.Myo.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Myo.10.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Muscle h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Myo.10.RNA_polymerase_II.AllCell.bed ...

  3. File list: Pol.Myo.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Myo.05.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Muscle h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Myo.05.RNA_polymerase_II.AllCell.bed ...

  4. File list: Pol.Emb.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.50.RNA_polymerase_II.AllCell ce10 RNA polymerase RNA polymerase II Embryo S...,SRX043866 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Emb.50.RNA_polymerase_II.AllCell.bed ...

  5. File list: Pol.ALL.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.ALL.10.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II All cell...,SRX1013886,SRX1013900 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.ALL.10.RNA_polymerase_II.AllCell.bed ...

  6. File list: Pol.Liv.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Liv.50.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Liver SR...1013886 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Liv.50.RNA_polymerase_II.AllCell.bed ...

  7. File list: Pol.Kid.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Kid.05.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Kidney S...SRX128201,SRX128200,SRX003882,SRX1206065,SRX1206066,SRX1206067,SRX367323 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Kid.05.RNA_polymerase_II.AllCell.bed ...

  8. File list: Pol.Plc.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Plc.20.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Placenta... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Plc.20.RNA_polymerase_II.AllCell.bed ...

  9. File list: Pol.Pan.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Pan.50.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Pancreas... SRX190244 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Pan.50.RNA_polymerase_II.AllCell.bed ...

  10. File list: Pol.Bon.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bon.10.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Bone SRX...,SRX351408 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bon.10.RNA_polymerase_II.AllCell.bed ...

  11. File list: Pol.Bld.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.10.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Blood SR...,SRX017986,SRX017985,SRX728781,SRX017717,SRX005163,SRX024360,SRX017718 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.10.RNA_polymerase_II.AllCell.bed ...

  12. File list: Pol.Epd.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Epd.05.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Epidermi...245,SRX663247,SRX807622 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Epd.05.RNA_polymerase_II.AllCell.bed ...

  13. File list: Pol.Emb.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.10.RNA_polymerase_II.AllCell dm3 RNA polymerase RNA polymerase II Embryo SR...7582,SRX050604,SRX050605,SRX013077 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Pol.Emb.10.RNA_polymerase_II.AllCell.bed ...

  14. File list: Pol.Myo.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Myo.20.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Muscle h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Myo.20.RNA_polymerase_II.AllCell.bed ...

  15. File list: Pol.ALL.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.ALL.50.RNA_polymerase_II.AllCell dm3 RNA polymerase RNA polymerase II All cell ...050605,SRX013073 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Pol.ALL.50.RNA_polymerase_II.AllCell.bed ...

  16. File list: Pol.Unc.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.10.RNA_polymerase_II.AllCell ce10 RNA polymerase RNA polymerase II Unclassi...p://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Unc.10.RNA_polymerase_II.AllCell.bed ...

  17. File list: Pol.Unc.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.10.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Unclassi...fied http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Unc.10.RNA_polymerase_II.AllCell.bed ...

  18. File list: Pol.PSC.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.05.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Pluripot...833412,SRX149642,SRX702059 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.PSC.05.RNA_polymerase_II.AllCell.bed ...

  19. File list: Pol.Kid.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Kid.50.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Kidney S...SRX1206066,SRX1206067,SRX003882,SRX003883,SRX1206065,SRX367323,SRX326416 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Kid.50.RNA_polymerase_II.AllCell.bed ...

  20. File list: Pol.Unc.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.05.RNA_polymerase_II.AllCell ce10 RNA polymerase RNA polymerase II Unclassi...p://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Unc.05.RNA_polymerase_II.AllCell.bed ...

  1. File list: Pol.Dig.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Dig.50.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Digestiv...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Dig.50.RNA_polymerase_II.AllCell.bed ...

  2. File list: Pol.Prs.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Prs.20.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Prostate...557,SRX173197,SRX173198 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Prs.20.RNA_polymerase_II.AllCell.bed ...

  3. File list: Pol.YSt.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.YSt.20.RNA_polymerase_II.AllCell sacCer3 RNA polymerase RNA polymerase II Yeast... strain http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Pol.YSt.20.RNA_polymerase_II.AllCell.bed ...

  4. File list: Pol.ALL.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.ALL.50.RNA_polymerase_II.AllCell sacCer3 RNA polymerase RNA polymerase II All c...ell types http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Pol.ALL.50.RNA_polymerase_II.AllCell.bed ...

  5. File list: Pol.Lng.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lng.05.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Lung SRX... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Lng.05.RNA_polymerase_II.AllCell.bed ...

  6. File list: Pol.Oth.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.05.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Others S...RX1027435,SRX668218,SRX1027436,SRX1027434,SRX1027433,SRX099879,SRX099880 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Oth.05.RNA_polymerase_II.AllCell.bed ...

  7. File list: Pol.Pan.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Pan.05.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Pancreas... SRX190244 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Pan.05.RNA_polymerase_II.AllCell.bed ...

  8. File list: Pol.Unc.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Unc.50.RNA_polymerase_II.AllCell sacCer3 RNA polymerase RNA polymerase II Uncla...ssified http://dbarchive.biosciencedbc.jp/kyushu-u/sacCer3/assembled/Pol.Unc.50.RNA_polymerase_II.AllCell.bed ...

  9. File list: Pol.Lng.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lng.50.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Lung SRX... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Lng.50.RNA_polymerase_II.AllCell.bed ...

  10. File list: Pol.Dig.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Dig.10.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Digestiv...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Dig.10.RNA_polymerase_II.AllCell.bed ...

  11. File list: Pol.ALL.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.ALL.10.RNA_polymerase_II.AllCell dm3 RNA polymerase RNA polymerase II All cell ...050604,SRX050605,SRX013077 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Pol.ALL.10.RNA_polymerase_II.AllCell.bed ...

  12. File list: Pol.CDV.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.CDV.20.RNA_polymerase_II.AllCell hg19 RNA polymerase RNA polymerase II Cardiova...,SRX346933,SRX346936,SRX367018,SRX367016 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.CDV.20.RNA_polymerase_II.AllCell.bed ...

  13. Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass.

    Science.gov (United States)

    Lee, Young-Sam; Gregory, Mark T; Yang, Wei

    2014-02-25

    DNA polymerase ζ (Pol ζ) is a eukaryotic B-family DNA polymerase that specializes in translesion synthesis and is essential for normal embryogenesis. At a minimum, Pol ζ consists of a catalytic subunit Rev3 and an accessory subunit Rev7. Mammalian Rev3 contains >3,000 residues and is twice as large as the yeast homolog. To date, no vertebrate Pol ζ has been purified for biochemical characterization. Here we report purification of a series of human Rev3 deletion constructs expressed in HEK293 cells and identification of a minimally catalytically active human Pol ζ variant. With a tagged form of an active Pol ζ variant, we isolated two additional accessory subunits of human Pol ζ, PolD2 and PolD3. The purified four-subunit Pol ζ4 (Rev3-Rev7-PolD2-PolD3) is much more efficient and more processive at bypassing a 1,2-intrastrand d(GpG)-cisplatin cross-link than the two-subunit Pol ζ2 (Rev3-Rev7). We show that complete bypass of cisplatin lesions requires Pol η to insert dCTP opposite the 3' guanine and Pol ζ4 to extend the primers.

  14. Human PrimPol activity is enhanced by RPA.

    Science.gov (United States)

    Martínez-Jiménez, María I; Lahera, Antonio; Blanco, Luis

    2017-04-10

    Human PrimPol is a primase belonging to the AEP superfamily with the unique ability to synthesize DNA primers de novo, and a non-processive DNA polymerase able to bypass certain DNA lesions. PrimPol facilitates both mitochondrial and nuclear replication fork progression either acting as a conventional TLS polymerase, or repriming downstream of blocking lesions. In vivo assays have shown that PrimPol is rapidly recruited to sites of DNA damage by interaction with the human replication protein A (RPA). In agreement with previous findings, we show here that the higher affinity of RPA for ssDNA inhibits PrimPol activities in short ssDNA templates. In contrast, once the amount of ssDNA increases up to a length in which both proteins can simultaneously bind ssDNA, as expected during replicative stress conditions, PrimPol and RPA functionally interact, and their binding capacities are mutually enhanced. When using M13 ssDNA as template, RPA stimulated both the primase and polymerase activities of PrimPol, either alone or in synergy with Polε. These new findings supports the existence of a functional PrimPol/RPA association that allows repriming at the exposed ssDNA regions formed in the leading strand upon replicase stalling.

  15. Mitotic Transcriptional Activation: Clearance of Actively Engaged Pol II via Transcriptional Elongation Control in Mitosis.

    Science.gov (United States)

    Liang, Kaiwei; Woodfin, Ashley R; Slaughter, Brian D; Unruh, Jay R; Box, Andrew C; Rickels, Ryan A; Gao, Xin; Haug, Jeffrey S; Jaspersen, Sue L; Shilatifard, Ali

    2015-11-05

    Although it is established that some general transcription factors are inactivated at mitosis, many details of mitotic transcription inhibition (MTI) and its underlying mechanisms are largely unknown. We have identified mitotic transcriptional activation (MTA) as a key regulatory step to control transcription in mitosis for genes with transcriptionally engaged RNA polymerase II (Pol II) to activate and transcribe until the end of the gene to clear Pol II from mitotic chromatin, followed by global impairment of transcription reinitiation through MTI. Global nascent RNA sequencing and RNA fluorescence in situ hybridization demonstrate the existence of transcriptionally engaged Pol II in early mitosis. Both genetic and chemical inhibition of P-TEFb in mitosis lead to delays in the progression of cell division. Together, our study reveals a mechanism for MTA and MTI whereby transcriptionally engaged Pol II can progress into productive elongation and finish transcription to allow proper cellular division. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. File list: Pol.CeL.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: Pol.NoD.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: Pol.EmF.05.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: Pol.NoD.05.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Pol.NoD.10.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Pol.NoD.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: Pol.NoD.05.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Pol.NoD.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: Pol.NoD.50.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: Pol.NoD.10.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: Pol.CeL.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: Pol.NoD.20.RNA_polymerase_II.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. Observatorio de Política Internacional II. AMERICAS - Ecuador. Política y fútbol

    OpenAIRE

    Neira Fernández, Enrique

    2007-01-01

    Observatorio de Política Internacional II. AMÉRICAS (Neira Fernández, Enrique) RECIENTES Año 2008 Nicaragua. Un remedo revolucionario Bolivia. ¿Una o dislocada? Paraguay. El ex obispo presidente Perú. El rojo sangre de sendero luminoso Estados Unidos. Panorama tras las elecciones primarias RECIENTES Año 2007 Argentina. Contundente triunfo de Cristina Fernández Bolivia. Nuevos rumbos ¡no más embrollo! Ecuador. Nueva constitución, nuevo rumbo Guatemala....

  9. Murine mammary tumor virus pol-related sequences in human DNA: characterization and sequence comparison with the complete murine mammary tumor virus pol gene

    International Nuclear Information System (INIS)

    Deen, K.C.; Sweet, R.W.

    1986-01-01

    Sequences in the human genome with homology to the murine mammary tumor virus (MMTV) pol gene were isolated from a human phage library. Ten clones with extensive pol homology were shown to define five separate loci. These loci share common sequences immediately adjacent to the pol-like segments and, in addition, contain a related repeat element which bounds this region. This organization is suggestive of a proviral structure. The authors estimate that the human genome contains 30 to 40 copies of these pol-related sequences. The pol region of one of the cloned segments (HM16) and the complete MMTV pol gene were sequenced and compared. The nucleotide homology between these pol sequences is 52% and is concentrated in the terminal regions. The MMTV pol gene contains a single long open reading frame encoding 899 amino acids and is demarcated from the partially overlapping putative gag gene by termination codons and a shift in translational reading frame. The pol sequence of HM16 is multiply terminated but does contain open reading frames which encode 370, 105, and 112 amino acids residues in separate reading frames. The authors deduced a composite pol protein sequence for HM16 by aligning it to the MMTV pol gene and then compared these sequences with other retroviral pol protein sequences. Conserved sequences occur in both the amino and carboxyl regions which lie within the polymerase and endonuclease domains of pol, respectively

  10. Promoter2.0: for the recognition of PolII promoter sequences

    DEFF Research Database (Denmark)

    Knudsen, Steen; Knudsen, Steen

    1999-01-01

    Motivation : A new approach to the prediction of eukaryotic PolII promoters from DNA sequence takesadvantage of a combination of elements similar to neural networks and genetic algorithms to recognize a set ofdiscrete subpatterns with variable separation as one pattern: a promoter. The neural...... of optimization, the algorithm was able todiscriminate between vertebrate promoter and non-promoter sequences in a test set with a correlationcoefficient of 0.63. In addition, all five known transcription start sites on the plus strand of the completeadenovirus genome were within 161 bp of 35 predicted...

  11. Observatorio de Política Internacional II. AMERICAS - Elecciones en U.S.A.

    OpenAIRE

    Neira Fernández, Enrique

    2007-01-01

    Observatorio de Política Internacional II. AMÉRICAS (Neira Fernández, Enrique) RECIENTES Año 2008 Nicaragua. Un remedo revolucionario Bolivia. ¿Una o dislocada? Paraguay. El ex obispo presidente Perú. El rojo sangre de sendero luminoso Estados Unidos. Panorama tras las elecciones primarias RECIENTES Año 2007 Argentina. Contundente triunfo de Cristina Fernández Bolivia. Nuevos rumbos ¡no más embrollo! Ecuador. Nueva constitución, nuevo rumbo Guatemala....

  12. Arabidopsis Pol II-Dependent in Vitro Transcription System Reveals Role of Chromatin for Light-Inducible rbcS Gene Transcription1

    Science.gov (United States)

    Ido, Ayaka; Iwata, Shinya; Iwata, Yuka; Igarashi, Hisako; Hamada, Takahiro; Sonobe, Seiji; Sugiura, Masahiro; Yukawa, Yasushi

    2016-01-01

    In vitro transcription is an essential tool to study the molecular mechanisms of transcription. For over a decade, we have developed an in vitro transcription system from tobacco (Nicotiana tabacum)-cultured cells (BY-2), and this system supported the basic activities of the three RNA polymerases (Pol I, Pol II, and Pol III). However, it was not suitable to study photosynthetic genes, because BY-2 cells have lost their photosynthetic activity. Therefore, Arabidopsis (Arabidopsis thaliana) in vitro transcription systems were developed from green and etiolated suspension cells. Sufficient in vitro Pol II activity was detected after the minor modification of the nuclear soluble extracts preparation method; removal of vacuoles from protoplasts and L-ascorbic acid supplementation in the extraction buffer were particularly effective. Surprisingly, all four Arabidopsis Rubisco small subunit (rbcS-1A, rbcS-1B, rbcS-2B, and rbcS-3B) gene members were in vitro transcribed from the naked DNA templates without any light-dependent manner. However, clear light-inducible transcriptions were observed using chromatin template of rbcS-1A gene, which was prepared with a human nucleosome assembly protein 1 (hNAP1) and HeLa histones. This suggested that a key determinant of light-dependency through the rbcS gene transcription was a higher order of DNA structure (i.e. chromatin). PMID:26662274

  13. Pol II promoter prediction using characteristic 4-mer motifs: a machine learning approach

    Directory of Open Access Journals (Sweden)

    Shoyaib Mohammad

    2008-10-01

    Full Text Available Abstract Background Eukaryotic promoter prediction using computational analysis techniques is one of the most difficult jobs in computational genomics that is essential for constructing and understanding genetic regulatory networks. The increased availability of sequence data for various eukaryotic organisms in recent years has necessitated for better tools and techniques for the prediction and analysis of promoters in eukaryotic sequences. Many promoter prediction methods and tools have been developed to date but they have yet to provide acceptable predictive performance. One obvious criteria to improve on current methods is to devise a better system for selecting appropriate features of promoters that distinguish them from non-promoters. Secondly improved performance can be achieved by enhancing the predictive ability of the machine learning algorithms used. Results In this paper, a novel approach is presented in which 128 4-mer motifs in conjunction with a non-linear machine-learning algorithm utilising a Support Vector Machine (SVM are used to distinguish between promoter and non-promoter DNA sequences. By applying this approach to plant, Drosophila, human, mouse and rat sequences, the classification model has showed 7-fold cross-validation percentage accuracies of 83.81%, 94.82%, 91.25%, 90.77% and 82.35% respectively. The high sensitivity and specificity value of 0.86 and 0.90 for plant; 0.96 and 0.92 for Drosophila; 0.88 and 0.92 for human; 0.78 and 0.84 for mouse and 0.82 and 0.80 for rat demonstrate that this technique is less prone to false positive results and exhibits better performance than many other tools. Moreover, this model successfully identifies location of promoter using TATA weight matrix. Conclusion The high sensitivity and specificity indicate that 4-mer frequencies in conjunction with supervised machine-learning methods can be beneficial in the identification of RNA pol II promoters comparative to other methods. This

  14. RNA Pol II promotes transcription of centromeric satellite DNA in beetles.

    Directory of Open Access Journals (Sweden)

    Zeljka Pezer

    Full Text Available Transcripts of centromeric satellite DNAs are known to play a role in heterochromatin formation as well as in establishment of the kinetochore. However, little is known about basic mechanisms of satellite DNA expression within constitutive heterochromatin and its regulation. Here we present comprehensive analysis of transcription of abundant centromeric satellite DNA, PRAT from beetle Palorus ratzeburgii (Coleoptera. This satellite is characterized by preservation and extreme sequence conservation among evolutionarily distant insect species. PRAT is expressed in all three developmental stages: larvae, pupae and adults at similar level. Transcripts are abundant comprising 0.033% of total RNA and are heterogeneous in size ranging from 0.5 kb up to more than 5 kb. Transcription proceeds from both strands but with 10 fold different expression intensity and transcripts are not processed into siRNAs. Most of the transcripts (80% are not polyadenylated and remain in the nucleus while a small portion is exported to the cytoplasm. Multiple, irregularly distributed transcription initiation sites as well as termination sites have been mapped within the PRAT sequence using primer extension and RLM-RACE. The presence of cap structure as well as poly(A tails in a portion of the transcripts indicate RNA polymerase II-dependent transcription and a putative polymerase II promoter site overlaps the most conserved part of the PRAT sequence. The treatment of larvae with alpha-amanitin decreases the level of PRAT transcripts at concentrations that selectively inhibit pol II activity. In conclusion, stable, RNA polymerase II dependant transcripts of abundant centromeric satellite DNA, not regulated by RNAi, have been identified and characterized. This study offers a basic understanding of expression of highly abundant heterochromatic DNA which in beetle species constitutes up to 50% of the genome.

  15. DNA-binding determinants promoting NHEJ by human Polμ.

    Science.gov (United States)

    Martin, Maria Jose; Juarez, Raquel; Blanco, Luis

    2012-12-01

    Non-homologous end-joining (NHEJ), the preferred pathway to repair double-strand breaks (DSBs) in higher eukaryotes, relies on a collection of molecular tools to process the broken ends, including specific DNA polymerases. Among them, Polµ is unique as it can catalyze DNA synthesis upon connection of two non-complementary ends. Here, we demonstrate that this capacity is intrinsic to Polµ, not conferred by other NHEJ factors. To understand the molecular determinants of its specific function in NHEJ, the interaction of human Polµ with DNA has been directly visualized by electromobility shift assay and footprinting assays. Stable interaction with a DNA gap requires the presence of a recessive 5'-P, thus orienting the catalytic domain for primer and nucleotide binding. Accordingly, recognition of the 5'-P is crucial to align the two DNA substrates of the NHEJ reaction. Site-directed mutagenesis demonstrates the relevance of three specific residues (Lys(249), Arg(253) and Arg(416)) in stabilizing the primer strand during end synapsis, allowing a range of microhomology-induced distortions beneficial for NHEJ. Moreover, our results suggest that the Polµ BRCT domain, thought to be exclusively involved in interaction with NHEJ core factors, has a direct role in binding the DNA region neighbor to the 5'-P, thus boosting Polµ-mediated NHEJ reactions.

  16. Explosive mutation accumulation triggered by heterozygous human Pol ε proofreading-deficiency is driven by suppression of mismatch repair

    Science.gov (United States)

    Campbell, Brittany B; Ungerleider, Nathan; Light, Nicholas; Wu, Tong; LeCompte, Kimberly G; Goksenin, A Yasemin; Bunnell, Bruce A; Tabori, Uri; Shlien, Adam

    2018-01-01

    Tumors defective for DNA polymerase (Pol) ε proofreading have the highest tumor mutation burden identified. A major unanswered question is whether loss of Pol ε proofreading by itself is sufficient to drive this mutagenesis, or whether additional factors are necessary. To address this, we used a combination of next generation sequencing and in vitro biochemistry on human cell lines engineered to have defects in Pol ε proofreading and mismatch repair. Absent mismatch repair, monoallelic Pol ε proofreading deficiency caused a rapid increase in a unique mutation signature, similar to that observed in tumors from patients with biallelic mismatch repair deficiency and heterozygous Pol ε mutations. Restoring mismatch repair was sufficient to suppress the explosive mutation accumulation. These results strongly suggest that concomitant suppression of mismatch repair, a hallmark of colorectal and other aggressive cancers, is a critical force for driving the explosive mutagenesis seen in tumors expressing exonuclease-deficient Pol ε. PMID:29488881

  17. Evidence that Mediator is essential for Pol II transcription, but is not a required component of the preinitiation complex in vivo.

    Science.gov (United States)

    Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin

    2017-07-12

    The Mediator complex has been described as a general transcription factor, but it is unclear if it is essential for Pol II transcription and/or is a required component of the preinitiation complex (PIC) in vivo. Here, we show that depletion of individual subunits, even those essential for cell growth, causes a general but only modest decrease in transcription. In contrast, simultaneous depletion of all Mediator modules causes a drastic decrease in transcription. Depletion of head or middle subunits, but not tail subunits, causes a downstream shift in the Pol II occupancy profile, suggesting that Mediator at the core promoter inhibits promoter escape. Interestingly, a functional PIC and Pol II transcription can occur when Mediator is not detected at core promoters. These results provide strong evidence that Mediator is essential for Pol II transcription and stimulates PIC formation, but it is not a required component of the PIC in vivo.

  18. Replication restart in UV-irradiated Escherichia coli involving pols II, III, V, PriA, RecA and RecFOR proteins.

    Science.gov (United States)

    Rangarajan, Savithri; Woodgate, Roger; Goodman, Myron F

    2002-02-01

    In Escherichia coli, UV-irradiated cells resume DNA synthesis after a transient inhibition by a process called replication restart. To elucidate the role of several key proteins involved in this process, we have analysed the time dependence of replication restart in strains carrying a combination of mutations in lexA, recA, polB (pol II), umuDC (pol V), priA, dnaC, recF, recO or recR. We find that both pol II and the origin-independent primosome-assembling function of PriA are essential for the immediate recovery of DNA synthesis after UV irradiation. In their absence, translesion replication or 'replication readthrough' occurs approximately 50 min after UV and is pol V-dependent. In a wild-type, lexA+ background, mutations in recF, recO or recR block both pathways. Similar results were obtained with a lexA(Def) recF strain. However, lexA(Def) recO or lexA(Def) recR strains, although unable to facilitate PriA-pol II-dependent restart, were able to perform pol V-dependent readthrough. The defects in restart attributed to mutations in recF, recO or recR were suppressed in a recA730 lexA(Def) strain expressing constitutively activated RecA (RecA*). Our data suggest that in a wild-type background, RecF, O and R are important for the induction of the SOS response and the formation of RecA*-dependent recombination intermediates necessary for PriA/Pol II-dependent replication restart. In con-trast, only RecF is required for the activation of RecA that leads to the formation of pol V (UmuD'2C) and facilitates replication readthrough.

  19. Los grandes, el poder y la cultura política de la nobleza en el reinado de Carlos II

    Directory of Open Access Journals (Sweden)

    Adolfo CARRASCO MARTÍNEZ

    2009-12-01

    Full Text Available RESUMEN: Este artículo se centra en los comportamientos políticos de la aristocracia española durante el reinado de Carlos II. Se estudian las actitudes colectivas del grupo y la evolución de la cultura política nobiliaria en el contexto de las profundas transformaciones que el ejercicio del poder experimentó en el periodo. Grandes y títulos hubieron de dar respuesta a la sucesión de escenarios políticos y, al mismo tiempo, influyeron decisivamente en la marcha de los asuntos. El progresivo deterioro de la autoridad regia determinó el paso a una poliarquía, a un modelo de múltiples centros de poder de equilibrios precarios que reflejaba el debate sobre el absolutismo y la participación política de la alta nobleza. Factores externos, como la cuestión sucesoria y la injerencia de las potencias extranjeras, y factores internos, como la incapacidad nobiliaria de cohesionarse en un proyecto común, la esperanza en liderazgos imposibles y las limitaciones de su cultura política, produjeron la rápida degeneración de la poliarquía en un régimen caótico en el crepúsculo del siglo XVII.ABSTRACT: This paper is focused on the political behaviour of the Spanish aristocracy under the reign of Charles II. It examines the group's general attitudes and the evolution of the noble political consciousness in a context where the exercise of power underwent deep changes. Grandees and titles had to react towards the series of political scenes and at the same time, they decisively had an influence over the course of events. The progressive impairment of the royal authority gave place to a polyarchy, a model of manifold control centres of precarious balance, which reflected the debate between the absolutism and the upper nobility's political concern. External factors, such as successory matters and foreign countries interference, and internal factors, like the noble inability to integrate themselves into a common project, the expectation around

  20. El proyecto neoliberal del rey Abdallah II. para Jordania: zonas francas y política exterior

    OpenAIRE

    Rodríguez Mojica, Erika Liliana

    2016-01-01

    Esta monografía busca explicar los intereses y resultados parciales obtenidos por la monarquía del Reino Hachemí de Jordania en el proyecto neoliberal de apertura económica y creación de zonas francas bajo el gobierno de Abdallah II., especialmente la región fronteriza de Al-Karameh y la relación bilateral con Irak, como parte de su política económica nacional e internacional. Para el análisis se utilizarán dos teorías de Relaciones Internacionales; la teoría de interdependencia compleja de R...

  1. Role for the MED21-MED7 Hinge in Assembly of the Mediator-RNA Polymerase II Holoenzyme*

    Science.gov (United States)

    Sato, Shigeo; Tomomori-Sato, Chieri; Tsai, Kuang-Lei; Yu, Xiaodi; Sardiu, Mihaela; Saraf, Anita; Washburn, Michael P.; Florens, Laurence; Asturias, Francisco J.; Conaway, Ronald C.

    2016-01-01

    Mediator plays an integral role in activation of RNA polymerase II (Pol II) transcription. A key step in activation is binding of Mediator to Pol II to form the Mediator-Pol II holoenzyme. Here, we exploit a combination of biochemistry and macromolecular EM to investigate holoenzyme assembly. We identify a subset of human Mediator head module subunits that bind Pol II independent of other subunits and thus probably contribute to a major Pol II binding site. In addition, we show that binding of human Mediator to Pol II depends on the integrity of a conserved “hinge” in the middle module MED21-MED7 heterodimer. Point mutations in the hinge region leave core Mediator intact but lead to increased disorder of the middle module and markedly reduced affinity for Pol II. These findings highlight the importance of Mediator conformation for holoenzyme assembly. PMID:27821593

  2. Promoter2.0: for the recognition of PolII promoter sequences

    DEFF Research Database (Denmark)

    Knudsen, Steen; Knudsen, Steen

    1999-01-01

    transcription start sites. On standardized test setsconsisting of human genomic DNA, the performance of Promoter2.0 compares well with other softwaredeveloped for the same purpose. Availability : Promoter2.0 is available as a Web server at http://www.cbs.dtu.dk/services/promoter/ Contact : steen@cbs.dtu.dk...

  3. DNA damage regulates alternative splicing through changes in POL II elongation

    International Nuclear Information System (INIS)

    Munoz, M.J.; Perez Santangelo, M.S.; De la Mata, M.; Kornblihtt, A.R.

    2008-01-01

    Many apoptotic genes are regulated via alternative splicing (AS) but little is known about the mechanisms controlling AS in stress situations derived from DNA damage. Here we show that ultraviolet (UV) radiation affects co-transcriptional, but not post transcriptional, AS through a systemic mechanism involving a CDK-9-dependent hyper phosphorylation of RNA polymerase II carboxy terminal domain (CTD) and a subsequent and unprecedented inhibition of transcriptional elongation, estimated in vivo and in real time by FRAP. To mimic this hyper phosphorylation we used CTD mutants with serines 2 or 5 substituted by glutamic acids and found that they not only display lower elongation rates but duplicate the effects of UV light on AS in the absence of irradiation. Consistently, substitution of the serines with alanines prevents the UV effect on splicing. These results represent the first in vivo proof of modulation of elongation in response to an environmental signal, affecting in turn the kinetic coupling between transcription and splicing. (authors)

  4. The SOS and RpoS Regulons Contribute to Bacterial Cell Robustness to Genotoxic Stress by Synergistically Regulating DNA Polymerase Pol II.

    Science.gov (United States)

    Dapa, Tanja; Fleurier, Sébastien; Bredeche, Marie-Florence; Matic, Ivan

    2017-07-01

    Mitomycin C (MMC) is a genotoxic agent that induces DNA cross-links, DNA alkylation, and the production of reactive oxygen species (ROS). MMC induces the SOS response and RpoS regulons in Escherichia coli SOS-encoded functions are required for DNA repair, whereas the RpoS regulon is typically induced by metabolic stresses that slow growth. Thus, induction of the RpoS regulon by MMC may be coincidental, because DNA damage slows growth; alternatively, the RpoS regulon may be an adaptive response contributing to cell survival. In this study, we show that the RpoS regulon is primarily induced by MMC-induced ROS production. We also show that RpoS regulon induction is required for the survival of MMC-treated growing cells. The major contributor to RpoS-dependent resistance to MMC treatment is DNA polymerase Pol II, which is encoded by the polB gene belonging to the SOS regulon. The observation that polB gene expression is controlled by the two major stress response regulons that are required to maximize survival and fitness further emphasizes the key role of this DNA polymerase as an important factor in genome stability. Copyright © 2017 by the Genetics Society of America.

  5. Autoridades locales y partidos políticos en Andalucía durante la II República

    Directory of Open Access Journals (Sweden)

    OCTAVIO RUIZ MANJÓN

    1979-01-01

    Full Text Available Se presenta una tentativa de análisis del comportamiento de los gobernadores provinciales andaluces en su relación con las organizaciones políticas locales entre los años 1931 y 1936. Se establecen vínculos entre tales comportamientos y la sucesión de eventos políticos nacionales y locales. Para ello se emplea la información disponible en la Gaceta de Madrid (el órgano oficial español de la administración pública, así como recortes de la prensa local procedente de las ochos provincias andaluzas. Se analiza la estabilidad de los gobiernos en el ejercicio de sus responsabilidades mediante la comparación del promedio general presentado por cada provincia. Se comparan las fluctuaciones entre los porcentajes con las fluctuaciones generales que tienen lugar en la vida política en cada período considerado. Se concluye que la vida política local, su estructura organizativa y los sucesos que en ella acaecen tienen escasa influencia en la elección y estabilidad de los gobernantes.

  6. Reexamination of human T cell lymphotropic virus (HTLV-I/II) prevalence.

    Science.gov (United States)

    Zucker-Franklin, D; Pancake, B A; Marmor, M; Legler, P M

    1997-06-10

    In the United States, blood donors are being screened for infection with human T cell lymphotropic viruses I and II (HTLV-I/II) by serologic means, which detect antibodies to the structural proteins of these viruses. Because patients with mycosis fungoides (MF) usually do not have such antibodies even though their cells harbor HTLV-I Tax and/or pol proviral sequences, it was questioned whether the prevalence of HTLV infection among healthy blood donors may also be underestimated by current means of testing. To examine this possibility, a study on specimens of relatives of mycosis fungoides patients (MFR) was begun. In addition, to collect data more expeditiously, a cohort of former injection drug users (IDUs) was tested by routine serologic methods, as well as by PCR/Southern blot analysis for Tax, pol, and gag proviral sequences and Western blot analysis for antibodies to the Tax gene product. To date, 6/8 MFRs and 42/81 (51.8%) of HIV-negative IDUs proved to be positive for HTLV, whereas routine serology identified none of the MFR and only 18/81 (22.2%) of the IDUs. Among the latter test subjects, the incidence of HTLV-I also proved to be 10 times higher than expected. Therefore, it is likely that among healthy blood donors infection with HTLV-I/II is more prevalent than is currently assumed. Since Tax is the transforming sequence of HTLV-I/II, testing for Tax sequences and antibodies to its gene product may be desirable in blood transfusion and tissue donor facilities.

  7. Reexamination of human T cell lymphotropic virus (HTLV-I/II) prevalence

    Science.gov (United States)

    Zucker-Franklin, Dorothea; Pancake, Bette A.; Marmor, Michael; Legler, Patricia M.

    1997-01-01

    In the United States, blood donors are being screened for infection with human T cell lymphotropic viruses I and II (HTLV-I/II) by serologic means, which detect antibodies to the structural proteins of these viruses. Because patients with mycosis fungoides (MF) usually do not have such antibodies even though their cells harbor HTLV-I Tax and/or pol proviral sequences, it was questioned whether the prevalence of HTLV infection among healthy blood donors may also be underestimated by current means of testing. To examine this possibility, a study on specimens of relatives of mycosis fungoides patients (MFR) was begun. In addition, to collect data more expeditiously, a cohort of former injection drug users (IDUs) was tested by routine serologic methods, as well as by PCR/Southern blot analysis for Tax, pol, and gag proviral sequences and Western blot analysis for antibodies to the Tax gene product. To date, 6/8 MFRs and 42/81 (51.8%) of HIV-negative IDUs proved to be positive for HTLV, whereas routine serology identified none of the MFR and only 18/81 (22.2%) of the IDUs. Among the latter test subjects, the incidence of HTLV-I also proved to be 10 times higher than expected. Therefore, it is likely that among healthy blood donors infection with HTLV-I/II is more prevalent than is currently assumed. Since Tax is the transforming sequence of HTLV-I/II, testing for Tax sequences and antibodies to its gene product may be desirable in blood transfusion and tissue donor facilities. PMID:9177230

  8. Eco RI RFLP in the human IGF II gene

    Energy Technology Data Exchange (ETDEWEB)

    Cocozza, S; Garofalo, S; Robledo, R; Monticelli, A; Conti, A; Chiarotti, L; Frunzio, R; Bruni, C B; Varrone, S

    1988-03-25

    The probe was a 500 bp cDNA containing exons 2-3 and 4 of the human IGF II gene. The clone was isolated by screening a human liver cDNA library with synthetic oligonucleotides. Eco RI digestion of genomic DNA and hybridization with the IGF II probe detects a two allele polymorphism with allelic fragments of 13.5 kb and 10.5 kb. The frequency was studied 38 unrelated Caucasians: Human IGF II gene was localized on the short arm of chromosome 11 (p15) by in situ hybridization. Codominant segregation was observed in 2 Caucasian families (10 individuals).

  9. IGF-II receptors and IGF-II-stimulated glucose transport in human fat cells

    International Nuclear Information System (INIS)

    Sinha, M.K.; Buchanan, C.; Raineri-Maldonado, C.; Khazanie, P.; Atkinson, S.; DiMarchi, R.; Caro, J.F.

    1990-01-01

    Insulin-like growth factor II (IGF-II) receptors have been described in rat but not in human adipocytes. In both species, IGF-II has been reported to stimulate glucose transport by interacting with the insulin receptor. In this study, we have unequivocally demonstrated the presence of IGF-II receptors in human adipocytes. 125I-labeled IGF-II specifically binds to intact adipocytes, membranes, and lectin-purified detergent solubilized extracts. Through the use of 0.5 mM disuccinimidyl suberate, 125I-IGF-II is cross-linked to a 260-kDa protein that is identified as the IGF-II receptor by displacement experiments with unlabeled IGF-II, IGF-I, and insulin and either by immunoprecipitation or by Western blot analysis with mannose 6-phosphate receptor antibodies. The concentrations of IGF-II required for half-maximal and maximal stimulation of glucose transport in human adipocytes are 35 and 100 times more than that of insulin. The possibility of IGF-II stimulating glucose transport by interacting predominantly with the insulin receptor is suggested by the following: (1) the concentration of IGF-II that inhibits half of insulin binding is only 20 times more than that of insulin; (2) the lack of an additive effect of IGF-II and insulin for maximal stimulation of glucose transport; (3) the ability of monoclonal insulin receptor antibodies to decrease glucose transport stimulated by submaximal concentrations of both IGF-II and insulin; and (4) the ability of IGF-II to stimulate insulin receptor autophosphorylation albeit at a reduced potency when compared with insulin

  10. The World War II Era and Human Rights Education

    Science.gov (United States)

    Waters, Stewart; Russell, William B., III

    2012-01-01

    International revulsion at the violation of human rights during World War II helped spark a global movement to define and protect individual human rights. Starting with the creation of war crimes tribunals after the war, this newfound awareness stimulated a concerted international effort to establish human rights for all, both in periods of war…

  11. Reproduction (II): Human Control of Reproductive Processes

    Science.gov (United States)

    Jost, Alfred

    1970-01-01

    Describes methods of intervening in reproduction of animals and humans (artificial insemination, contraception, ovular and blastodisc transplants, pre selection of sex, cloning) and discusses the social implications of their use with humans. (AL)

  12. Angiotensin II attenuates the natriuresis of water immersion in humans

    DEFF Research Database (Denmark)

    Schou, Morten; Gabrielsen, Anders; Bruun, Niels Eske

    2002-01-01

    The hypothesis was tested that suppression of generation of ANG II is one of the mechanisms of the water immersion (WI)-induced natriuresis in humans. In one protocol, eight healthy young males were subjected to 3 h of 1) WI (WI + placebo), 2) WI combined with ANG II infusion of 0.5 ng. kg(-1). min...

  13. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...

  14. Spectroscopic characterization of furosemide binding to human carbonic anhydrase II.

    Science.gov (United States)

    Ranjbar, Samira; Ghobadi, Sirous; Khodarahmi, Reza; Nemati, Houshang

    2012-05-01

    This study reports the interaction between furosemide and human carbonic anhydrase II (hCA II) using fluorescence, UV-vis and circular dichroism (CD) spectroscopy. Fluorescence data indicated that furosemide quenches the intrinsic fluorescence of the enzyme via a static mechanism and hydrogen bonding and van der Walls interactions play the major role in the drug binding. The binding average distance between furosemide and hCA II was estimated on the basis of the theory of Förster energy transfer. Decrease of protein surface hydrophobicity was also documented upon furosemide binding. Chemical modification of hCA II using N-bromosuccinimide indicated decrease of the number of accessible tryptophans in the presence of furosemide. CD results suggested the occurance of some alterations in α-helical content as well as tertiary structure of hCA II upon drug binding. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

    International Nuclear Information System (INIS)

    Ramasharma, K.; Li, C.H.

    1987-01-01

    Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and α-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin

  16. Molecular cloning of the human casein kinase II α subunit

    International Nuclear Information System (INIS)

    Meisner, H.; Heller-Harrison, R.; Buxton, J.; Czech, M.P.

    1989-01-01

    A human cDNA encoding the α subunit of casein kinase II and a partial cDNA encoding the rat homologue were isolated by using a Drosophila casein kinase II cDNA probe. The 2.2-kb human cDNA contains a 1.2-kb open reading frame, 150 nucleotides of 5' leader, and 850 nucleotides of 3' noncoding region. Except for the first 7 deduced amino acids that are missing in the rat cDNA, the 328 amino acids beginning with the amino terminus are identical between human and rat. The Drosophila enzyme sequence is 90% identical with the human casein kinase II sequence, and there is only a single amino acid difference between the published partial bovine sequence and the human sequence. In addition, the C-terminus of the human cDNA has an extra 53 amino acids not present in Drosophila. Northern analysis of rat and human RNA showed predominant bands of 5.5, 3.1, and 1.8 kb. In rat tissues, brain and spleen had the highest levels of casein kinase II α subunit specific RNA, while skeletal muscle showed the lowest. Southern analysis of human cultured cell and tissue genomic DNA using the full-length cDNA probe revealed two bands with restriction enzymes that have no recognition sites within the cDNA and three to six bands with enzymes having single internal sites. These results are consistent with the possibility that two genes encode the α subunits

  17. Global gene expression analysis of fission yeast mutants impaired in Ser-2 phosphorylation of the RNA pol II carboxy terminal domain.

    Directory of Open Access Journals (Sweden)

    Reza Saberianfar

    Full Text Available In Schizosaccharomyces pombe the nuclear-localized Lsk1p-Lsc1p cyclin dependent kinase complex promotes Ser-2 phosphorylation of the heptad repeats found within the RNA pol II carboxy terminal domain (CTD. Here, we first provide evidence supporting the existence of a third previously uncharacterized Ser-2 CTD kinase subunit, Lsg1p. As expected for a component of the complex, Lsg1p localizes to the nucleus, promotes Ser-2 phosphorylation of the CTD, and physically interacts with both Lsk1p and Lsc1p in vivo. Interestingly, we also demonstrate that lsg1Δ mutants--just like lsk1Δ and lsc1Δ strains--are compromised in their ability to faithfully and reliably complete cytokinesis. Next, to address whether kinase mediated alterations in CTD phosphorylation might selectively alter the expression of genes with roles in cytokinesis and/or the cytoskeleton, global gene expression profiles were analyzed. Mutants impaired in Ser-2 phosphorylation display little change with respect to the level of transcription of most genes. However, genes affecting cytokinesis--including the actin interacting protein gene, aip1--as well as genes with roles in meiosis, are included in a small subset that are differentially regulated. Significantly, genetic analysis of lsk1Δ aip1Δ double mutants is consistent with Lsk1p and Aip1p acting in a linear pathway with respect to the regulation of cytokinesis.

  18. Live-cell Imaging of Pol II Promoter Activity to Monitor Gene expression with RNA IMAGEtag reporters

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ilchung [Ames Laboratory; Ray, Judhajeet [Ames Laboratory; Gupta, Vinayak [Iowa State University; Ilgu, Muslum [Ames Laboratory; Beasley, Jonathan [Iowa State University; Bendickson, Lee [Ames Laboratory; Mehanovic, Samir [Molecular Express; Kraus, George A. [Iowa State University; Nilsen-Hamilton, Marit [Ames Laboratory

    2014-04-20

    We describe a ribonucleic acid (RNA) reporter system for live-cell imaging of gene expression to detect changes in polymerase II activity on individual promoters in individual cells. The reporters use strings of RNA aptamers that constitute IMAGEtags (Intracellular MultiAptamer GEnetic tags) that can be expressed from a promoter of choice. For imaging, the cells are incubated with their ligands that are separately conjugated with one of the FRET pair, Cy3 and Cy5. The IMAGEtags were expressed in yeast from the GAL1, ADH1 or ACT1 promoters. Transcription from all three promoters was imaged in live cells and transcriptional increases from the GAL1 promoter were observed with time after adding galactose. Expression of the IMAGEtags did not affect cell proliferation or endogenous gene expression. Advantages of this method are that no foreign proteins are produced in the cells that could be toxic or otherwise influence the cellular response as they accumulate, the IMAGEtags are short lived and oxygen is not required to generate their signals. The IMAGEtag RNA reporter system provides a means of tracking changes in transcriptional activity in live cells and in real time.

  19. Oxidative Metabolites of Curcumin Poison Human Type II Topoisomerases†

    Science.gov (United States)

    Ketron, Adam C.; Gordon, Odaine N.; Schneider, Claus; Osheroff, Neil

    2013-01-01

    The polyphenol curcumin is the principal flavor and color component of the spice turmeric. Beyond its culinary uses, curcumin is believed to positively impact human health and displays antioxidant, anti-inflammatory, antibacterial, and chemopreventive properties. It also is in clinical trials as an anticancer agent. In aqueous solution at physiological pH, curcumin undergoes spontaneous autoxidation that is enhanced by oxidizing agents. The reaction proceeds through a series of quinone methide and other reactive intermediates to form a final dioxygenated bicyclopentadione product. Several naturally occurring polyphenols that can form quinones have been shown to act as topoisomerase II poisons (i.e., increase levels of topoisomerase II-mediated DNA cleavage). Because several of these compounds have chemopreventive properties, we determined the effects of curcumin, its oxidative metabolites, and structurally related degradation products (vanillin, ferulic acid, and feruloylmethane), on the DNA cleavage activities of human topoisomerase IIα and IIβ. Intermediates in the curcumin oxidation pathway increased DNA scission mediated by both enzymes ~4-5–fold. In contrast, curcumin and the bicyclopentadione, as well as vanillin, ferulic acid, and feruloylmethane, had no effect on DNA cleavage. As found for other quinone-based compounds, curcumin oxidation intermediates acted as redox-dependent (as opposed to interfacial) topoisomerase II poisons. Finally, under conditions that promote oxidation, the dietary spice turmeric enhanced topoisomerase II-mediated DNA cleavage. Thus, even within the more complex spice formulation, oxidized curcumin intermediates appear to function as topoisomerase II poisons. PMID:23253398

  20. RNA-DNA Differences Are Generated in Human Cells within Seconds after RNA Exits Polymerase II

    Directory of Open Access Journals (Sweden)

    Isabel X. Wang

    2014-03-01

    Full Text Available RNA sequences are expected to be identical to their corresponding DNA sequences. Here, we found all 12 types of RNA-DNA sequence differences (RDDs in nascent RNA. Our results show that RDDs begin to occur in RNA chains ∼55 nt from the RNA polymerase II (Pol II active site. These RDDs occur so soon after transcription that they are incompatible with known deaminase-mediated RNA-editing mechanisms. Moreover, the 55 nt delay in appearance indicates that they do not arise during RNA synthesis by Pol II or as a direct consequence of modified base incorporation. Preliminary data suggest that RDD and R-loop formations may be coupled. These findings identify sequence substitution as an early step in cotranscriptional RNA processing.

  1. BcII RFLP for the human vimentin gene

    Energy Technology Data Exchange (ETDEWEB)

    Marcus, E M; Smith, B A; Telenius, H; Ponder, B A.J.; Mathew, C G.P. [Haddow Laboratories, Surrey (England); Landsvater, R M; Buys, C H.C.M. [State Univ. of Groningen (Netherlands); Ferrari, S [Temple University Medical School, Philadelphia, PA (USA)

    1988-09-26

    A 1.1 kb cDNA clone (hp4F1) encoding the human vimentin gene was identified in a human library by screening with 4F1, a hamster vimentin cDNA. BcII (TGATCA) recognizes a two allele polymorphism: bands A1 at 8.1 kb, and A2 at 3.6 kb. The allele frequency was determined in 47 unrelated Caucasian individuals. The RFLP was mapped to chromosome 10pter-10q23 using somatic cell hybrids and to 10p13 by in situ hybridization. Co-dominant segregation was observed in 2 informative families.

  2. Genomic binding profiles of functionally distinct RNA polymerase III transcription complexes in human cells.

    Science.gov (United States)

    Moqtaderi, Zarmik; Wang, Jie; Raha, Debasish; White, Robert J; Snyder, Michael; Weng, Zhiping; Struhl, Kevin

    2010-05-01

    Genome-wide occupancy profiles of five components of the RNA polymerase III (Pol III) machinery in human cells identified the expected tRNA and noncoding RNA targets and revealed many additional Pol III-associated loci, mostly near short interspersed elements (SINEs). Several genes are targets of an alternative transcription factor IIIB (TFIIIB) containing Brf2 instead of Brf1 and have extremely low levels of TFIIIC. Strikingly, expressed Pol III genes, unlike nonexpressed Pol III genes, are situated in regions with a pattern of histone modifications associated with functional Pol II promoters. TFIIIC alone associates with numerous ETC loci, via the B box or a novel motif. ETCs are often near CTCF binding sites, suggesting a potential role in chromosome organization. Our results suggest that human Pol III complexes associate preferentially with regions near functional Pol II promoters and that TFIIIC-mediated recruitment of TFIIIB is regulated in a locus-specific manner.

  3. The type II collagen fragments Helix-II and CTX-II reveal different enzymatic pathways of human cartilage collagen degradation

    DEFF Research Database (Denmark)

    Charni-Ben Tabassi, N; Desmarais, S; Jensen, Anne-Christine Bay

    2008-01-01

    human recombinant cathepsins (Cats) and matrix-metalloproteases (MMPs). Next, we analyzed the spontaneous release of Helix-II and CTX-II from cartilage sections of patients with knee OA who were immediately deep frozen after joint replacement to preserve endogenous enzyme activity until assay. Cartilage....... Cat D was unable to digest intact cartilage. MMPs-1, -3, -7, -9, and -13 efficiently released CTX-II, but only small amount of Helix-II. Neither CTX-II nor Helix-II alone was able to reflect accurately the collagenolytic activity of Cats and MMPs as reflected by the release of hydroxyproline. In OA...

  4. Molecular Architecture of the Human Mediator–RNA Polymerase II–TFIIF Assembly

    Science.gov (United States)

    Bernecky, Carrie; Grob, Patricia; Ebmeier, Christopher C.; Nogales, Eva; Taatjes, Dylan J.

    2011-01-01

    The macromolecular assembly required to initiate transcription of protein-coding genes, known as the Pre-Initiation Complex (PIC), consists of multiple protein complexes and is approximately 3.5 MDa in size. At the heart of this assembly is the Mediator complex, which helps regulate PIC activity and interacts with the RNA polymerase II (pol II) enzyme. The structure of the human Mediator–pol II interface is not well-characterized, whereas attempts to structurally define the Mediator–pol II interaction in yeast have relied on incomplete assemblies of Mediator and/or pol II and have yielded inconsistent interpretations. We have assembled the complete, 1.9 MDa human Mediator–pol II–TFIIF complex from purified components and have characterized its structural organization using cryo-electron microscopy and single-particle reconstruction techniques. The orientation of pol II within this assembly was determined by crystal structure docking and further validated with projection matching experiments, allowing the structural organization of the entire human PIC to be envisioned. Significantly, pol II orientation within the Mediator–pol II–TFIIF assembly can be reconciled with past studies that determined the location of other PIC components relative to pol II itself. Pol II surfaces required for interacting with TFIIB, TFIIE, and promoter DNA (i.e., the pol II cleft) are exposed within the Mediator–pol II–TFIIF structure; RNA exit is unhindered along the RPB4/7 subunits; upstream and downstream DNA is accessible for binding additional factors; and no major structural re-organization is necessary to accommodate the large, multi-subunit TFIIH or TFIID complexes. The data also reveal how pol II binding excludes Mediator–CDK8 subcomplex interactions and provide a structural basis for Mediator-dependent control of PIC assembly and function. Finally, parallel structural analysis of Mediator–pol II complexes lacking TFIIF reveal that TFIIF plays a key role in

  5. Determination of activities of human carbonic anhydrase II inhibitors ...

    African Journals Online (AJOL)

    Purpose: To evaluate the activities of new curcumin analogs as carbonic anhydrase II (CA-II) inhibitor. Methods: Carbonic anhydrase II (CA-II) inhibition was determined by each ligand capability to inhibit the esterase activity of CA-II using 4-NPA as a substrate in 96-well plates. Dimethyl sulfoxide was used to dissolve each ...

  6. Blood-group-Ii-active gangliosides of human erythrocyte membranes

    International Nuclear Information System (INIS)

    Feizi, T.; Childs, R.A.; Hakomori, S.-I.; Powell, M.E.

    1978-01-01

    More than ten new types of gangliosides, in addition to haematoside and sialosylparagloboside, were isolated from human erythrocyte membranes. These were separated by successive chromatographies on DAEA-Sephadex, on porous silica-gel columns and on thin-layer silica gel as acetylated compounds. Highly potent blood-group-Ii and moderate blood-group-H activities were demonstrated in some of the ganglioside fractions. The gangliosides incorporated into chlolesterol/phosphatidylcholine liposomes stoicheiometrically inhibited binding of anti-(blood-group-I and i) antibodies to a radioiodinated blood-group-Ii-active glycoprotein. The fraction with the highest blood-group-I activity, I(g) fraction, behaved like sialosyl-deca- to dodeca-glycosylceramides on t.l.c. Certain blood-group-I and most of the i-determinants were in partially or completely cryptic form and could be unmasked by sialidase treatment. Thus the I and i antigens, which are known to occur on internal structures of blood-group-ABH-active glycoproteins in secretions, also occur in the interior of the carbohydrate chains of erythrocyte gangliosides. (author)

  7. DNA structure in human RNA polymerase II promoters

    DEFF Research Database (Denmark)

    Pedersen, Anders Gorm; Baldi, Pierre; Chauvin, Yves

    1998-01-01

    with a very low level of sequence similarity. The sequences, which include both TATA-containing and TATA-less promoters, are aligned by hidden Markov models. Using three different models of sequence-derived DNA bendability, the aligned promoters display a common structural profile with bendability being low...... protein in a manner reminiscent of DNA in a nucleosome. This notion is further supported by the finding that the periodic bendability is caused mainly by the complementary triplet pairs CAG/CTG and GGC/GCC, which previously have been found to correlate with nucleosome positioning. We present models where......The fact that DNA three-dimensional structure is important for transcriptional regulation begs the question of whether eukaryotic promoters contain general structural features independently of what genes they control. We present an analysis of a large set of human RNA polymerase II promoters...

  8. Dual pathway for angiotensin II formation in human internal mammary arteries

    NARCIS (Netherlands)

    Voors, A. A.; Pinto, Y. M.; Buikema, H.; Urata, H.; Oosterga, M.; Rooks, G.; Grandjean, J. G.; Ganten, D.; van Gilst, W. H.

    1998-01-01

    1. Angiotensin converting enzyme (ACE) is thought to be the main enzyme to convert antiotensin I to the vasoactive angiotensin II. Recently, in the human heart, it was found that the majority of angiotensin II formation was due to another enzyme, identified as human heart chymase. In the human

  9. MHC class II molecules regulate growth in human T cells

    DEFF Research Database (Denmark)

    Nielsen, M; Odum, Niels; Bendtzen, K

    1994-01-01

    MHC-class-II-positive T cells are found in tissues involved in autoimmune disorders. Stimulation of class II molecules by monoclonal antibodies (mAbs) or bacterial superantigens induces protein tyrosine phosphorylation through activation of protein tyrosine kinases in T cells, and class II signals...... lines tested. Only one of three CD4+, CD45RAhigh, ROhigh T cells responded to class II costimulation. There was no correlation between T cell responsiveness to class II and the cytokine production profile of the T cell in question. Thus, T cell lines producing interferon (IFN)-gamma but not IL-4 (TH1...... modulate several T cell responses. Here, we studied further the role of class II molecules in the regulation of T cell growth. Costimulation of class II molecules by immobilized HLA-DR mAb significantly enhanced interleukin (IL)-2-supported T cell growth of the majority of CD4+, CD45RAlow, ROhigh T cell...

  10. La cultura política del ciudadano y la comunicación política en TV en la transición política del plebiscito chileno (octubre 1988. I. Metodología. II. Conclusiones

    Directory of Open Access Journals (Sweden)

    JOSÉ LUIS PIÑUEL RAIGADA

    1990-01-01

    Full Text Available Exposición de la acotación material y formal del objeto al que se destina la investigación realizada, y cuyo campo de observación es la situación histórica brindada con la campaña política del plebiscito chileno del 5 de octubre de 1988. La prefiguración teórica de este objeto es la responsable de la selección y consistencia de los datos que se han recolectado y procesado, y la que ha motivado a escoger como campo de observación la COMUNICACIÓN POLÍTICA televisiva y la CULTURA POLÍTICA del ciudadano en el Chile Plebiscitario. De la investigación se concluye que la Mediación comunicativa del Plebiscito ha implantado en la Transición chilena un proceso de resignificación cuyo sentido radica más en la "afirmación del cambio" que en la "afirmación de opciones contra", curiosamente ligadas estas últimas, por la vía de la comunicación, a la opción política cuya práctica no era de cambio, sino de continuidad.

  11. Fragment Screening of Human Kynurenine Aminotransferase-II.

    Science.gov (United States)

    Jayawickrama, Gayan S; Nematollahi, Alireza; Sun, Guanchen; Church, W Bret

    2018-03-01

    Kynurenine aminotransferase-II (KAT-II) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that acts in the tryptophan metabolic pathway by catalyzing the transamination of kynurenine into kynurenic acid (KYNA). It is one of four isoforms in the KAT family, of which it is the primary homologue responsible for KYNA production in the mammalian brain. KAT-II is targeted for inhibition as KYNA is implicated in diseases such as schizophrenia, where it is found in elevated concentrations. Previously, many different approaches have been taken to develop KAT-II inhibitors, and herein fragment-based drug design (FBDD) approaches have been exploited to provide further lead compounds that can be designed into novel inhibitors. Surface plasmon resonance (SPR) was used to screen a fragment library containing 1000 compounds, of which 41 hits were identified. These hits were further evaluated with SPR, and 18 were selected for inhibition studies. From these hits, two fragments, F6037-0164 and F0037-7280, were pursued and determined to have an IC 50 of 524.5 (± 25.6) μM and 115.2 (± 4.5) μM, respectively. This strategy shows the viability of using FBDD in gleaning knowledge about KAT-II inhibition and generating leads for the production of KAT-II inhibitors.

  12. Dual pathway for angiotensin II formation in human internal mammary arteries

    NARCIS (Netherlands)

    Voors, AA; Pinto, YM; Buikema, H; Urata, H; Oosterga, M; Roos, G; Grandjean, JG; Ganten, D; van Gilst, WH

    1 Angiotensin converting enzyme (ACE) is thought to be the main enzyme to convect antiotensin I to the vasoactive angiotensin II. Recently, in the human heart, it was found that the majority of angiotensin ZI formation was due to another enzyme, identified as human heart chymase. In the human

  13. Regulated gene expression in cultured type II cells of adult human lung

    OpenAIRE

    Ballard, Philip L.; Lee, Jae W.; Fang, Xiaohui; Chapin, Cheryl; Allen, Lennell; Segal, Mark R.; Fischer, Horst; Illek, Beate; Gonzales, Linda W.; Kolla, Venkatadri; Matthay, Michael A.

    2010-01-01

    Alveolar type II cells have multiple functions, including surfactant production and fluid clearance, which are critical for lung function. Differentiation of type II cells occurs in cultured fetal lung epithelial cells treated with dexamethasone plus cAMP and isobutylmethylxanthine (DCI) and involves increased expression of 388 genes. In this study, type II cells of human adult lung were isolated at ∼95% purity, and gene expression was determined (Affymetrix) before and after culturing 5 days...

  14. Cloning and expression of a novel human profilin variant, profilin II

    DEFF Research Database (Denmark)

    Honoré, B; Madsen, Peder; Andersen, A H

    1993-01-01

    We have isolated a 1.7 kbp cDNA encoding a 140 amino acid protein (15.1 kDa, pI 5.91) with a high sequence similarity (62%) to human profilin (profilin I). We have termed this variant profilin II. Northern blot analysis showed that profilin II is highly expressed in brain, skeletal muscle and kid...

  15. Expression of the pol gene of human endogenous retroviruses HERV-K and -W in leukemia patients.

    Science.gov (United States)

    Bergallo, Massimiliano; Montanari, Paola; Mareschi, Katia; Merlino, Chiara; Berger, Massimo; Bini, Ilaria; Daprà, Valentina; Galliano, Ilaria; Fagioli, Franca

    2017-12-01

    The human endogenous retroviruses (HERVs) are a family of endogenous retroviruses that integrated into the germ cell DNA of primates over 30 million years ago. HERV expression seems impaired in several diseases, ranging from autoimmune to neoplastic disorders. The purpose of this study was to evaluate the overall endogenous retroviral transcription profile in bone marrow (BM) samples. A total of 30 paediatric high-risk leukaemia patients (lymphoid and myeloid malignancies) were tested for HERVs virus gene expression. Our findings show that HERV-K expression was significantly higher in leukaemia patients when compared to healthy donors of a similar median age. We observed a significantly high expression of HERV-K in acute lymphoblastic leukemia (ALL) patients. In this study, we also found a relative overexpression of the endogenous retrovirus HERV-K in BM cells from the majority of leukemia samples analyzed, in particular in ALL. This overexpression might be related to lymphatic leukemogenesis and it warrants further investigations.

  16. Direitos humanos: o significado político da conferência de Viena The Viena conference on human rights

    Directory of Open Access Journals (Sweden)

    José Augusto Lindgren Alves

    1994-04-01

    Full Text Available Do momento em que a idéia de chamar uma nova Conferencia Mundial Sobre Direitos Humanos foi inicialmente discutida pela Assembléia Geral da ONU, em 1989, até seu término, em 1993 em Viena, a situação internacional evoluiu de forma negativa. O agravamento de conflitos no período afetou o processo de preparação e os debates que ocorreram em Viena a um tal ponto, que chegou-se a temer por um fracasso total da Conferência. Em vista dessas circunstâncias, a Declaração e o Programa de Ação finais, adotados por consenso, apresentam-se como realizações positivas, propondo conceitos e recomendações que tendem a contribuir para a causa dos direitos humanos.Since the idea of convening a new World Conference on Human Rights was first discussed in 1989 by the U.N. General Assembly till its effective conclusion in Vienna four years later, the international situation became worse. The aggravation of crises and conflicts in the period affected both the preparatory process and the discussions held in Vienna to such an extent that fears arose regarding the possible failure of the Conference. In view of those circumstances, the final Declaration and Program of Action, adopted by consensus, stand as a positive achievement, with concepts and recommendations that tend to contribute to the cause of human rights.

  17. Determination of activities of human carbonic anhydrase II inhibitors ...

    African Journals Online (AJOL)

    the esterase activity of CA-II using 4-NPA as a substrate in 96-well plates. Dimethyl sulfoxide was used ... intensive search for novel drugs is ongoing, through synthesis of new ..... License (http://creativecommons.org/licenses/by/. 4.0) and the ...

  18. Gramsci between Machiavelli and Marx: from negative determination of human to ontonegative determination of politics Gramsci entre Maquiavel e Marx: da negatividade do homem a ontonegatividade da política

    Directory of Open Access Journals (Sweden)

    Claudinei Cássio Rezende

    2008-12-01

    Full Text Available In one of his central categories, Gramsci establishes a connection between the Machiavellian and Marxian political conceptions, in a manner that each one writes to the revolutionary class of their time. Nevertheless, a more rigorous critic at Marx’s propositions unveils to us that the proletarian class isn’t just the progressist class of his time, in the same manner that the bourgeois was in the Iluminism, like Gramsci thinks, but it is, actually, the universal sphere and the only one qualifi ed to accomplish a human emancipation. Consequently, the connection between Machiavelli and Marx does not exist, once Marx conceives the ontological work as the central attribute of humanization, and conceives the politics as temporary; while Machiavelli conceives the politics as the founder act of all sociability. Keywords: Machiavelli. Marx. Gramsci. Ontonegative determination of politics. Human emancipation. Em uma de suas categorias centrais, Gramsci estabelece uma identidade direta entre as politicidades maquiaveliana e marxiana, de sorte que cada um escreve para a classe da vanguarda política de sua época. No entanto, uma crítica mais rigorosa aos escritos marxianos nos revela que o proletariado não é somente a classe progressista de sua época, da maneira que a burguesia fora no iluminismo, como quer Gramsci, mas é, em verdade, a esfera universal e a única capaz de levar a cabo uma emancipação humana total. Doravante, a identidade entre Marx e Maquiavel inexiste na medida em que o primeiro, de magnitude filosófica distinta, concebe o trabalho ontologicamente como atributo central da humanização, apreendendo a política como uma figura transitória superável, enquanto o segundo concebe a política como o ato fundador de toda sociabilidade. Palavras-chave: Maquiavel. Marx. Gramsci. Ontonegatividade da política. Emancipação humana.

  19. Identification and characterization of the human type II collagen gene (COL2A1).

    OpenAIRE

    Cheah, Kathryn; Stoker, N.G.; Griffin, J.R.; Grosveld, Frank; Solomon, E.

    1985-01-01

    textabstractThe gene contained in the human cosmid clone CosHcol1, previously designated an alpha 1(I) collagen-like gene, has now been identified. CosHcol1 hybridizes strongly to a single 5.9-kilobase mRNA species present only in tissue in which type II collagen is expressed. DNA sequence analysis shows that this clone is highly homologous to the chicken alpha 1(II) collagen gene. These data together suggest that CosHcol1 contains the human alpha 1(II) collagen gene COL2A1. The clone appears...

  20. Eclalbasaponin II induces autophagic and apoptotic cell death in human ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Yoon Jin Cho

    2016-09-01

    Full Text Available Triterpenoids echinocystic acid and its glycosides, isolated from several Eclipta prostrata, have been reported to possess various biological activities such as anti-inflammatory, anti-bacterial, and anti-diabetic activity. However, the cytotoxicity of the triterpenoids in human cancer cells and their molecular mechanism of action are poorly understood. In the present study, we found that eclalbasaponin II with one glucose moiety has potent cytotoxicity in three ovarian cancer cells and two endometrial cancer cells compared to an aglycone echinocystic acid and eclalbasaponin I with two glucose moiety. Eclalbasaponin II treatment dose-dependently increased sub G1 population. Annexin V staining revealed that eclalbasaponin II induced apoptosis in SKOV3 and A2780 ovarian cancer cells. In addition, eclalbasaponin II-induced cell death was associated with characteristics of autophagy; an increase in acidic vesicular organelle content and elevation of the levels of LC3-II. Interestingly, autophagy inhibitor BaF1 suppressed the eclalbasaponin II-induced apoptosis. Moreover, eclalbasaponin II activated JNK and p38 signaling and inhibited the mTOR signaling. We further demonstrated that pre-treatment with a JNK and p38 inhibitor and mTOR activator attenuated the eclalbasaponin II-induced autophagy. This suggests that eclalbasaponin II induces apoptotic and autophagic cell death through the regulation of JNK, p38, and mTOR signaling in human ovarian cancer cells.

  1. Detection and quantitation of glutamate carboxypeptidase II in human blood

    Czech Academy of Sciences Publication Activity Database

    Knedlík, Tomáš; Navrátil, Václav; Vik, V.; Pacík, D.; Šácha, Pavel; Konvalinka, Jan

    2014-01-01

    Roč. 74, č. 7 (2014), s. 768-780 ISSN 0270-4137 R&D Projects: GA ČR GAP304/12/0847 Grant - others:OPPC(CZ) CZ.2.16/3.1.00/24016 Institutional support: RVO:61388963 Keywords : serum marker * glutamate carboxypeptidase II * plasma glutamate carboxypeptidase * prostate cancer * prostate -specific membrane antigen Subject RIV: CE - Biochemistry Impact factor: 3.565, year: 2014

  2. Noncooperative cadmium(II) binding to human metallothionein 1a

    International Nuclear Information System (INIS)

    Sutherland, Duncan E.K.; Stillman, Martin J.

    2008-01-01

    The two-domain (βα) mammalian metallothionein binds seven divalent metals, however, the binding mechanism is not well characterized and recent reports require the presence of the partially metallated protein. In this paper, step-wise metallation of the metal-free, two-domain βα-rhMT and the isolated β-rhMT using Cd(II) is shown to proceed in a noncooperative manner by analysis of electrospray ionization mass spectrometric data. Under limiting amounts of Cd(II), all intermediate metallation states up to the fully metallated Cd 3 -β-rhMT and Cd 7 -βα-rhMT were observed. Addition of excess Cd(II), resulted in formation of the supermetallated (metallation in excess of normal levels) Cd 4 -β- and Cd 8 -βα-metallothionein species. These data establish that noncooperative cadmium metallation is a property of each isolated domain and the complete two-domain protein. Our data now also establish that supermetallation is a property that may provide information about the mechanism of metal transfer to other proteins

  3. A review on architecture of the gag-pol ribosomal frameshifting RNA in human immunodeficiency virus: a variability survey of virus genotypes.

    Science.gov (United States)

    Qiao, Qi; Yan, Yanhua; Guo, Jinmei; Du, Shuqiang; Zhang, Jiangtao; Jia, Ruyue; Ren, Haimin; Qiao, Yuanbiao; Li, Qingshan

    2017-06-01

    Programmed '-1' ribosomal frameshifting is necessary for expressing the pol gene overlapped from a gag of human immunodeficiency virus. A viral RNA structure that requires base pairing across the overlapping sequence region suggests a mechanism of regulating ribosome and helicase traffic during expression. To get precise roles of an element around the frameshift site, a review on architecture of the frameshifting RNA is performed in combination of reported information with augments of a representative set of 19 viral samples. In spite of a different length for the viral RNAs, a canonical comparison on the element sequence allocation is performed for viewing variability associations between virus genotypes. Additionally, recent and historical insights recognized in frameshifting regulation are looked back as for indel and single nucleotide polymorphism of RNA. As specially noted, structural changes at a frameshift site, the spacer sequence, and a three-helix junction element, as well as two Watson-Crick base pairs near a bulge and a C-G pair close a loop, are the most vital strategies for the virus frameshifting regulations. All of structural changes, which are dependent upon specific sequence variations, facilitate an elucidation about the RNA element conformation-dependent mechanism for frameshifting. These facts on disrupting base pair interactions also allow solving the problem of competition between ribosome and helicase on a same RNA template, common to single-stranded RNA viruses. In a broad perspective, each new insight of frameshifting regulation in the competition systems introduced by the RNA element construct changes will offer a compelling target for antiviral therapy.

  4. Principais políticas de fomento do turismo na Amazônia: análise dos primeiros planos de turismo da Amazônia (PTA I e II e do PROECOTUR

    Directory of Open Access Journals (Sweden)

    Kassia Suelen da Silva Farias

    2015-01-01

    Full Text Available Verifica-se que o turismo tem passado por inúmeras transformações no que concerne ao planejamento e gestão da atividade. Observa-se que desde a década de 1970 tem-se pensado em diferentes modelos de desenvolvimento de turismo para a Amazônia, almejando o progresso econômico e social. Neste processo, na década de 1970, a Superintendência de Desenvolvimento da Amazônia (SUDAM, deu inicio a discursão de criação do primeiro Plano de Turismo da Amazônia (PTA que deu inicio na década de 1980 até 1985. A partir da década de 1990 as estratégias de turismo para a região foram desenvolvidas em conformidade com a preocupação mundial em torno da natureza e do homem. Produto deste contexto, o II PTA foi lançado com o objetivo principal de desenvolver medidas que conciliassem o desenvolvimento econômico às questões ambientais e sociais. Outra ação também importante para esse período foi a promoção do desenvolvimento regional por meio de polos de turismo integrados, conforme determinava o PROECOTUR. O objetivo deste artigo, portanto, consiste em destacar as primeiras políticas públicas de turismo para o desenvolvimento dos estados e municípios da Amazônia que deram inicio a partir de 1970. Para isso, a estruturação conceitual do trabalho fundamentou-se em políticas públicas e planejamento de turismo na Amazônia. Utiliza-se como metodologia a pesquisa documental, por meio de diagnóstico que enfatiza os principais resultados obtidos pelos I e II Planos de Turismo da Amazônia, a partir da interpretação e análise documental; O artigo também adota a pesquisa bibliográfica, pois analisa as principais estratégias de desenvolvimento do turismo na Amazônia. A partir de tal análise, conclui-se que as mudanças políticas de turismo ocorridas na Amazônia entre a década de 1970 e 1990 - apesar de estarem acompanhadas por ações de planejamento do governo nacional e até mesmo pelas tendências mundiais - n

  5. Síntese, caracterização e estudo das propriedades magnéticas de um polímero de coordenação contendo cobalto(II e cobre(II

    Directory of Open Access Journals (Sweden)

    Tamyris T. da Cunha

    2012-01-01

    Full Text Available This work describes the synthesis and characterization of two new compounds with ligand opy (N-(2-pyridyloxamate: the copper(II precursor [Me4N]2[Cu(opy2].5H2O and CoII CuII coordination polymer {[CoCu(opy2]}n×4nH2O. This latter compound was obtained by reaction of [Me4N]2[Cu(opy2].5H2O and CoCl2.6H2O in water. The heterobimetallic CoII CuII chain was characterized by elemental analysis, IR spectroscopy, thermogravimetry and magnetic measurements. Magnetic characterization revealed typical behavior of one-dimensional (1D ferrimagnetic chain as shown in the curves of temperature (T dependence of magnetic susceptibility (χM, in the form of χMT versus T, and dependence of magnetization (M with applied field (H.

  6. Insulin-like growth factor II (IGF II) in human brain: regional distribution of IGF II and of higher molecular mass forms

    International Nuclear Information System (INIS)

    Haselbacher, G.K.; Schwab, M.E.; Pasi, A.; Humbel, R.E.

    1985-01-01

    Twenty-four distinct areas of human brain were analyzed for the presence of insulin-like growth factor (IGF). As reported for cerebrospinal fluid, only IGF II-like immunoreactivity, but no significant amounts of IGF I-like immunoreactivity, could be found. Upon gel permeation chromatography, two to five distinct size classes were separated on the basis of their immunoreactivity. Radioimmunoassays and a bioassay also gave results indistinguishable from those of serum IGF II. The highest amounts of IGF II-like immunoreactivity occur in the anterior pituitary. This is up to 100 times more than in most other brain regions analyzed. The higher molecular mass immunoreactive species were partially characterized. After immunoaffinity purification, the 38- and 26-kDa species are active in a bioassay. Specific IGF-binding protein activity could be shown after purification of the 38- and 26-kDa species on an IGF-affinity column. The 13-kDa species released significant amounts of 7.5-kDa material. The results are interpreted as evidence for the presence of IGF II synthesized locally in human brain

  7. Investigation of the proteins relaxation time in human blood serum; Badania relaksacyjne bialek surowicy krwi II

    Energy Technology Data Exchange (ETDEWEB)

    Blicharska, B.; Klauza, M. [Inst. Fizyki, Uniwersytet Jagiellonski, Cracow (Poland); Kuliszkiewicz-Janus, M. [Akademia Medyczna, Wroclaw (Poland)

    1994-12-31

    In this paper the results of human blood serum proteins relaxation time measurements by means of NMR method are presented. The measurements have been done for three samples of human blood: i/laudably ii/leukemia iii/granulomas. The dependences of the relaxation time on the temperature are also presented. 3 refs, 4 figs.

  8. Development of human factors design review guidelines(II)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea)

    1998-06-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: 25. Human Factors Engineering Program Review Model and 26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation, which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents of NUREG-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994. (author). 11 refs., 2 figs., 2 tabs.

  9. Development of human factors design review guidelines(II)

    International Nuclear Information System (INIS)

    Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul

    1998-06-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25, human factors engineering program review model' and '26, review criteria for human factors aspects of advanced controls and instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents NUREG--0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm system. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994

  10. Example of human individual identification from World War II gravesite.

    Science.gov (United States)

    Ossowski, Andrzej; Kuś, Marta; Brzeziński, Piotr; Prüffer, Jakub; Piątek, Jarosław; Zielińska, Grażyna; Bykowska, Milena; Jałowińska, Katarzyna; Torgaszev, Anton; Skoryukov, Antoliy; Parafiniuk, Mirosław

    2013-12-10

    This paper presents the procedure elaborated by our team which was applied to the mode of identification of Red Army soldiers who were taken as prisoners by the German Army during World War II and deceased in captivity. In the course of our search the unmarked burial of ten Soviet prisoners of war was found. Historical, anthropological and genetic research conducted by us led to the personal identification of nine of them, including two by means of DNA analysis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Política tarifária no II Reinado: evolução e impactos, 1850-1889

    Directory of Open Access Journals (Sweden)

    André Villela

    2009-06-01

    Full Text Available The article analyses the evolution of Brazilian tariff policy between 1844 and 1889. At first a review of the various tariff schedules adopted during the period is made, with their main features highlighted. The next section seeks to assess the impact of tariff policy on the degree of protection afforded to the domestic sector. To that effect, three types of exercises are carried out: first, the “real cost of imports” and its determinants are calculated; we then calculate coefficients of partial correlation between the quantity of imports, GDP, price of imports, the rate of exchange and import tariffs; finally, we estimate econometrically import demand equations. The exercises reveal that during the II Reign tariffs were important in explaining variations in total imports, although this importance diminished after 1869.

  12. Inference of RNA polymerase II transcription dynamics from chromatin immunoprecipitation time course data.

    Directory of Open Access Journals (Sweden)

    Ciira wa Maina

    2014-05-01

    Full Text Available Gene transcription mediated by RNA polymerase II (pol-II is a key step in gene expression. The dynamics of pol-II moving along the transcribed region influence the rate and timing of gene expression. In this work, we present a probabilistic model of transcription dynamics which is fitted to pol-II occupancy time course data measured using ChIP-Seq. The model can be used to estimate transcription speed and to infer the temporal pol-II activity profile at the gene promoter. Model parameters are estimated using either maximum likelihood estimation or via Bayesian inference using Markov chain Monte Carlo sampling. The Bayesian approach provides confidence intervals for parameter estimates and allows the use of priors that capture domain knowledge, e.g. the expected range of transcription speeds, based on previous experiments. The model describes the movement of pol-II down the gene body and can be used to identify the time of induction for transcriptionally engaged genes. By clustering the inferred promoter activity time profiles, we are able to determine which genes respond quickly to stimuli and group genes that share activity profiles and may therefore be co-regulated. We apply our methodology to biological data obtained using ChIP-seq to measure pol-II occupancy genome-wide when MCF-7 human breast cancer cells are treated with estradiol (E2. The transcription speeds we obtain agree with those obtained previously for smaller numbers of genes with the advantage that our approach can be applied genome-wide. We validate the biological significance of the pol-II promoter activity clusters by investigating cluster-specific transcription factor binding patterns and determining canonical pathway enrichment. We find that rapidly induced genes are enriched for both estrogen receptor alpha (ERα and FOXA1 binding in their proximal promoter regions.

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  14. Radioimmunodetection of human pancreatic tumor xenografts using DU-PAN II monoclonal antibody

    International Nuclear Information System (INIS)

    Nakamura, Kayoko; Kubo, Atsushi; Hashimoto, Shozo; Furuuchi, Takayuki; Abe, Osahiko; Takami, Hiroshi.

    1988-01-01

    The potential of DU-PAN II, monoclonal antibody (IgM), which was raised against the human tumor cell line, was evaluated for radioimmunodetection of human pancreatic tumors (PAN-5-JCK and EXP-58) grown in nude mice. 125 I-labeled DU-PAN II was accumulated into PAN-5-JCK producing DU-PAN II antigen with a tumor-to-blood ratio of 2.72 ± 3.00, but it did not localize in EXP-58 because of insufficient DU-PAN II. There was no significant uptake of 125 I-nonimmunized IgM in PAN-5-JCK. These facts indicated the specific tumor uptake of DU-PAN II. Excellent images of the tumor PAN-5-JCK were obtained 3 days after the injection of 125 I-DU-PAN II. Gel chromatography was also investigated with respect to the plasma taken from mice injected with antibody, or incubated with antibody in vitro. The results indicate that circulating antigen affected the tumor uptake of DU-PAN II: The more the tumor grew, the higher the amount of antigen excreted into the blood, leading to the degradation of DU-PAN II before it reached the tumor sites. Consequently, the immunoscintigram of the small tumor was remarkably clear. The catabolism and the radiolysis of the labeled IgM injected are critical points in applying immunoscintigraphy. (author)

  15. [Bartonellosis. II. Other Bartonella responsible for human diseases].

    Science.gov (United States)

    Piémont, Y; Heller, R

    1999-01-01

    In addition to Bartonella henselae, five other Bartonella species were involved in human pathology. As for B. henselae, ectoparasites seem to be responsible for the transmission of most or all these bacterial species. B. bacilliformis is responsible for Carrion's disease that occurs in some valleys of Colombia, Ecuador and Peru. This disease is transmitted by biting of infected sandflies. The bacterial reservoir is constituted by humans only. That disease occurs either as an acute form with severe infectious hemolytic anemia (or Oroya fever), or as benign cutaneous tumors, also called verruga peruana. Healthy blood carriers of the bacterium exist. Trench fever was described during the First World War. This non-lethal disease is constituted of recurrent febrile attacks associated particularly with osseous pains. The causative agent of the disease is B. quintana, transmitted by the body louse. Humans seem to be the reservoir of that bacterium. In some patients, B. quintana can be responsible for endocarditis, bacillary angiomatosis and chronic or recurrent bacteremia. Other human infections due to Bartonella sp. have been described: B. vinsonii, isolated from blood of small rodents, and B. elizabethae, the reservoir of which is currently unknown, can be responsible for endocardites. B. clarridgeiae (isolated from blood of 5% of pet cats and 17% of stray cats) may be responsible for human cat scratch disease. All these bartonelloses are diagnosed by non-standard blood culture or by in vitro DNA amplification or by serological testing. Their treatment requires tetracyclines or chloramphenicol or macrolides.

  16. Cholinergic neurotransmission in human corpus cavernosum. II. Acetylcholine synthesis

    International Nuclear Information System (INIS)

    Blanco, R.; De Tejada, S.; Goldstein, I.; Krane, R.J.; Wotiz, H.H.; Cohen, R.A.

    1988-01-01

    Physiological and histochemical evidence indicates that cholinergic nerves may participate in mediating penile erection. Acetylcholine synthesis and release was studied in isolated human corporal tissue. Human corpus cavernosum incubated with [ 3 H]choline accumulated [ 3 H]choline and synthesized [ 3 H]acethylcholine in an concentration-dependent manner. [ 3 H]Acetylcholine accumulation by the tissue was inhibited by hemicholinium-3, a specific antagonist of the high-affinity choline transport in cholinergic nerves. Transmural electrical field stimulation caused release of [ 3 H]acetylcholine which was significantly diminished by inhibiting neurotransmission with calcium-free physiological salt solution or tetrodotoxin. These observations provide biochemical and physiological evidence for the existence of cholinergic innervation in human corpus cavernosum

  17. Introduction: Radical Teaching About Human Rights Part II

    Directory of Open Access Journals (Sweden)

    Michael Bennett

    2016-02-01

    Full Text Available In our introduction to the first of these two issues of Radical Teacher devoted to “Radical Teaching About Human Rights,” we cautioned that all forms of Human Rights Education (HRE are not radical.  The problem, we pointed out, with rights discourse is that it can mask the politics of how rights are defined, whose rights are recognized, and how they are enforced.  This problem becomes evident when HRE is bound up with a neoliberal, or worse than neoliberal, perspective that points fingers at others and rallies troops for supposedly humanitarian interventions while eliding the role of the United States as an imperializing settler colonial state.  Fortunately, we have once again received several essays that seem to us to be aware of this danger and provide admirable examples of radical teaching about human rights.

  18. Dilemas da cooperação: conflitos gerados pela política das "Listas Negras" no Brasil durante a Segunda Guerra Mundial Dilemmas of cooperation: the conflicts provoked by the policy of "Black Lists" in Brazil during World War II

    Directory of Open Access Journals (Sweden)

    Tania Quintaneiro

    2006-12-01

    Full Text Available No artigo são analisados os conflitos políticos gerados pela implementação das "Listas Negras" norte-americanas entre órgãos estatais e interesses privados no Brasil durante a Segunda Guerra Mundial.The article analyses the political conflicts caused by the implementation of American Black Lists between State agencies and private interests in Brazil during World War II.

  19. A compromised yeast RNA polymerase II enhances UV sensitivity in the absence of global genome nucleotide excision repair.

    Science.gov (United States)

    Wong, J M; Ingles, C J

    2001-02-01

    Nucleotide excision repair is the major pathway responsible for removing UV-induced DNA damage, and is therefore essential for cell survival following exposure to UV radiation. In this report, we have assessed the contributions of some components of the RNA polymerase II (Pol II) transcription machinery to UV resistance in Saccharomyces cerevisiae. Deletion of the gene encoding the Pol II elongation factor TFIIS (SII) resulted in enhanced UV sensitivity, but only in the absence of global genome repair dependent on the RAD7 and RAD16 genes, a result seen previously with deletions of RAD26 and RAD28, yeast homologs of the human Cockayne syndrome genes CSB and CSA, respectively. A RAD7/16-dependent reduction in survival after UV irradiation was also seen in the presence of mutations in RNA Pol II that confer a defect in its response to SII, as well as with other mutations which reside in regions of the largest subunit of Pol II not involved in SII interactions. Indeed, an increase in UV sensitivity was achieved by simply decreasing the steadystate level of RNA Pol II. Truncation of the C-terminal domain and other RNA Pol II mutations conferred sensitivity to the ribonucleotide reductase inhibitor hydroxyurea and induction of RNR1 and RNR2 mRNAs after UV irradiation was attenuated in these mutant cells. That UV sensitivity can be a consequence of mutations in the RNA Pol II machinery in yeast cells suggests that alterations in transcriptional programs could underlie some of the pathophysiological defects seen in the human disease Cockayne syndrome.

  20. An H3K9/S10 methyl-phospho switch modulates Polycomb and Pol II binding at repressed genes during differentiation.

    Science.gov (United States)

    Sabbattini, Pierangela; Sjoberg, Marcela; Nikic, Svetlana; Frangini, Alberto; Holmqvist, Per-Henrik; Kunowska, Natalia; Carroll, Tom; Brookes, Emily; Arthur, Simon J; Pombo, Ana; Dillon, Niall

    2014-03-01

    Methylated histones H3K9 and H3K27 are canonical epigenetic silencing modifications in metazoan organisms, but the relationship between the two modifications has not been well characterized. H3K9me3 coexists with H3K27me3 in pluripotent and differentiated cells. However, we find that the functioning of H3K9me3 is altered by H3S10 phosphorylation in differentiated postmitotic osteoblasts and cycling B cells. Deposition of H3K9me3/S10ph at silent genes is partially mediated by the mitogen- and stress-activated kinases (MSK1/2) and the Aurora B kinase. Acquisition of H3K9me3/S10ph during differentiation correlates with loss of paused S5 phosphorylated RNA polymerase II, which is present on Polycomb-regulated genes in embryonic stem cells. Reduction of the levels of H3K9me3/S10ph by kinase inhibition results in increased binding of RNAPIIS5ph and the H3K27 methyltransferase Ezh1 at silent promoters. Our results provide evidence of a novel developmentally regulated methyl-phospho switch that modulates Polycomb regulation in differentiated cells and stabilizes repressed states.

  1. Processing sites in the human immunodeficiency virus type 1 (HIV-1 Gag-Pro-Pol precursor are cleaved by the viral protease at different rates

    Directory of Open Access Journals (Sweden)

    Lindquist Jeffrey N

    2005-11-01

    Full Text Available Abstract We have examined the kinetics of processing of the HIV-1 Gag-Pro-Pol precursor in an in vitro assay with mature protease added in trans. The processing sites were cleaved at different rates to produce distinct intermediates. The initial cleavage occurred at the p2/NC site. Intermediate cleavages occurred at similar rates at the MA/CA and RT/IN sites, and to a lesser extent at sites upstream of RT. Late cleavages occurred at the sites flanking the protease (PR domain, suggesting sequestering of these sites. We observed paired intermediates indicative of half- cleavage of RT/RH site, suggesting that the RT domain in Gag-Pro-Pol was in a dimeric form under these assay conditions. These results clarify our understanding of the processing kinetics of the Gag-Pro-Pol precursor and suggest regulated cleavage. Our results further suggest that early dimerization of the PR and RT domains may serve as a regulatory element to influence the kinetics of processing within the Pol domain.

  2. Processing sites in the human immunodeficiency virus type 1 (HIV-1) Gag-Pro-Pol precursor are cleaved by the viral protease at different rates.

    Science.gov (United States)

    Pettit, Steve C; Lindquist, Jeffrey N; Kaplan, Andrew H; Swanstrom, Ronald

    2005-11-01

    We have examined the kinetics of processing of the HIV-1 Gag-Pro-Pol precursor in an in vitro assay with mature protease added in trans. The processing sites were cleaved at different rates to produce distinct intermediates. The initial cleavage occurred at the p2/NC site. Intermediate cleavages occurred at similar rates at the MA/CA and RT/IN sites, and to a lesser extent at sites upstream of RT. Late cleavages occurred at the sites flanking the protease (PR) domain, suggesting sequestering of these sites. We observed paired intermediates indicative of half- cleavage of RT/RH site, suggesting that the RT domain in Gag-Pro-Pol was in a dimeric form under these assay conditions. These results clarify our understanding of the processing kinetics of the Gag-Pro-Pol precursor and suggest regulated cleavage. Our results further suggest that early dimerization of the PR and RT domains may serve as a regulatory element to influence the kinetics of processing within the Pol domain.

  3. Human urotensin-II is an endothelium-dependent vasodilator in rat small arteries

    Science.gov (United States)

    Bottrill, Fiona E; Douglas, Stephen A; Hiley, C Robin; White, Richard

    2000-01-01

    The possible role of the endothelium in modulating responses to human urotensin-II (U-II) was investigated using isolated segments of rat thoracic aorta, small mesenteric artery, left anterior descending coronary artery and basilar artery.Human U-II was a potent vasoconstrictor of endothelium-intact isolated rat thoracic aorta (EC50=3.5±1.1 nM, Rmax=103±10% of control contraction induced by 60 mM KCl and 1 μM noradrenaline). However the contractile response was not significantly altered by removal of the endothelium or inhibition of nitric oxide synthesis with L-NAME (100 μM). Human U-II did not cause relaxation of noradrenaline-precontracted, endothelium-intact rat aortae.Human U-II contracted endothelium-intact rat isolated left anterior descending coronary arteries (EC50=1.3±0.8 nM, Rmax=20.1±4.9% of control contraction induced by 10 μM 5-HT). The contractile response was significantly enhanced by removal of the endothelium (Rmax=55.4±16.1%). Moreover, human U-II caused concentration-dependent relaxation of 5-HT-precontracted arteries, which was abolished by L-NAME or removal of the endothelium.No contractile effects of human U-II were found in rat small mesenteric arteries. However the peptide caused potent, concentration- and endothelium-dependent relaxations of methoxamine-precontracted vessels. The relaxant responses were potentiated by L-NAME (300 μM) but abolished in the additional presence of 25 mM KCl (which inhibits the actions of endothelium-derived hyperpolarizing factor).The present study is the first to show that human U-II is a potent endothelium-dependent vasodilator in some rat resistance vessels, and acts through release of EDHF as well as nitric oxide. Our findings have also highlighted clear anatomical differences in the responses of different vascular beds to human U-II which are likely to be important in determining the overall cardiovascular activity of this peptide. PMID:10952676

  4. The TFIID components human TAF(II)140 and Drosophila BIP2 (TAF(II)155) are novel metazoan homologues of yeast TAF(II)47 containing a histone fold and a PHD finger.

    Science.gov (United States)

    Gangloff, Y G; Pointud, J C; Thuault, S; Carré, L; Romier, C; Muratoglu, S; Brand, M; Tora, L; Couderc, J L; Davidson, I

    2001-08-01

    The RNA polymerase II transcription factor TFIID comprises the TATA binding protein (TBP) and a set of TBP-associated factors (TAF(II)s). TFIID has been extensively characterized for yeast, Drosophila, and humans, demonstrating a high degree of conservation of both the amino acid sequences of the constituent TAF(II)s and overall molecular organization. In recent years, it has been assumed that all the metazoan TAF(II)s have been identified, yet no metazoan homologues of yeast TAF(II)47 (yTAF(II)47) and yTAF(II)65 are known. Both of these yTAF(II)s contain a histone fold domain (HFD) which selectively heterodimerizes with that of yTAF(II)25. We have cloned a novel mouse protein, TAF(II)140, containing an HFD and a plant homeodomain (PHD) finger, which we demonstrated by immunoprecipitation to be a mammalian TFIID component. TAF(II)140 shows extensive sequence similarity to Drosophila BIP2 (dBIP2) (dTAF(II)155), which we also show to be a component of Drosophila TFIID. These proteins are metazoan homologues of yTAF(II)47 as their HFDs selectively heterodimerize with dTAF(II)24 and human TAF(II)30, metazoan homologues of yTAF(II)25. We further show that yTAF(II)65 shares two domains with the Drosophila Prodos protein, a recently described potential dTAF(II). These conserved domains are critical for yTAF(II)65 function in vivo. Our results therefore identify metazoan homologues of yTAF(II)47 and yTAF(II)65.

  5. Characterization and immunological identification of cDNA clones encoding two human DNA topoisomerase II isozymes

    International Nuclear Information System (INIS)

    Chung, T.D.Y.; Drake, F.H.; Tan, K.B.; Per, S.R.; Crooke, S.T.; Mirabelli, C.K.

    1989-01-01

    Several DNA topoisomerase II partial cDNA clones obtained from a human Raji-HN2 cDNA library were sequenced and two classes of nucleotide sequences were found. One member of the first class, SP1, was identical to an internal fragment of human HeLa cell Topo II cDNA described earlier. A member of the second class, SP11, shared extensive nucleotide (75%) and predicted peptide (92%) sequence similarities with the first two-thirds of HeLa Topo II. Each class of cDNAs hybridized to unique, nonoverlapping restriction enzyme fragments of genomic DNA from several human cell lines. Synthetic 24-mer oligonucleotide probes specific for each cDNA class hybridized to 6.5-kilobase mRNAs; furthermore, hybridization of probe specific for one class was not blocked by probe specific for the other. Antibodies raised against a synthetic SP1-encoded dodecapeptide specifically recognized the 170-kDa form of Topo II, while antibodies raised against the corresponding SP11-encoded dodecapeptide, or a second unique SP11-encoded tridecapeptide, selectively recognized the 180-kDa form of Topo II. These data provide genetic and immunochemical evidence for two Topo II isozymes

  6. Quality of life philosophy II: what is a human being?

    Science.gov (United States)

    Ventegodt, Søren; Andersen, Niels Jørgen; Kromann, Maximilian; Merrick, Joav

    2003-12-01

    The human being is a complex matter and many believe that just trying to understand life and what it means to be human is a futile undertaking. We believe that we have to try to understand life and get a grip on the many faces of life, because it can be of great value to us to learn to recognize the fundamental principles of how life is lived to the fullest. Learning to recognize the good and evil forces of life helps us to make use of the good ones. To be human is to balance between hundreds of extremes. Sometimes we have to avoid these extremes, but at other times it seems we should pursue them, to better understand life. With our roots in medicine, we believe in the importance of love for better health. The secret of the heart is when reason and feelings meet and we become whole. Where reason is balanced perfectly by feelings and where mind and body come together in perfect unity, a whole new quality emerges, a quality that is neither feeling nor reason, but something deeper and more complete. In this paper, we outline only enough biology to clarify what the fundamental inner conflicts are about. The insight into these conflicts gives us the key to a great deal of the problems of life. To imagine pleasures greater than sensual pleasures seems impossible to most people. What could such a joy possibly be? But somewhere deep in life exists the finest sweetness, the greatest quality in life, the pure joy of being alive that emerges when we are fully present and life is in balance. This deep joy of life is what we call experiencing the meaning of life.

  7. Quality of Life Philosophy II: What is a Human Being?

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt

    2003-01-01

    Full Text Available The human being is a complex matter and many believe that just trying to understand life and what it means to be human is a futile undertaking. We believe that we have to try to understand life and get a grip on the many faces of life, because it can be of great value to us to learn to recognize the fundamental principles of how life is lived to the fullest. Learning to recognize the good and evil forces of life helps us to make use of the good ones.To be human is to balance between hundreds of extremes. Sometimes we have to avoid these extremes, but at other times it seems we should pursue them, to better understand life. With our roots in medicine, we believe in the importance of love for better health. The secret of the heart is when reason and feelings meet and we become whole. Where reason is balanced perfectly by feelings and where mind and body come together in perfect unity, a whole new quality emerges, a quality that is neither feeling nor reason, but something deeper and more complete.In this paper, we outline only enough biology to clarify what the fundamental inner conflicts are about. The insight into these conflicts gives us the key to a great deal of the problems of life. To imagine pleasures greater than sensual pleasures seems impossible to most people. What could such a joy possibly be? But somewhere deep in life exists the finest sweetness, the greatest quality in life, the pure joy of being alive that emerges when we are fully present and life is in balance. This deep joy of life is what we call experiencing the meaning of life.

  8. Propuesta de Modelo Teórico que señala las variables de la Mercadotecnia política que influyen en el comportamiento electoral. Caso: Delegación D-II-IPN-7 del SNTE

    OpenAIRE

    Parra Ortega, Viridiana

    2013-01-01

    En Mexico cada vez mas se manejan estrategias de mercadotecnia política para lograr incentivar la desicion del voto, diversas variables que afectan el comportamiento electoral se encuentran inmersas dentro de la aplicación y estudio de la mercadotecnia política, pero no se han determinado las variables de mercadotecnia política que influyen en el comportamiento electoral.A partir de lo anterior el objetivo de esta investigación es: proponer un modelo teórico que señale las variables de mercad...

  9. Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases

    Science.gov (United States)

    2016-01-01

    Several naturally occurring dietary polyphenols with chemopreventive or anticancer properties are topoisomerase II poisons. To identify additional phytochemicals that enhance topoisomerase II-mediated DNA cleavage, a library of 341 Mediterranean plant extracts was screened for activity against human topoisomerase IIα. An extract from Phillyrea latifolia L., a member of the olive tree family, displayed high activity against the human enzyme. On the basis of previous metabolomics studies, we identified several polyphenols (hydroxytyrosol, oleuropein, verbascoside, tyrosol, and caffeic acid) as potential candidates for topoisomerase II poisons. Of these, hydroxytyrosol, oleuropein, and verbascoside enhanced topoisomerase II-mediated DNA cleavage. The potency of these olive metabolites increased 10–100-fold in the presence of an oxidant. Hydroxytyrosol, oleuropein, and verbascoside displayed hallmark characteristics of covalent topoisomerase II poisons. (1) The activity of the metabolites was abrogated by a reducing agent. (2) Compounds inhibited topoisomerase II activity when they were incubated with the enzyme prior to the addition of DNA. (3) Compounds were unable to poison a topoisomerase IIα construct that lacked the N-terminal domain. Because hydroxytyrosol, oleuropein, and verbascoside are broadly distributed across the olive family, extracts from the leaves, bark, and fruit of 11 olive tree species were tested for activity against human topoisomerase IIα. Several of the extracts enhanced enzyme-mediated DNA cleavage. Finally, a commercial olive leaf supplement and extra virgin olive oils pressed from a variety of Olea europea subspecies enhanced DNA cleavage mediated by topoisomerase IIα. Thus, olive metabolites appear to act as topoisomerase II poisons in complex formulations intended for human dietary consumption. PMID:26132160

  10. Backpack Weight and the Scaling of the Human Frame - II

    Science.gov (United States)

    O'Shea, Michael J.

    2018-02-01

    The backpack weight a hiker is capable of carrying depends on several factors. These include the hiker's weight, body mass index (BMI), fitness, and training. It can also depend on the terrain on which the hiker travels, e.g., off-trail or on-trail. However, online advice has tended to focus on the hiker's weight and suggests that pack weight should be a certain percentage of the hiker's weight. We developed a model of how the ability of a hiker to carry a backpack depends on the weight of the hiker. Modeling such real-life situations helps grab the attention of students in introductory physics. We have expanded on our earlier idea and present a more sophisticated model of an adult backpacker. In particular, we generalize our model for scaling of the human frame, and investigate how the ability to carry a backpack (within our model) varies with the form of scaling used.

  11. Ética, direitos dos usuários e políticas de humanização da atenção à saúde Ethics, users' rights and policies of humanization of healthcare

    Directory of Open Access Journals (Sweden)

    Paulo Antonio de Carvalho Fortes

    2004-12-01

    Full Text Available O artigo trata da evolução das políticas públicas de humanização dos serviços de saúde no Brasil. No campo da atenção em saúde, o termo humanização tem sido utilizado com diferentes significados e entendimentos, relacionando-o com os direitos dos pacientes e a ética voltada ao respeito ao outro. A partir dos anos 90, a humanização da atenção à saúde vem sendo tratada como política pública, iniciando-se no ambiente hospitalar, e , atualmente, sendo dirigida para todos os níveis de atenção de saúde.The article shows the evolution of public policies of humanization of healthcare in Brazil. Humanization was first related to patients' rights and ethics regarding respect for the others. In the nineties humanization is vieved as a public policies. Nowadays it is oriented to all services of health care.

  12. A role for human mitochondrial complex II in the production of reactive oxygen species in human skin

    Directory of Open Access Journals (Sweden)

    Alasdair Anderson

    2014-01-01

    Full Text Available The mitochondrial respiratory chain is a major generator of cellular oxidative stress, thought to be an underlying cause of the carcinogenic and ageing process in many tissues including skin. Previous studies of the relative contributions of the respiratory chain (RC complexes I, II and III towards production of reactive oxygen species (ROS have focussed on rat tissues and certainly not on human skin which is surprising as this tissue is regularly exposed to UVA in sunlight, a potent generator of cellular oxidative stress. In a novel approach we have used an array of established specific metabolic inhibitors and DHR123 fluorescence to study the relative roles of the mitochondrial RC complexes in cellular ROS production in 2 types of human skin cells. These include additional enhancement of ROS production by exposure to physiological levels of UVA. The effects within epidermal and dermal derived skin cells are compared to other tissue cell types as well as those harbouring a compromised mitochondrial status (Rho-zero A549. The results show that the complex II inhibitor, TTFA, was the only RC inhibitor to significantly increase UVA-induced ROS production in both skin cell types (P<0.05 suggesting that the role of human skin complex II in terms of influencing ROS production is more important than previously thought particularly in comparison to liver cells. Interestingly, two-fold greater maximal activity of complex II enzyme was observed in both skin cell types compared to liver (P<0.001. The activities of RC enzymes appear to decrease with increasing age and telomere length is correlated with ageing. Our study showed that the level of maximal complex II activity was higher in the MRC5/hTERT (human lung fibroblasts transfected with telomerase cells than the corresponding wild type cells (P=0.0012 which can be considered (in terms of telomerase activity as models of younger and older cells respectively.

  13. Pvu-II RFLP at the human lipoprotein lipase (LPL) gene locus

    Energy Technology Data Exchange (ETDEWEB)

    Li, S; Oka, K; Galton, D; Stocks, J

    1988-03-25

    Human lipoprotein lipase (LPL) cDNA, 1.6 Kbp, was isolated from human adipose cDNA library and subcloned into Bam HI site of pIB131. Pvu-II identifies a two allele polymorphism with bands at 7.0 Kb, 4.4 Kb and 2.5 Kb. The frequency was studied in 34 caucasians. The gene was assigned to 8p22. Co-dominant inheritance was demonstrated in a 2 generation family.

  14. Legalidad islámica y legitimidad política en el Califato de Córdoba: la proclamación de Hišām II

    Directory of Open Access Journals (Sweden)

    García Sanjuán, Alejandro

    2008-06-01

    Full Text Available This article deals with the process of proclamation as Caliph of Cordoba of Hišām, son and next-in-line to al-Ḥakam II, when he was scarcely eleven years old. Two problems are analyzed in relation to this aspect. On the one hand, from a legal point of view, it is brought into question the lawfulness of the government of an under age in the classical Islamic societies. On the other hand, the political crisis produced by the proclamation of Hišām as a consequence of the opposition to his proclamation in certain juridical and palatine circles. In this context, Ibn Abī ‘Āmir, the future Almanzor, managed to usurp the political authority, pushing aside the caliph and making in that way the caliphal institution fall into disrepute. As a result, the proclamation of Hišām constitutes the first stage of the crisis of the Cordoban caliphate, which finally led to its collapse.

    Este artículo aborda el proceso de proclamación como califa de Córdoba de Hišām, hijo y sucesor de al-Ḥakam II, cuando era todavía un niño de apenas once años. En relación con este aspecto, se analizan dos problemas. Desde el punto de vista jurídico, la cuestión de la legalidad del gobierno de un menor de edad en las sociedades islámicas clásicas. Por otro lado, la crisis política que la proclamación de Hišām desencadenó, debido a las resistencias que generaba en ciertos medios palatinos y jurídicos su minoría. En este contexto, Ibn Abī ‘Āmir, futuro Almanzor, logró usurpar el ejercicio del poder, marginando por completo al califa y provocando con ello el descrédito de la institución califal. Por todo ello, la proclamación de Hišām constituye la primera fase en la crisis del califato de Córdoba, que acabó desembocando en su abolición.

  15. Identification and characterization of the human type II collagen gene (COL2A1).

    NARCIS (Netherlands)

    K.S.E. Cheah (Kathryn); N.G. Stoker; J.R. Griffin; F.G. Grosveld (Frank); E. Solomon

    1985-01-01

    textabstractThe gene contained in the human cosmid clone CosHcol1, previously designated an alpha 1(I) collagen-like gene, has now been identified. CosHcol1 hybridizes strongly to a single 5.9-kilobase mRNA species present only in tissue in which type II collagen is expressed. DNA sequence analysis

  16. Human Rights and Peace Audit on Partition in South Asia - Phase II ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    3 févr. 2009 ... Human Rights and Peace Audit on Partition in South Asia - Phase II. In South Asia, people's social, political and cultural aspirations often get articulated as movements for territorially defined political change. Very often, these movements find resolution in partition or in an ethnic group/nationality getting ...

  17. Casein kinase II is elevated in solid human tumours and rapidly proliferating non-neoplastic tissue

    DEFF Research Database (Denmark)

    Münstermann, U; Fritz, G; Seitz, G

    1990-01-01

    Protein kinase CKII (i.e. casein kinase II, CKII, NII) is expressed at a higher level in rapidly proliferating tissues and in solid human tumours (e.g. colorectal carcinomas) when compared to the corresponding non-neoplastic colorectal mucosa. This could be shown by (a) Western blotting of cellular...

  18. Isolation and characterization of recombinant human casein kinase II subunits alpha and beta from bacteria

    DEFF Research Database (Denmark)

    Grankowski, N; Boldyreff, B; Issinger, O G

    1991-01-01

    cDNA encoding the casein kinase II (CKII) subunits alpha and beta of human origin were expressed in Escherichia coli using expression vector pT7-7. Significant expression was obtained with E. coli BL21(DE3). The CKII subunits accounted for approximately 30% of the bacterial protein; however, most...

  19. Cinco anos da política nacional de humanização: trajetória de uma política pública Five years of the National Policy of Humanization: the trajectory of a public policy

    Directory of Open Access Journals (Sweden)

    Dário Frederico Pasche

    2011-11-01

    Full Text Available O artigo apresenta o cenário de emergência e a trajetória da Política Nacional de Humanização HumanizaSUS, que como política pública foi construída para enfrentar e superar os desafios enunciados pela sociedade brasileira quanto à qualidade e à dignidade no cuidado em saúde; redesenhar e articular iniciativas de humanização do SUS e enfrentar problemas no campo da gestão e da organização do trabalho em saúde. Destacando-a como política pública, os autores analisam suas principais apostas e ofertas teórico-metodológicas para o enfrentamento de problemas na gestão e nas práticas de atenção em saúde, apontando para a necessidade de se combinar estratégias nos planos macro e micropolítico, sem dissociá-las. A análise enfoca mudanças na composição e nas estratégias de ação, as quais incluem a mobilização social, o apoio a instâncias de gestão, os serviços e as equipes de saúde e o desenvolvimento de processos de formação de apoiadores institucionais. Apresenta alguns resultados obtidos nos seus primeiros cinco anos de existência, bem como limites e perspectivas, considerando o desafio da Política de Humanização do SUS se constituir efetivamente em política pública, o que não pode ser alcançado sem a mobilização das forças sociais que se agenciam para além do Estado.This article presents the context of the emergence and implementation of the National Policy of Humanization (NPH, which was devised as a public policy to address and overcome the challenges perceived by Brazilian society regarding the quality and dignity of healthcare. The aims include redesigning and joint initiatives for the humanization of care, and providing solutions for problems in the field of management and organization of the health workforce. Highlighting it as a public policy, the authors analyze the main focus and theoretical and methodological approaches to cope with problems in management and practice of healthcare

  20. Studies of the labelling of human serum albumin with 99mTc using Sn(II) tartrate and Sn(II)Cl2 as reducing agents

    International Nuclear Information System (INIS)

    El-Kolaly, M.T.; El-Asrag, H.A.; El-Wetery, A.S.; El-Mohty, A.A.

    1990-01-01

    A comparative study has been carried out on the effect of Sn(II) tartrate and Sn(II)Cl 2 on the labelling efficiency and tissue distribution of 99m Tc-human serum albumin. The effect of reductant content, reaction time (incubation time), albumin content, pH, and ascorbic acid on the efficiency of labelling and the tissue distribution of the labelled albumin has been investigated. The percentage of labelling was determined by paper and thin layer radiochromatography. Ascorbic acid shows no effect on either labelling efficiency or tissue distribution of 99m Tc-HSA prepared by Sn(II) tartrate or Sn(II)Cl 2 . (author)

  1. Production and X-ray crystallographic analysis of fully deuterated human carbonic anhydrase II

    Energy Technology Data Exchange (ETDEWEB)

    Budayova-Spano, Monika [European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France); Institut Laue-Langevin, 6 Rue Jules Horowitz, BP 156, 38042 Grenoble (France); Fisher, S. Zoë [Department of Biochemistry and Molecular Biology, PO Box 100245, University of Florida, Gainesville, FL 32610 (United States); Dauvergne, Marie-Thérèse [European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France); Agbandje-McKenna, Mavis [Department of Biochemistry and Molecular Biology, PO Box 100245, University of Florida, Gainesville, FL 32610 (United States); Silverman, David N. [Department of Pharmacology and Therapeutics, PO Box 100267, University of Florida, Gainesville, FL 32610 (United States); Myles, Dean A. A. [European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France); Oak Ridge National Laboratory, PO Box 2008, Oak Ridge, TN 37831 (United States); McKenna, Robert, E-mail: rmckenna@ufl.edu [Department of Biochemistry and Molecular Biology, PO Box 100245, University of Florida, Gainesville, FL 32610 (United States); European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France)

    2006-01-01

    This article reports the production, crystallization and X-ray structure determination of perdeuterated human carbonic anhydrase (HCA II). The refined structure is shown to be highly isomorphous with hydrogenated HCA II, especially with regard to the active site architecture and solvent network. Human carbonic anhydrase II (HCA II) is a zinc metalloenzyme that catalyzes the reversible hydration and dehydration of carbon dioxide and bicarbonate, respectively. The rate-limiting step in catalysis is the intramolecular transfer of a proton between the zinc-bound solvent (H{sub 2}O/OH{sup −}) and the proton-shuttling residue His64. This distance (∼7.5 Å) is spanned by a well defined active-site solvent network stabilized by amino-acid side chains (Tyr7, Asn62, Asn67, Thr199 and Thr200). Despite the availability of high-resolution (∼1.0 Å) X-ray crystal structures of HCA II, there is currently no definitive information available on the positions and orientations of the H atoms of the solvent network or active-site amino acids and their ionization states. In preparation for neutron diffraction studies to elucidate this hydrogen-bonding network, perdeuterated HCA II has been expressed, purified, crystallized and its X-ray structure determined to 1.5 Å resolution. The refined structure is highly isomorphous with hydrogenated HCA II, especially with regard to the active-site architecture and solvent network. This work demonstrates the suitability of these crystals for neutron macromolecular crystallography.

  2. Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A.

    Science.gov (United States)

    Ji, Rong; Lee, Clement M; Gonzales, Linda W; Yang, Yi; Aksoy, Mark O; Wang, Ping; Brailoiu, Eugen; Dun, Nae; Hurford, Matthew T; Kelsen, Steven G

    2008-06-01

    Chemokine receptors control several fundamental cellular processes in both hematopoietic and structural cells, including directed cell movement, i.e., chemotaxis, cell differentiation, and proliferation. We have previously demonstrated that CXCR3, the chemokine receptor expressed by Th1/Tc1 inflammatory cells present in the lung, is also expressed by human airway epithelial cells. In airway epithelial cells, activation of CXCR3 induces airway epithelial cell movement and proliferation, processes that underlie lung repair. The present study examined the expression and function of CXCR3 in human alveolar type II pneumocytes, whose destruction causes emphysema. CXCR3 was present in human fetal and adult type II pneumocytes as assessed by immunocytochemistry, immunohistochemistry, and Western blotting. CXCR3-A and -B splice variant mRNA was present constitutively in cultured type II cells, but levels of CXCR3-B greatly exceeded CXCR3-A mRNA. In cultured type II cells, I-TAC, IP-10, and Mig induced chemotaxis. Overexpression of CXCR3-A in the A549 pneumocyte cell line produced robust chemotactic responses to I-TAC and IP-10. In contrast, I-TAC did not induce chemotactic responses in CXCR3-B and mock-transfected cells. Finally, I-TAC increased cytosolic Ca(2+) and activated the extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B kinases only in CXCR3-A-transfected cells. These data indicate that the CXCR3 receptor is expressed by human type II pneumocytes, and the CXCR3-A splice variant mediates chemotactic responses possibly through Ca(2+) activation of both mitogen-activated protein kinase and PI 3-kinase signaling pathways. Expression of CXCR3 in alveolar epithelial cells may be important in pneumocyte repair from injury.

  3. Human action contribution to ET-RR-II reactor systems unstems unavailability

    International Nuclear Information System (INIS)

    Sabek, M.G.

    2001-01-01

    This paper gives a study on the human action contribution to the systems unavailability of ET-RR-II reactor as a result of the test and maintenance procedures. The human contribution is expressed in terms of Fussel-Vesely importance which is defined by the probability that event is contributing to system failure (unavailability). The human error basic events contribution was analyzed for all initiating events and systems fault trees. The calculations result shows a high contribution value (61%) for the human error to systems unavailability. This means that the operator and the maintenance people should be highly qualified trained. Moreover, there should be programs for continuous training. Also, the procedures of tests and maintenance should be in a simple way and clear in order to minimize the contribution of the human errors. The calculations were done using the IRRAS cods

  4. Proviral HIV-genome-wide and pol-gene specific zinc finger nucleases: usability for targeted HIV gene therapy.

    Science.gov (United States)

    Wayengera, Misaki

    2011-07-22

    Infection with HIV, which culminates in the establishment of a latent proviral reservoir, presents formidable challenges for ultimate cure. Building on the hypothesis that ex-vivo or even in-vivo abolition or disruption of HIV-gene/genome-action by target mutagenesis or excision can irreversibly abrogate HIV's innate fitness to replicate and survive, we previously identified the isoschizomeric bacteria restriction enzymes (REases) AcsI and ApoI as potent cleavers of the HIV-pol gene (11 and 9 times in HIV-1 and 2, respectively). However, both enzymes, along with others found to cleave across the entire HIV-1 genome, slice (SX) at palindromic sequences that are prevalent within the human genome and thereby pose the risk of host genome toxicity. A long-term goal in the field of R-M enzymatic therapeutics has thus been to generate synthetic restriction endonucleases with longer recognition sites limited in specificity to HIV. We aimed (i) to assemble and construct zinc finger arrays and nucleases (ZFN) with either proviral-HIV-pol gene or proviral-HIV-1 whole-genome specificity respectively, and (ii) to advance a model for pre-clinically testing lentiviral vectors (LV) that deliver and transduce either ZFN genotype. First, we computationally generated the consensus sequences of (a) 114 dsDNA-binding zinc finger (Zif) arrays (ZFAs or ZifHIV-pol) and (b) two zinc-finger nucleases (ZFNs) which, unlike the AcsI and ApoI homeodomains, possess specificity to >18 base-pair sequences uniquely present within the HIV-pol gene (ZifHIV-polFN). Another 15 ZFNs targeting >18 bp sequences within the complete HIV-1 proviral genome were constructed (ZifHIV-1FN). Second, a model for constructing lentiviral vectors (LVs) that deliver and transduce a diploid copy of either ZifHIV-polFN or ZifHIV-1FN chimeric genes (termed LV- 2xZifHIV-polFN and LV- 2xZifHIV-1FN, respectively) is proposed. Third, two preclinical models for controlled testing of the safety and efficacy of either of these

  5. Detection of human papillomavirus in pterygium and conjunctival papilloma by hybrid capture II and PCR assays.

    Science.gov (United States)

    Takamura, Y; Kubo, E; Tsuzuki, S; Akagi, Y

    2008-11-01

    To elucidate the putative role of human papillomavirus (HPV) infection in pterygium and conjunctival papilloma. Hybrid capture II (HC-II) and polymerase chain reaction (PCR) assays were performed to detect HPV in pterygium (42 samples obtained from 40 patients) and conjunctival papilloma (8 samples from 6 patients). The amount of HPV DNA was evaluated by measurement of relative light units (RLUs) on a luminometer. All papilloma samples were positive for HPV DNA by PCR and HC-II. The RLU values for specimens of recurrent and re-recurrent papilloma were markedly higher than those for specimens of primary lesions. HPV was detected by PCR in 2 of 42 (4.8%) beta-globin-positive pterygium specimens, whereas HC-II showed that HPV was negative in all pterygium samples. Our results support the hypothesis that HPV DNA is associated with the pathogenesis of conjunctival papilloma, but not pterygium. RLU measurement by HC-II may serve as a marker for evaluating the activity of HPV in conjunctival tumours.

  6. The E5 protein of human papillomavirus type 16 perturbs MHC class II antigen maturation in human foreskin keratinocytes treated with interferon-γ

    International Nuclear Information System (INIS)

    Zhang Benyue; Li Ping; Wang Exing; Brahmi, Zacharie; Dunn, Kenneth W.; Blum, Janice S.; Roman, Ann

    2003-01-01

    Major histocompatibility complex (MHC) class II antigens are expressed on human foreskin keratinocytes (HFKs) following exposure to interferon gamma. The expression of MHC class II proteins on the cell surface may allow keratinocytes to function as antigen-presenting cells and induce a subsequent immune response to virus infection. Invariant chain (Ii) is a chaperone protein which plays an important role in the maturation of MHC class II molecules. The sequential degradation of Ii within acidic endocytic compartments is a key process required for the successful loading of antigenic peptide onto MHC class II molecules. Since human papillomavirus (HPV) 16 E5 can inhibit the acidification of late endosomes in HFKs, the E5 protein may be able to affect proper peptide loading onto the MHC class II molecule. To test this hypothesis, HFKs were infected with either control virus or a recombinant virus expressing HPV16 E5 and the infected cells were subsequently treated with interferon-γ. ELISAs revealed a decrease of MHC class II expression on the surface of E5-expressing cells compared with control virus-infected cells after interferon treatment. Western blot analysis showed that, in cells treated with interferon gamma, E5 could prevent the breakdown of Ii and block the formation of peptide-loaded, SDS-stable mature MHC class II dimers, correlating with diminished surface MHC class II expression. These data suggest that HPV16 E5 may be able to decrease immune recognition of infected keratinocytes via disruption of MHC class II protein function

  7. Distribution of class ii major histocompatibility complex antigenexpressing cells in human dental pulp with carious lesions

    Directory of Open Access Journals (Sweden)

    Tetiana Haniastuti

    2012-09-01

    Full Text Available Background: Dental caries is a bacterial infection which causes destruction of the hard tissues of the tooth. Exposure of the dentin to the oral environment as a result of caries inevitably results in a cellular response in the pulp. The major histocompatibility complex (MHC is a group of genes that code for cell-surface histocompatibility antigens. Cells expressing class II MHC molecules participate in the initial recognition and the processing of antigenic substances to serve as antigen-presenting cells. Purpose: The aim of the study was to elucidate the alteration in the distribution of class II MHC antigen-expressing cells in human dental pulp as carious lesions progressed toward the pulp. Methods: Fifteen third molars with caries at the occlusal site at various stages of decay and 5 intact third molars were extracted and used in this study. Before decalcifying with 10% EDTA solution (pH 7.4, all the samples were observed by micro-computed tomography to confirm the lesion condition three-dimensionally. The specimens were then processed for cryosection and immunohistochemistry using an anti-MHC class II monoclonal antibody. Results: Class II MHC antigen-expressing cells were found both in normal and carious specimens. In normal tooth, the class II MHC-immunopositive cells were observed mainly at the periphery of the pulp tissue. In teeth with caries, class II MHC-immunopositive cells were located predominantly subjacent to the carious lesions. As the caries progressed, the number of class II MHC antigen-expressing cells was increased. Conclusion: The depth of carious lesions affects the distribution of class II MHC antigen-expressing cells in the dental pulp.Latar belakang: Karies merupakan penyakit infeksi bakteri yang mengakibatkan destruksi jaringan keras gigi. Dentin yang terbuka akibat karies akan menginduksi respon imun seluler pada pulpa. Kompleks histokompatibilitas utama (MHC merupakan sekumpulan gen yang mengkode histokompatibilitas

  8. An Integrated Human System Interaction (HSI) Framework for Human-Agent Team Collaboration, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — As space missions become more complex and as mission demands increase, robots, human-robot mixed initiative teams and software autonomy applications are needed to...

  9. MHC Class II and CD9 in Human Eosinophils Localize to Detergent-Resistant Membrane Microdomains

    Science.gov (United States)

    Akuthota, Praveen; Melo, Rossana C. N.; Spencer, Lisa A.

    2012-01-01

    Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and colocalization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In granulocyte-macrophage colony-stimulating factor–stimulated human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross-linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent methyl-β-cyclodextrin decreased eosinophil surface expression of HLA-DR and CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the first electron microscopy data of the ultrastructural immunolocalization of CD9 in human eosinophils. Disruption of HLA-DR–containing DRMs decreased the ability of superantigen-loaded human eosinophils to stimulate CD4+ T-cell activation (CD69 expression), proliferation, and cytokine production. Our results, which demonstrate that eosinophil MHC Class II localizes to DRMs in association with CD9 in a functionally significant manner, represent a novel insight into the organization of the antigen presentation complex of human eosinophils. PMID:21885678

  10. MHC Class II and CD9 in human eosinophils localize to detergent-resistant membrane microdomains.

    Science.gov (United States)

    Akuthota, Praveen; Melo, Rossana C N; Spencer, Lisa A; Weller, Peter F

    2012-02-01

    Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and colocalization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In granulocyte-macrophage colony-stimulating factor-stimulated human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross-linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent methyl-β-cyclodextrin decreased eosinophil surface expression of HLA-DR and CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the first electron microscopy data of the ultrastructural immunolocalization of CD9 in human eosinophils. Disruption of HLA-DR-containing DRMs decreased the ability of superantigen-loaded human eosinophils to stimulate CD4(+) T-cell activation (CD69 expression), proliferation, and cytokine production. Our results, which demonstrate that eosinophil MHC Class II localizes to DRMs in association with CD9 in a functionally significant manner, represent a novel insight into the organization of the antigen presentation complex of human eosinophils.

  11. Active site of tripeptidyl peptidase II from human erythrocytes is of the subtilisin type

    Energy Technology Data Exchange (ETDEWEB)

    Tomkinson, B.; Wernstedt, C.; Hellman, U.; Zetterqvist, Oe.

    1987-11-01

    The present report presents evidence that the amino acid sequence around the serine of the active site of human tripeptidyl peptidase II is of the subtilisin type. The enzyme from human erythrocytes was covalently labeled at its active site with (/sup 3/H)diisopropyl fluorophosphate, and the protein was subsequently reduced, alkylated, and digested with trypsin. The labeled tryptic peptides were purified by gel filtration and repeated reversed-phase HPLC, and their amino-terminal sequences were determined. Residue 9 contained the radioactive label and was, therefore, considered to be the active serine residue. The primary structure of the part of the active site (residues 1-10) containing this residue was concluded to be Xaa-Thr-Gln-Leu-Met-Asx-Gly-Thr-Ser-Met. This amino acid sequence is homologous to the sequence surrounding the active serine of the microbial peptidases subtilisin and thermitase. These data demonstrate that human tripeptidyl peptidase II represents a potentially distinct class of human peptidases and raise the question of an evolutionary relationship between the active site of a mammalian peptidase and that of the subtilisin family of serine peptidases.

  12. Chymase-dependent generation of angiotensin II from angiotensin-(1-12 in human atrial tissue.

    Directory of Open Access Journals (Sweden)

    Sarfaraz Ahmad

    Full Text Available Since angiotensin-(1-12 [Ang-(1-12] is a non-renin dependent alternate precursor for the generation of cardiac Ang peptides in rat tissue, we investigated the metabolism of Ang-(1-12 by plasma membranes (PM isolated from human atrial appendage tissue from nine patients undergoing cardiac surgery for primary control of atrial fibrillation (MAZE surgical procedure. PM was incubated with highly purified ¹²⁵I-Ang-(1-12 at 37°C for 1 h with or without renin-angiotensin system (RAS inhibitors [lisinopril for angiotensin converting enzyme (ACE, SCH39370 for neprilysin (NEP, MLN-4760 for ACE2 and chymostatin for chymase; 50 µM each]. ¹²⁵I-Ang peptide fractions were identified by HPLC coupled to an inline γ-detector. In the absence of all RAS inhibitor, ¹²⁵I-Ang-(1-12 was converted into Ang I (2±2%, Ang II (69±21%, Ang-(1-7 (5±2%, and Ang-(1-4 (2±1%. In the absence of all RAS inhibitor, only 22±10% of ¹²⁵I-Ang-(1-12 was unmetabolized, whereas, in the presence of the all RAS inhibitors, 98±7% of ¹²⁵I-Ang-(1-12 remained intact. The relative contribution of selective inhibition of ACE and chymase enzyme showed that ¹²⁵I-Ang-(1-12 was primarily converted into Ang II (65±18% by chymase while its hydrolysis into Ang II by ACE was significantly lower or undetectable. The activity of individual enzyme was calculated based on the amount of Ang II formation. These results showed very high chymase-mediated Ang II formation (28±3.1 fmol × min⁻¹ × mg⁻¹, n = 9 from ¹²⁵I-Ang-(1-12 and very low or undetectable Ang II formation by ACE (1.1±0.2 fmol×min⁻¹ × mg⁻¹. Paralleling these findings, these tissues showed significant content of chymase protein that by immunocytochemistry were primarily localized in atrial cardiac myocytes. In conclusion, we demonstrate for the first time in human cardiac tissue a dominant role of cardiac chymase in the formation of Ang II from Ang-(1-12.

  13. c-Jun binds the N terminus of human TAF(II)250 to derepress RNA polymerase II transcription in vitro.

    Science.gov (United States)

    Lively, T N; Ferguson, H A; Galasinski, S K; Seto, A G; Goodrich, J A

    2001-07-06

    c-Jun is an oncoprotein that activates transcription of many genes involved in cell growth and proliferation. We studied the mechanism of transcriptional activation by human c-Jun in a human RNA polymerase II transcription system composed of highly purified recombinant and native transcription factors. Transcriptional activation by c-Jun depends on the TATA-binding protein (TBP)-associated factor (TAF) subunits of transcription factor IID (TFIID). Protein-protein interaction assays revealed that c-Jun binds with high specificity to the largest subunit of human TFIID, TAF(II)250. The region of TAF(II)250 bound by c-Jun lies in the N-terminal 163 amino acids. This same region of TAF(II)250 binds to TBP and represses its interaction with TATA boxes, thereby decreasing DNA binding by TFIID. We hypothesized that c-Jun is capable of derepressing the effect of the TAF(II)250 N terminus on TFIID-driven transcription. In support of this hypothesis, we found that c-Jun increased levels of TFIID-driven transcription in vitro when added at high concentrations to a DNA template lacking activator protein 1 (AP-1) sites. Moreover, c-Jun blocked the repression of TBP DNA binding caused by the N terminus of TAF(II)250. In addition to revealing a mechanism by which c-Jun activates transcription, our studies provide the first evidence that an activator can bind directly to the N terminus of TAF(II)250 to derepress RNA polymerase II transcription in vitro.

  14. The impact of the human DNA topoisomerase II C-terminal domain on activity.

    Directory of Open Access Journals (Sweden)

    Emma L Meczes

    2008-03-01

    Full Text Available Type II DNA topoisomerases (topos are essential enzymes needed for the resolution of topological problems that occur during DNA metabolic processes. Topos carry out an ATP-dependent strand passage reaction whereby one double helix is passed through a transient break in another. Humans have two topoII isoforms, alpha and beta, which while enzymatically similar are differentially expressed and regulated, and are thought to have different cellular roles. The C-terminal domain (CTD of the enzyme has the most diversity, and has been implicated in regulation. We sought to investigate the impact of the CTD domain on activity.We have investigated the role of the human topoII C-terminal domain by creating constructs encoding C-terminally truncated recombinant topoIIalpha and beta and topoIIalpha+beta-tail and topoIIbeta+alpha-tail chimeric proteins. We then investigated function in vivo in a yeast system, and in vitro in activity assays. We find that the C-terminal domain of human topoII isoforms is needed for in vivo function of the enzyme, but not needed for cleavage activity. C-terminally truncated enzymes had similar strand passage activity to full length enzymes, but the presence of the opposite C-terminal domain had a large effect, with the topoIIalpha-CTD increasing activity, and the topoIIbeta-CTD decreasing activity.In vivo complementation data show that the topoIIalpha C-terminal domain is needed for growth, but the topoIIbeta isoform is able to support low levels of growth without a C-terminal domain. This may indicate that topoIIbeta has an additional localisation signal. In vitro data suggest that, while the lack of any C-terminal domain has little effect on activity, the presence of either the topoIIalpha or beta C-terminal domain can affect strand passage activity. Data indicates that the topoIIbeta-CTD may be a negative regulator. This is the first report of in vitro data with chimeric human topoIIs.

  15. As políticas e a gestão de recursos humanos em saúde: 1984 a 1995 Health human resources politics and management: from 1984 to 1995

    Directory of Open Access Journals (Sweden)

    Mario Roberto Dal Poz

    2001-12-01

    Full Text Available A implantação do Sistema Único de Saúde - SUS, aprovada pela Constituição Federal de 1988, representou uma inovação política cuja característica central é a descentralização. Esta reforma do sistema de saúde vem transferindo aos municípios a missão de gestor único dos serviços de saúde no seu nível, numa inflexão nas normas e práticas até então vigentes. Este artigo trata das repercussões da reforma do sistema de saúde sobre as políticas de recursos humanos, focalizando o Estado do Rio de Janeiro e o nível municipal. Busca-se explicar algumas de suas insuficiências e contribuir para estabelecer novas bases e modelos para a política e gestão de recursos humanos no SUS. A pesquisa, que serviu de base ao artigo e à tese de doutorado, foi realizada no Estado do Rio de Janeiro e nos Municípios de Niterói e Angra dos Reis, que estavam enquadrados na categoria de gestão semiplena, segundo a Norma Operacional SUS Ol/93. Utilizando-se metodologia qualitativa foram feitas observações, coleta de documentos e entrevistas com gestores, técnicos e dirigentes de órgãos de representação de interesses dos trabalhadores, en quanto atores privilegiados das políticas e do processo de gestão de recursos humanos. Para a análise foi feito um recorte em torno de duas categorias: objetos do processo de regulação do trabalho e filosofia de gestão. Na primeira categoria foram consideradas como variáveis as definições dos planos de cargos e carreiras, da remuneração e da jornada de trabalho e, para a segunda, a participação na gestão, o processo de negociação e os programas de capacitação.The implantation of lhe SUS, approved by the 1988 Federal Constitution, represented a political innovation whose main characteristic is decentralization. This reform of the heallh system gave the municipalities the mission of' being the only manager of heallh system on their levels, in a shift in the rules and practices so far in

  16. As políticas activas e passivas do mercado de trabalho

    OpenAIRE

    Novo, Álvaro; Centeno, Mário

    2008-01-01

    A generalidade dos países utiliza políticas destinadas a minorar os custos sociais e individuais do desemprego. Os economistas classificam estas políticas do mercado de trabalho em dois grupos: (i) políticas activas e (ii) políticas passivas. As primeiras têm como objectivo dotar os desempregados com as qualificações necessárias para minimizar a duração do desemprego, enquanto as segundas visam garantir uma fonte de rendimento durante o período de desemprego, sendo particularmente úteis para ...

  17. Functional substitution for TAF(II)250 by a retroposed homolog that is expressed in human spermatogenesis.

    Science.gov (United States)

    Wang, P Jeremy; Page, David C

    2002-09-15

    TAF(II)250, the largest subunit of the general transcription factor TFIID, is expressed from the human X chromosome, at least in somatic cells. In male meiosis, however, the sex chromosomes are transcriptionally silenced, while the autosomes remain active. How then are protein-encoding genes transcribed during human male meiosis? Here we present a novel autosomal human gene, TAF1L, which is homologous to TAF(II)250 and is expressed specifically in the testis, apparently in germ cells. We hypothesize that during male meiosis, transcription of protein-encoding genes relies upon TAF1L as a functional substitute for TAF(II)250. Like TAF(II)250, the human TAF1L protein can bind directly to TATA-binding protein, an essential component of TFIID. Most importantly, transfection with human TAF1L rescued the temperature-sensitive lethality of a hamster cell line mutant in TAF(II)250. TAF1L lacks introns and evidently arose by retroposition of a processed TAF(II)250 mRNA during primate evolution. The observation that TAF1L can functionally replace TAF(II)250 provides experimental support for the hypothesis that during male meiosis, autosomes provide cellular functions usually supplied by the X chromosome in somatic cells.

  18. Biochemical characterization of individual human glycosylated pro-insulin-like growth factor (IGF)-II and big-IGF-II isoforms associated with cancer.

    Science.gov (United States)

    Greenall, Sameer A; Bentley, John D; Pearce, Lesley A; Scoble, Judith A; Sparrow, Lindsay G; Bartone, Nicola A; Xiao, Xiaowen; Baxter, Robert C; Cosgrove, Leah J; Adams, Timothy E

    2013-01-04

    Insulin-like growth factor II (IGF-II) is a major embryonic growth factor belonging to the insulin-like growth factor family, which includes insulin and IGF-I. Its expression in humans is tightly controlled by maternal imprinting, a genetic restraint that is lost in many cancers, resulting in up-regulation of both mature IGF-II mRNA and protein expression. Additionally, increased expression of several longer isoforms of IGF-II, termed "pro" and "big" IGF-II, has been observed. To date, it is ambiguous as to what role these IGF-II isoforms have in initiating and sustaining tumorigenesis and whether they are bioavailable. We have expressed each individual IGF-II isoform in their proper O-glycosylated format and established that all bind to the IGF-I receptor and both insulin receptors A and B, resulting in their activation and subsequent stimulation of fibroblast proliferation. We also confirmed that all isoforms are able to be sequestered into binary complexes with several IGF-binding proteins (IGFBP-2, IGFBP-3, and IGFBP-5). In contrast to this, ternary complex formation with IGFBP-3 or IGFBP-5 and the auxillary protein, acid labile subunit, was severely diminished. Furthermore, big-IGF-II isoforms bound much more weakly to purified ectodomain of the natural IGF-II scavenging receptor, IGF-IIR. IGF-II isoforms thus possess unique biological properties that may enable them to escape normal sequestration avenues and remain bioavailable in vivo to sustain oncogenic signaling.

  19. Biochemical Characterization of Individual Human Glycosylated pro-Insulin-like Growth Factor (IGF)-II and big-IGF-II Isoforms Associated with Cancer

    Science.gov (United States)

    Greenall, Sameer A.; Bentley, John D.; Pearce, Lesley A.; Scoble, Judith A.; Sparrow, Lindsay G.; Bartone, Nicola A.; Xiao, Xiaowen; Baxter, Robert C.; Cosgrove, Leah J.; Adams, Timothy E.

    2013-01-01

    Insulin-like growth factor II (IGF-II) is a major embryonic growth factor belonging to the insulin-like growth factor family, which includes insulin and IGF-I. Its expression in humans is tightly controlled by maternal imprinting, a genetic restraint that is lost in many cancers, resulting in up-regulation of both mature IGF-II mRNA and protein expression. Additionally, increased expression of several longer isoforms of IGF-II, termed “pro” and “big” IGF-II, has been observed. To date, it is ambiguous as to what role these IGF-II isoforms have in initiating and sustaining tumorigenesis and whether they are bioavailable. We have expressed each individual IGF-II isoform in their proper O-glycosylated format and established that all bind to the IGF-I receptor and both insulin receptors A and B, resulting in their activation and subsequent stimulation of fibroblast proliferation. We also confirmed that all isoforms are able to be sequestered into binary complexes with several IGF-binding proteins (IGFBP-2, IGFBP-3, and IGFBP-5). In contrast to this, ternary complex formation with IGFBP-3 or IGFBP-5 and the auxillary protein, acid labile subunit, was severely diminished. Furthermore, big-IGF-II isoforms bound much more weakly to purified ectodomain of the natural IGF-II scavenging receptor, IGF-IIR. IGF-II isoforms thus possess unique biological properties that may enable them to escape normal sequestration avenues and remain bioavailable in vivo to sustain oncogenic signaling. PMID:23166326

  20. Regulated gene expression in cultured type II cells of adult human lung.

    Science.gov (United States)

    Ballard, Philip L; Lee, Jae W; Fang, Xiaohui; Chapin, Cheryl; Allen, Lennell; Segal, Mark R; Fischer, Horst; Illek, Beate; Gonzales, Linda W; Kolla, Venkatadri; Matthay, Michael A

    2010-07-01

    Alveolar type II cells have multiple functions, including surfactant production and fluid clearance, which are critical for lung function. Differentiation of type II cells occurs in cultured fetal lung epithelial cells treated with dexamethasone plus cAMP and isobutylmethylxanthine (DCI) and involves increased expression of 388 genes. In this study, type II cells of human adult lung were isolated at approximately 95% purity, and gene expression was determined (Affymetrix) before and after culturing 5 days on collagen-coated dishes with or without DCI for the final 3 days. In freshly isolated cells, highly expressed genes included SFTPA/B/C, SCGB1A, IL8, CXCL2, and SFN in addition to ubiquitously expressed genes. Transcript abundance was correlated between fetal and adult cells (r = 0.88), with a subset of 187 genes primarily related to inflammation and immunity that were expressed >10-fold higher in adult cells. During control culture, expression increased for 8.1% of expressed genes and decreased for approximately 4% including 118 immune response and 10 surfactant-related genes. DCI treatment promoted lamellar body production and increased expression of approximately 3% of probed genes by > or =1.5-fold; 40% of these were also induced in fetal cells. Highly induced genes (> or =10-fold) included PGC, ZBTB16, DUOX1, PLUNC, CIT, and CRTAC1. Twenty-five induced genes, including six genes related to surfactant (SFTPA/B/C, PGC, CEBPD, and ADFP), also had decreased expression during control culture and thus are candidates for hormonal regulation in vivo. Our results further define the adult human type II cell molecular phenotype and demonstrate that a subset of genes remains hormone responsive in cultured adult cells.

  1. Chemical Rescue of Enzymes: Proton Transfer in Mutants of Human Carbonic Anhydrase II

    Science.gov (United States)

    Maupin, C. Mark; Castillo, Norberto; Taraphder, Srabani; Tu, Chingkuang; McKenna, Robert; Silverman, David N.; Voth, Gregory A.

    2011-01-01

    In human carbonic anhydrase II (HCA II) the mutation of position 64 from histidine to alanine (H64A) disrupts the rate limiting proton transfer (PT) event, resulting in a reduction of the catalytic activity of the enzyme as compared to the wild-type. Potential of mean force (PMF) calculations utilizing the multistate empirical valence bond (MS-EVB) methodology for H64A HCA II give a PT free energy barrier significantly higher than that found in the wild-type enzyme. This high barrier, determined in the absence of exogenous buffer and assuming no additional ionizable residues in the PT pathway, indicates the likelihood of alternate enzyme pathways that utilize either ionizable enzyme residues (self-rescue) and/or exogenous buffers (chemical rescue). It has been shown experimentally that the catalytic activity of H64A HCA II can be chemically rescued to near wild type levels by the addition of the exogenous buffer 4-methylimidazole (4MI). Crystallographic studies have identified two 4MI binding sites, yet site specific mutations intended to disrupt 4MI binding have demonstrated these sites to be non-productive. In the present work MS-EVB simulations show that binding of 4MI near Thr199 in the H64A HCA II mutant, a binding site determined by NMR spectroscopy, results in a viable chemical rescue pathway. Additional viable rescue pathways are also identified where 4MI acts as a proton transport intermediary from the active site to ionizable residues on the rim of the active site, revealing a probable mode of action for the chemical rescue pathway PMID:21452838

  2. [Effect of Mn(II) on the error-prone DNA polymerase iota activity in extracts from human normal and tumor cells].

    Science.gov (United States)

    Lakhin, A V; Efremova, A S; Makarova, I V; Grishina, E E; Shram, S I; Tarantul, V Z; Gening, L V

    2013-01-01

    The DNA polymerase iota (Pol iota), which has some peculiar features and is characterized by an extremely error-prone DNA synthesis, belongs to the group of enzymes preferentially activated by Mn2+ instead of Mg2+. In this work, the effect of Mn2+ on DNA synthesis in cell extracts from a) normal human and murine tissues, b) human tumor (uveal melanoma), and c) cultured human tumor cell lines SKOV-3 and HL-60 was tested. Each group displayed characteristic features of Mn-dependent DNA synthesis. The changes in the Mn-dependent DNA synthesis caused by malignant transformation of normal tissues are described. It was also shown that the error-prone DNA synthesis catalyzed by Pol iota in extracts of all cell types was efficiently suppressed by an RNA aptamer (IKL5) against Pol iota obtained in our work earlier. The obtained results suggest that IKL5 might be used to suppress the enhanced activity of Pol iota in tumor cells.

  3. Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II.

    OpenAIRE

    Zanger, U M; Hauri, H P; Loeper, J; Homberg, J C; Meyer, U A

    1988-01-01

    In a subgroup of children with chronic active hepatitis, circulating autoantibodies occur that bind to liver and kidney endoplasmic reticulum (anti-liver/kidney microsome antibody type I or anti-LKM1). Anti-LKM1 titers follow the severity of the disease and the presence of these antibodies serves as a diagnostic marker for this autoimmune hepatitis type II. We demonstrate that anti-LKM1 IgGs specifically inhibit the hydroxylation of bufuralol in human liver microsomes. Using two assay systems...

  4. Angiotensin II upregulates the expression of placental growth factor in human vascular endothelial cells and smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Guo Yingqiang

    2010-05-01

    Full Text Available Abstract Background Atherosclerosis is now recognized as a chronic inflammatory disease. Angiotensin II (Ang II is a critical factor in inflammatory responses, which promotes the pathogenesis of atherosclerosis. Placental growth factor (PlGF is a member of the vascular endothelial growth factor (VEGF family cytokines and is associated with inflammatory progress of atherosclerosis. However, the potential link between PlGF and Ang II has not been investigated. In the current study, whether Ang II could regulate PlGF expression, and the effect of PlGF on cell proliferation, was investigated in human vascular endothelial cells (VECs and smooth muscle cells (VSMCs. Results In growth-arrested human VECs and VSMCs, Ang II induced PlGF mRNA expression after 4 hour treatment, and peaked at 24 hours. 10-6 mol/L Ang II increased PlGF protein production after 8 hour treatment, and peaked at 24 hours. Stimulation with Ang II also induced mRNA expression of VEGF receptor-1 and -2(VEGFR-1 and -2 in these cells. The Ang II type I receptor (AT1R antagonist blocked Ang II-induced PlGF gene expression and protein production. Several intracellular signals elicited by Ang II were involved in PlGF synthesis, including activation of protein kinase C, extracellular signal-regulated kinase 1/2 (ERK1/2 and PI3-kinase. A neutralizing antibody against PlGF partially inhibited the Ang II-induced proliferation of VECs and VSMCs. However, this antibody showed little effect on the basal proliferation in these cells, whereas blocking antibody of VEGF could suppress both basal and Ang II-induced proliferation in VECs and VSMCs. Conclusion Our results showed for the first time that Ang II could induce the gene expression and protein production of PlGF in VECs and VSMCs, which might play an important role in the pathogenesis of vascular inflammation and atherosclerosis.

  5. DNA polymerase iota (Pol ι) promotes invasion and metastasis of esophageal squamous cell carcinoma.

    Science.gov (United States)

    Zou, Shitao; Shang, Zeng-Fu; Liu, Biao; Zhang, Shuyu; Wu, Jinchang; Huang, Min; Ding, Wei-Qun; Zhou, Jundong

    2016-05-31

    DNA polymerase iota (Pol ι) is an error-prone DNA polymerase involved in translesion DNA synthesis (TLS) that contributes to the accumulation of DNA mutations. We recently showed that Pol ι is overexpressed in human esophageal squamous cell cancer (ESCC) tissues which promotes ESCC' progression. The present study was aimed at investigating the molecular mechanisms by which Pol ι enhances the invasiveness and metastasis of ESCC cells. We found that the expression of Pol ι is significantly higher in ESCCs with lymph node metastasis compared to those without lymph node metastasis. Kaplan-Meier analysis revealed an inverse correlation between Pol ι expression and patient prognosis. The expression levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two essential regulators of cells' invasiveness, were positively associated with Pol ι expression in ESCC tissues. Ectopic expression of Pol ι enhanced the motility and invasiveness of ESCC cells as evaluated by wound-healing and transwell assays, respectively. A xenograft nude mouse model showed that Pol ι promotes the colonization of ESCC cells in the liver, lung and kidney. Signaling pathway analysis identified the JNK-AP-1 cascade as a mediator of the Pol ι-induced increase in the expression of MMP-2/9 and enhancement of ESCC progression. These data demonstrate the underlying mechanism by which Pol ι promotes ESCC progression, suggesting that Pol ι is a potential novel prognostic biomarker and therapeutic target for ESCC.

  6. Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system.

    Science.gov (United States)

    McLaughlin, M; Albertini, D F; Wallace, W H B; Anderson, R A; Telfer, E E

    2018-03-01

    Can complete oocyte development be achieved from human ovarian tissue containing primordial/unilaminar follicles and grown in vitro in a multi-step culture to meiotic maturation demonstrated by the formation of polar bodies and a Metaphase II spindle? Development of human oocytes from primordial/unilaminar stages to resumption of meiosis (Metaphase II) and emission of a polar body was achieved within a serum free multi-step culture system. Complete development of oocytes in vitro has been achieved in mouse, where in vitro grown (IVG) oocytes from primordial follicles have resulted in the production of live offspring. Human oocytes have been grown in vitro from the secondary/multi-laminar stage to obtain fully grown oocytes capable of meiotic maturation. However, there are no reports of a culture system supporting complete growth from the earliest stages of human follicle development through to Metaphase II. Ovarian cortical biopsies were obtained with informed consent from women undergoing elective caesarean section (mean age: 30.7 ± 1.7; range: 25-39 years, n = 10). Laboratory setting. Ovarian biopsies were dissected into thin strips, and after removal of growing follicles were cultured in serum free medium for 8 days (Step 1). At the end of this period secondary/multi-laminar follicles were dissected from the strips and intact follicles 100-150 μm in diameter were selected for further culture. Isolated follicles were cultured individually in serum free medium in the presence of 100 ng/ml of human recombinant Activin A (Step 2). Individual follicles were monitored and after 8 days, cumulus oocyte complexes (COCs) were retrieved by gentle pressure on the cultured follicles. Complexes with complete cumulus and adherent mural granulosa cells were selected and cultured in the presence of Activin A and FSH on membranes for a further 4 days (Step 3). At the end of Step 3, complexes containing oocytes >100 μm diameter were selected for IVM in SAGE medium (Step 4) then

  7. The Multi-Attribute Task Battery II (MATB-II) Software for Human Performance and Workload Research: A User's Guide

    Science.gov (United States)

    Santiago-Espada, Yamira; Myer, Robert R.; Latorella, Kara A.; Comstock, James R., Jr.

    2011-01-01

    The Multi-Attribute Task Battery (MAT Battery). is a computer-based task designed to evaluate operator performance and workload, has been redeveloped to operate in Windows XP Service Pack 3, Windows Vista and Windows 7 operating systems.MATB-II includes essentially the same tasks as the original MAT Battery, plus new configuration options including a graphical user interface for controlling modes of operation. MATB-II can be executed either in training or testing mode, as defined by the MATB-II configuration file. The configuration file also allows set up of the default timeouts for the tasks, the flow rates of the pumps and tank levels of the Resource Management (RESMAN) task. MATB-II comes with a default event file that an experimenter can modify and adapt

  8. Human leukocyte antigen class II susceptibility conferring alleles among non-insulin dependent diabetes mellitus patients

    International Nuclear Information System (INIS)

    Tipu, H.N.; Ahmed, T.A.; Bashir, M.M.

    2010-01-01

    To determine the frequency of Human Leukocyte Antigen (HLA) class II susceptibility conferring alleles among type 2 Diabetes mellitus patients, in comparison with healthy controls. Cross-sectional comparative study. Patients with non-insulin dependent Diabetes mellitus meeting World Health Organization criteria were studied. These were compared with age and gender matched healthy control subjects. For each subject (patients as well as controls), DNA was extracted from ethylene diamine tetra-acetate sample and HLA class II DRB1 typing was carried out at allele group level (DRB1*01-DRB1*16) by sequence specific primers. Human leukocyte antigen DRB1 type was determined by agarose gel electrophoresis and results were recorded. Frequencies were determined as number of an allele divided by total number of alleles per group; p-value was computed using Pearson's chi-square test. Among the 100 patients, there were 63 males and 37 females with 68 controls. A total of 13 different HLA DRB1 alleles were detected, with DRB1*15 being the commonest in both the groups. The allele DRB1*13 had statistically significant higher frequency in patient group as compared to controls (p 0.005). HLA DRB1*13 was found with a significantly increased frequency in non-insulin dependent Diabetes mellitus. (author)

  9. Pharmacological inhibition of dynamin II reduces constitutive protein secretion from primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Maaike Kockx

    Full Text Available Dynamins are fission proteins that mediate endocytic and exocytic membrane events and are pharmacological therapeutic targets. These studies investigate whether dynamin II regulates constitutive protein secretion and show for the first time that pharmacological inhibition of dynamin decreases secretion of apolipoprotein E (apoE and several other proteins constitutively secreted from primary human macrophages. Inhibitors that target recruitment of dynamin to membranes (MiTMABs or directly target the GTPase domain (Dyngo or Dynole series, dose- and time- dependently reduced the secretion of apoE. SiRNA oligo's targeting all isoforms of dynamin II confirmed the involvement of dynamin II in apoE secretion. Inhibition of secretion was not mediated via effects on mRNA or protein synthesis. 2D-gel electrophoresis showed that inhibition occurred after apoE was processed and glycosylated in the Golgi and live cell imaging showed that inhibited secretion was associated with reduced post-Golgi movement of apoE-GFP-containing vesicles. The effect was not restricted to macrophages, and was not mediated by the effects of the inhibitors on microtubules. Inhibition of dynamin also altered the constitutive secretion of other proteins, decreasing the secretion of fibronectin, matrix metalloproteinase 9, Chitinase-3-like protein 1 and lysozyme but unexpectedly increasing the secretion of the inflammatory mediator cyclophilin A. We conclude that pharmacological inhibitors of dynamin II modulate the constitutive secretion of macrophage apoE as a class effect, and that their capacity to modulate protein secretion may affect a range of biological processes.

  10. Development of a ECOREA-II code for human exposures from radionuclides through food chain

    International Nuclear Information System (INIS)

    Yoo, D. H.; Choi, Y. H.

    2001-01-01

    The release of radionuclides from nuclear facilities following an accident into air results in human exposures through two pathways. One is direct human exposures by inhalation or dermal absorption of these radionucles. Another is indirect human exposures through food chain which includes intakes of plant products such as rice, vegetables from contaiminated soil and animal products such as meet, milk and eggs feeded by contaminated grasses or plants on the terrestial surface. This study presents efforts of the development of a computer code for the assessment of the indirect human exposure through such food chains. The purpose of ECOREA-II code is to develop appropriate models suitable for a specific soil condition in Korea based on previous experimental efforts and to provide a more user-friendly environment such as GUI for the use of the code. Therefore, the current code, when more fully developed, is expected to increase the understanding of environmental safety assessment of nuclear facilities following an accident and provide a reasonable regulatory guideline with respecte to food safety issues

  11. Política científico-tecnológica y la gestión institucional en el Centro de Desarrollo de las Ciencias Sociales y Humanísticas en Salud

    Directory of Open Access Journals (Sweden)

    María Elena Macías Llanes

    Full Text Available Este trabajo tiene como objetivo valorar la contribución del Centro de Desarrollo de las Ciencias Sociales y Humanísticas en Salud a las Ciencias Sociales y Humanísticas en el sector de la Salud de Camagüey, desde la contextualización de la política científica cubana en la proyección estratégica de la entidad. En el mismo se expone la trayectoria de la gestión de la actividad científico-tecnológica del centro. Se utilizó la revisión de los documentos y resultados generados por la entidad y trabajos publicados acerca de la actividad científica. Se concluye que el centro es una institución pertinente y con sus resultados impacta en la formación integral de los recursos humanos y en el desarrollo del enfoque social de los problemas de salud.

  12. Papel dos profissionais de saúde na política de humanização hospitalar Papel de los profesionales de salud en la política de humanización hospitalaria The role of health professionals in policies regarding hospital humanization

    Directory of Open Access Journals (Sweden)

    Roberta Araújo Mota

    2006-08-01

    Full Text Available O interesse por este tema surgiu a partir de uma reflexão sobre o papel do profissional de saúde nos atendimentos realizados no ambiente hospitalar, tendo como meta transmitir para esses profissionais informações sobre os cuidados de saúde de uma maneira mais simples e humanizada, e assim levar o bem-estar a todos. O governo adota uma política legal e ética com relação à saúde no país, possuindo um papel fundamental no processo de humanização. Com a proposta de melhorar a qualidade do atendimento nos hospitais, percebemos que estas atividades requerem tempo e conscientização tanto dos profissionais como do governo e pessoas envolvidas no sistema de saúde. Diante desta situação, o psicólogo surge com o papel de resgatar o ser humano para além de sua dimensão físico-biológica e situá-lo num contexto maior de sentido e significado nas suas dimensões psíquicas e sociais.El interés por este tema surgió a partir de una reflexión sobre el papel del profesional de salud en los atendimientos realizados en el ambiente hospitalario, teniendo como meta transmitir a estos profesionales informaciones sobre los cuidados de salud de una manera más simple y humanizada, y así, proporcionar bienestar a todos. El Gobierno adopta una política legal y ética con relación a la salud en el país, teniendo un papel fundamental en el proceso de humanización. Con la propuesta de mejorar la calidad del atendimiento en los hospitales, percibimos que estas actividades requieren tiempo y concienciación, tanto de los profesionales como del Gobierno y personas involucradas en el sistema de salud. Ante esta situación, el psicólogo surge con el papel de rescatar el ser humano más allá de su dimensión físico-biológica y ubicarlo en un contexto mayor de sentido y significado en sus dimensiones psíquicas y sociales.The interest on this theme emerged from a reflection on the role of health professionals in relation to the attendance carried

  13. Política y Administración Provincial. La Diputación de Sevilla durante la Dictadura de Primo de Rivera y la II República (1923-1936).

    OpenAIRE

    Ponce Alberca, Julio

    2016-01-01

    Desde la perspectiva de fines del siglo XX, los regímenes políticos de la España de los años veinte y treinta aparecen como una secuencia de ensayos en respuesta a la profunda crisis sufrida por el sistema de la Restauración (1876-1923). Bajo ese enfoque, la Segunda República (1931-1936) se nos muestra inscrita en el esfuerzo por encontrar una nueva alternativa tras el fracaso de la Dictadura primorriverista (1923-1930) y las dictablandas del genera...

  14. Bases teórico-políticas del bloque ibérico : la relación peninsular en la fase de inflexión de la II Guerra Mundial, 1942-1945

    OpenAIRE

    Juan Carlos Jiménez Redondo

    1994-01-01

    Al abordar las relaciones entre España y Portugal cualquiera que sea el momento histórico escogido, resulta siempre sorprendente comprobar cómo una frontera política, ausente de impedimentos naturales, ha podido levantar un muro difícilmente franqueable entre ambas comunidades. De hecho, la noción de vecindad tiene en el caso hispano-portugués una dimensión estática, basada en el hecho de una contigüedad geográfica, que contrasta con la dimensión dinámica propia de una relac...

  15. Localization and characterization of angiotensin II receptor binding and angiotensin converting enzyme in the human medulla oblongata.

    Science.gov (United States)

    Allen, A M; Chai, S Y; Clevers, J; McKinley, M J; Paxinos, G; Mendelsohn, F A

    1988-03-08

    Angiotensin II receptor and angiotensin converting enzyme distributions in the human medulla oblongata were localised by quantitative in vitro autoradiography. Angiotensin II receptors were labelled with the antagonist analogue 125I-[Sar1, Ile8] AII while angiotensin converting enzyme was labelled with 125I-351A, a derivative of the specific converting enzyme inhibitor, lisinopril. Angiotensin II receptor binding and angiotensin converting enzyme are present in high concentrations in the nucleus of the solitary tract, the dorsal motor nucleus of vagus, the rostral and caudal ventrolateral reticular nucleus, and in a band connecting the dorsal and ventral regions. In the rostral and caudal ventrolateral reticular nucleus, angiotensin II receptors are distributed in a punctate pattern that registers with neuronal cell bodies. The distribution and density of these cell bodies closely resemble those of catecholamine-containing neurones mapped by others. In view of the known interactions of angiotensin II with both central and peripheral catecholamine-containing neurons of laboratory animals, the current anatomical findings suggest similar interactions between these neuroactive compounds in the human central nervous system. The presence of angiotensin II receptors and angiotensin converting enzyme in the nucleus of the solitary tract, dorsal motor nucleus of vagus, and rostral and caudal ventrolateral reticular nucleus demonstrates sites for central angiotensin II to exert its known actions on vasopressin release and autonomic functions including blood pressure control. These data also suggest a possible interaction between angiotensin II and central catecholeminergic systems.

  16. Fluctuations of pol I and fibrillarin contents of the nucleoli.

    Science.gov (United States)

    Hornáček, M; Kováčik, L; Mazel, T; Cmarko, D; Bártová, E; Raška, I; Smirnov, E

    2017-07-04

    Nucleoli are formed on the basis of ribosomal DNA (rDNA) clusters called Nucleolus Organizer Regions (NORs). Each NOR contains multiple genes coding for RNAs of the ribosomal particles. The prominent components of the nucleolar ultrastructure, fibrillar centers (FC) and dense fibrillar components (DFC), together compose FC/DFC units. These units are centers of rDNA transcription by RNA polymerase I (pol I), as well as the early processing events, in which an essential role belongs to fibrillarin. Each FC/DFC unit probably corresponds to a single transcriptionally active gene. In this work, we transfected human-derived cells with GFP-RPA43 (subunit of pol I) and RFP-fibrillarin. Following changes of the fluorescent signals in individual FC/DFC units, we found two kinds of kinetics: 1) the rapid fluctuations with periods of 2-3 min, when the pol I and fibrillarin signals oscillated in anti-phase manner, and the intensities of pol I in the neighboring FC/DFC units did not correlate. 2) fluctuations with periods of 10 to 60 min, in which pol I and fibrillarin signals measured in the same unit did not correlate, but pol I signals in the units belonging to different nucleoli were synchronized. Our data indicate that a complex pulsing activity of transcription as well as early processing is common for ribosomal genes.

  17. Nickel (II)-induced cytotoxicity and apoptosis in human proximal tubule cells through a ROS- and mitochondria-mediated pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yi-Fen; Shyu, Huey-Wen [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Chang, Yi-Chuang [Department of Nursing, Fooyin University, Kaohsiung, Taiwan (China); Tseng, Wei-Chang [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Huang, Yeou-Lih [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Lin, Kuan-Hua; Chou, Miao-Chen; Liu, Heng-Ling [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Chen, Chang-Yu, E-mail: mt037@mail.fy.edu.tw [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)

    2012-03-01

    Nickel compounds are known to be toxic and carcinogenic in kidney and lung. In this present study, we investigated the roles of reactive oxygen species (ROS) and mitochondria in nickel (II) acetate-induced cytotoxicity and apoptosis in the HK-2 human renal cell line. The results showed that the cytotoxic effects of nickel (II) involved significant cell death and DNA damage. Nickel (II) increased the generation of ROS and induced a noticeable reduction of mitochondrial membrane potential (MMP). Analysis of the sub-G1 phase showed a significant increase in apoptosis in HK-2 cells after nickel (II) treatment. Pretreatment with N-acetylcysteine (NAC) not only inhibited nickel (II)-induced cell death and DNA damage, but also significantly prevented nickel (II)-induced loss of MMP and apoptosis. Cell apoptosis triggered by nickel (II) was characterized by the reduced protein expression of Bcl-2 and Bcl-xL and the induced the protein expression of Bad, Bcl-Xs, Bax, cytochrome c and caspases 9, 3 and 6. The regulation of the expression of Bcl-2-family proteins, the release of cytochrome c and the activation of caspases 9, 3 and 6 were inhibited in the presence of NAC. These results suggest that nickel (II) induces cytotoxicity and apoptosis in HK-2 cells via ROS generation and that the mitochondria-mediated apoptotic signaling pathway may be involved in the positive regulation of nickel (II)-induced renal cytotoxicity.

  18. Nickel (II)-induced cytotoxicity and apoptosis in human proximal tubule cells through a ROS- and mitochondria-mediated pathway

    International Nuclear Information System (INIS)

    Wang, Yi-Fen; Shyu, Huey-Wen; Chang, Yi-Chuang; Tseng, Wei-Chang; Huang, Yeou-Lih; Lin, Kuan-Hua; Chou, Miao-Chen; Liu, Heng-Ling; Chen, Chang-Yu

    2012-01-01

    Nickel compounds are known to be toxic and carcinogenic in kidney and lung. In this present study, we investigated the roles of reactive oxygen species (ROS) and mitochondria in nickel (II) acetate-induced cytotoxicity and apoptosis in the HK-2 human renal cell line. The results showed that the cytotoxic effects of nickel (II) involved significant cell death and DNA damage. Nickel (II) increased the generation of ROS and induced a noticeable reduction of mitochondrial membrane potential (MMP). Analysis of the sub-G1 phase showed a significant increase in apoptosis in HK-2 cells after nickel (II) treatment. Pretreatment with N-acetylcysteine (NAC) not only inhibited nickel (II)-induced cell death and DNA damage, but also significantly prevented nickel (II)-induced loss of MMP and apoptosis. Cell apoptosis triggered by nickel (II) was characterized by the reduced protein expression of Bcl-2 and Bcl-xL and the induced the protein expression of Bad, Bcl-Xs, Bax, cytochrome c and caspases 9, 3 and 6. The regulation of the expression of Bcl-2-family proteins, the release of cytochrome c and the activation of caspases 9, 3 and 6 were inhibited in the presence of NAC. These results suggest that nickel (II) induces cytotoxicity and apoptosis in HK-2 cells via ROS generation and that the mitochondria-mediated apoptotic signaling pathway may be involved in the positive regulation of nickel (II)-induced renal cytotoxicity.

  19. Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II.

    Science.gov (United States)

    Zanger, U M; Hauri, H P; Loeper, J; Homberg, J C; Meyer, U A

    1988-11-01

    In a subgroup of children with chronic active hepatitis, circulating autoantibodies occur that bind to liver and kidney endoplasmic reticulum (anti-liver/kidney microsome antibody type I or anti-LKM1). Anti-LKM1 titers follow the severity of the disease and the presence of these antibodies serves as a diagnostic marker for this autoimmune hepatitis type II. We demonstrate that anti-LKM1 IgGs specifically inhibit the hydroxylation of bufuralol in human liver microsomes. Using two assay systems with different selectivity for the two cytochrome P-450 isozymes catalyzing bufuralol metabolism in human liver, we show that anti-LKM1 exclusively recognizes cytochrome P-450db1. Immunopurification of the LKM1 antigen from solubilized human liver microsomes resulted in an electrophoretically homogenous protein that had the same molecular mass (50 kDa) as purified P-450db1 and an identical N-terminal amino acid sequence. Recognition of both purified P-450db1 and the immunoisolated protein on western blots by several monoclonal antibodies confirmed the identity of the LKM1 antigen with cytochrome P-450db1. Cytochrome P-450db1 has been identified as the target of a common genetic polymorphism of drug oxidation. However, the relationship between the polymorphic cytochrome P-450db1 and the appearance of anti-LKM1 autoantibodies as well as their role in the pathogenesis of chronic active hepatitis remains speculative.

  20. Antigen presentation and MHC class II expression by human esophageal epithelial cells: role in eosinophilic esophagitis.

    Science.gov (United States)

    Mulder, Daniel J; Pooni, Aman; Mak, Nanette; Hurlbut, David J; Basta, Sameh; Justinich, Christopher J

    2011-02-01

    Professional antigen-presenting cells (APCs) play a crucial role in initiating immune responses. Under pathological conditions, epithelial cells at mucosal surfaces act as nonprofessional APCs, thereby regulating immune responses at the site of exposure. Epithelial cells in the esophagus may contribute to the pathogenesis of eosinophilic esophagitis (EoE) by presenting antigens on the major histocompatibility complex (MHC) class II. Our goal was to demonstrate the ability of esophageal epithelial cells to process and present antigens on the MHC class II system and to investigate the contribution of epithelial cell antigen presentation to EoE. Immunohistochemistry detected HLA-DR, CD80, and CD86 expression and enzyme-linked immunosorbent assay detected interferon-γ (IFNγ) in esophageal biopsies. Antigen presentation was studied using the human esophageal epithelial cell line HET-1A by reverse transcriptase-PCR, flow cytometry, and confocal microscopy. T helper cell lymphocyte proliferation was assessed by flow cytometry and IL-2 secretion. IFNγ and MHC class II were increased in mucosa of patients with EoE. IFNγ increased mRNA of HLA-DP, HLA-DQ, HLA-DR, and CIITA in HET-1A cells. HET-1A engulfed cell debris and processed ovalbumin. HET-1A cells expressed HLA-DR after IFNγ treatment. HET-1A stimulated T helper cell activation. In this study, we demonstrated the ability of esophageal epithelial cells to act as nonprofessional APCs in the presence of IFNγ. Esophageal epithelial cell antigen presentation may contribute to the pathophysiology of eosinophilic esophagitis. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Real-time dynamics of RNA Polymerase II clustering in live human cells

    Science.gov (United States)

    Cisse, Ibrahim

    2014-03-01

    Transcription is the first step in the central dogma of molecular biology, when genetic information encoded on DNA is made into messenger RNA. How this fundamental process occurs within living cells (in vivo) is poorly understood,[1] despite extensive biochemical characterizations with isolated biomolecules (in vitro). For high-order organisms, like humans, transcription is reported to be spatially compartmentalized in nuclear foci consisting of clusters of RNA Polymerase II, the enzyme responsible for synthesizing all messenger RNAs. However, little is known of when these foci assemble or their relative stability. We developed an approach based on photo-activation localization microscopy (PALM) combined with a temporal correlation analysis, which we refer to as tcPALM. The tcPALM method enables the real-time characterization of biomolecular spatiotemporal organization, with single-molecule sensitivity, directly in living cells.[2] Using tcPALM, we observed that RNA Polymerase II clusters form transiently, with an average lifetime of 5.1 (+/- 0.4) seconds. Stimuli affecting transcription regulation yielded orders of magnitude changes in the dynamics of the polymerase clusters, implying that clustering is regulated and plays a role in the cells ability to effect rapid response to external signals. Our results suggest that the transient crowding of enzymes may aid in rate-limiting steps of genome regulation.

  2. Conformational effects on the circular dichroism of Human Carbonic Anhydrase II: a multilevel computational study.

    Directory of Open Access Journals (Sweden)

    Tatyana G Karabencheva-Christova

    Full Text Available Circular Dichroism (CD spectroscopy is a powerful method for investigating conformational changes in proteins and therefore has numerous applications in structural and molecular biology. Here a computational investigation of the CD spectrum of the Human Carbonic Anhydrase II (HCAII, with main focus on the near-UV CD spectra of the wild-type enzyme and it seven tryptophan mutant forms, is presented and compared to experimental studies. Multilevel computational methods (Molecular Dynamics, Semiempirical Quantum Mechanics, Time-Dependent Density Functional Theory were applied in order to gain insight into the mechanisms of interaction between the aromatic chromophores within the protein environment and understand how the conformational flexibility of the protein influences these mechanisms. The analysis suggests that combining CD semi empirical calculations, crystal structures and molecular dynamics (MD could help in achieving a better agreement between the computed and experimental protein spectra and provide some unique insight into the dynamic nature of the mechanisms of chromophore interactions.

  3. Phaeophytins from Thyrsacanthus ramosissimus Moric. with inhibitory activity on human DNA topoisomerase II-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Cabral, Analucia Guedes Silveira; Tenorio-Souza, Fabio Henrique; Moura, Marcelo Dantas; Mota, Sabrina Gondim Ribeiro; Silva Lins, Antonio Claudio da; Dias, Celidarque da Silva; Barbosa-Filho, Jose Maria [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Dept. de Ciencias Frmaceuticas; Giulietti, Ana Maria [Universidade Estadual de Feira de Santana, Feira de Santana, BA (Brazil). Dept. de Ciencias Biologicas; Silva, Tania Maria Sarmento da [Universidade Federal Rural de Pernambuco, Recife, PE (Brazil). Dept. de Ciencias Moleculares; Santos, Creusioni Figueredo dos, E-mail: jbarbosa@ltf.ufpb.br [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Dept. de Biologia Molecular

    2012-07-01

    Our study reports the extraction and isolation of a new phaeophytin derivative 15{sup 1}-hydroxy-(15{sup 1}-S)-porphyrinolactone, designated anamariaine (1) herein, isolated from the chloroform fraction of aerial parts of Thyrsacanthus ramosissimus Moric. along with the known 15{sup 1}-ethoxy-(15{sup 1}-S)-porphyrinolactone (2). These compounds were identified by usual spectroscopic methods. Both compounds were subjected to in vitro (inhibitory activity) tests by means of supercoiled DNA relaxation techniques and were shown to display inhibitory activity against human DNA topoisomerase II-{alpha} at 50 {mu}M. Interconversion of these two pigments under the mild conditions of the isolation techniques should be highly unlikely but cannot be entirely ruled out. (author)

  4. Effects of human serun albumin in some biological properties of rhodium(II complexes

    Directory of Open Access Journals (Sweden)

    Espósito Breno P.

    2000-01-01

    Full Text Available The affinities for human albumin (HSA of five rhodium(II complexes of general formula [Rh2(bridge4] (bridge = acetate, propionate, butyrate, trifluoroacetate and trifluoroacetamidate were determined by spectrophotometry. In the case of the alkylcarboxylates, an inverse correlation of affinity with their liposolubilities was observed. Diffusion of the free or protein-bound complexes into Ehrlich cells in vitro seems to be primarily governed by the hydrophobic character of the complex. The complex [Rh2(tfc4] exhibited affinity towards the protein (K = 214.1 as well as cell partition both in the absence (32.1% and presence (48.6% of HSA. The compound HSA: [Rh2(tfc4] has had its antitumoral action in tumor-bearing Balb-c mice investigated, showing that HSA can be a drug reservoir for the rhodium complex.

  5. Structural elucidation of the hormonal inhibition mechanism of the bile acid cholate on human carbonic anhydrase II

    Energy Technology Data Exchange (ETDEWEB)

    Boone, Christopher D. [University of Florida, PO Box 100267, Gainesville, FL 32610 (United States); Tu, Chingkuang [University of Florida, PO Box 100245, Gainesville, FL 32610 (United States); McKenna, Robert, E-mail: rmckenna@ufl.edu [University of Florida, PO Box 100267, Gainesville, FL 32610 (United States)

    2014-06-01

    The structure of human carbonic anhydrase II in complex with cholate has been determined to 1.54 Å resolution. Elucidation of the novel inhibition mechanism of cholate will aid in the development of a nonsulfur-containing, isoform-specific therapeutic agent. The carbonic anhydrases (CAs) are a family of mostly zinc metalloenzymes that catalyze the reversible hydration/dehydration of CO{sub 2} into bicarbonate and a proton. Human isoform CA II (HCA II) is abundant in the surface epithelial cells of the gastric mucosa, where it serves an important role in cytoprotection through bicarbonate secretion. Physiological inhibition of HCA II via the bile acids contributes to mucosal injury in ulcerogenic conditions. This study details the weak biophysical interactions associated with the binding of a primary bile acid, cholate, to HCA II. The X-ray crystallographic structure determined to 1.54 Å resolution revealed that cholate does not make any direct hydrogen-bond interactions with HCA II, but instead reconfigures the well ordered water network within the active site to promote indirect binding to the enzyme. Structural knowledge of the binding interactions of this nonsulfur-containing inhibitor with HCA II could provide the template design for high-affinity, isoform-specific therapeutic agents for a variety of diseases/pathological states, including cancer, glaucoma, epilepsy and osteoporosis.

  6. Cytotoxicity of Diimine Palladium (II) Complexes of Alkyldithiocarbamate Derivatives on Human Lung, Ovary and Liver Cells.

    Science.gov (United States)

    Aryanpour, Narges; Mansouri-Torshizi, Hassan; Nakhjavan, Maryam; H Shirazi, Farshad

    2012-01-01

    Three new Complexes of formula [pd(bpy)(R-NH-CSS)] Cl (where bpy is 2/2'- bipyridine, and R-NH-CSS is butylamine, hexylamine- and octyamine-dithiocabamate anion) have been synthesized by University of Sistan and Blachostan. These complexes have been characterized by spectroscopic methods such as ultraviolet-visible, infrared and (1)H-NMR as well as conductivity measurements and chemical analysis. In these complexes, each of the dithiocarbamate ligands coordinates to Pd (II) center as bidentate with two sulfur atoms. We have found a 1:1 electrolyte in water conductivity test for the above mentioned compounds. To measure the biologic activity and potential anticancer efficacy of these compounds, they have been compared with cisplatin and its palladium analogue of [Pd (NH3)2 Cl2] on three different cell lines of human hepatocarcinoma HepG2, human ovarian carcinoma OV2008, and human lung adenocarcinoma A549. Clonogenic assay has shown LD50s in the range of 0.131±0.025 to 0.934 ± 0.194 for these compounds on above cell lines. In comparison, cisplatin has shown LD50s of 0.838 ± 0.074, 2.196 ± 0.220, and 2.799 ± 0.733 on OV2008, HepG2 and A549 cell lines, respectively. As a conclusion, above three new complexes have shown higher cytotoxicities compared to cisplatin on three different human cell lines. Based on biological tests, these compounds may potentially be considered as good anticancer candidates for further pharmacological studies.

  7. JC polyomavirus infection is strongly controlled by human leucocyte antigen class II variants.

    Directory of Open Access Journals (Sweden)

    Emilie Sundqvist

    2014-04-01

    Full Text Available JC polyomavirus (JCV carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50-60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA, instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP kits and a reverse PCR sequence-specific oligonucleotide (PCR-SSO method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15 and controls (OR = 0.53, p = 2×10(-5. In contrast, the DQB1*06:03 haplotype was positively associated with JCV sero-status, in Scandinavian MS cases (OR = 1.63, p = 0.006, and controls (OR = 2.69, p = 1×10(-5. The German dataset confirmed these findings (OR = 0.54, p = 1×10(-4 and OR = 1.58, p = 0.03 respectively for these haplotypes. HLA class II restricted immune responses, and hence CD4+ T cell immunity is pivotal for JCV infection control. Alleles within the HLA-DR1*15 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB1*06:03 haplotype show an opposite association. These associations between JC virus antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and

  8. Bases teórico-políticas del bloque ibérico : la relación peninsular en la fase de inflexión de la II Guerra Mundial, 1942-1945

    Directory of Open Access Journals (Sweden)

    Juan Carlos Jiménez Redondo

    1994-01-01

    Full Text Available Al abordar las relaciones entre España y Portugal cualquiera que sea el momento histórico escogido, resulta siempre sorprendente comprobar cómo una frontera política, ausente de impedimentos naturales, ha podido levantar un muro difícilmente franqueable entre ambas comunidades. De hecho, la noción de vecindad tiene en el caso hispano-portugués una dimensión estática, basada en el hecho de una contigüedad geográfica, que contrasta con la dimensión dinámica propia de una relación de vecindad, donde los actores no sólo están unidos geográficamente sino que se da una comunicación y relación efectiva entre ellos.

  9. Hydroxyl Radical Formation from HULIS and Fe(II) Interactions: Fulvic Acid-Fe(II) Complexes in Simulated and Human Lung Fluids

    Science.gov (United States)

    Gonzalez, D.

    2017-12-01

    Inhalation of fine particulate matter (PM2.5) has long been associated with adverse health outcomes. However, the causative agents and underlying mechanisms for these health effects have yet to be identified. One hypothesis is that PM2.5 deposited in the alveoli produce an excess of highly reactive radicals, leading to oxidative stress. The OH radical may be the most physiologically damaging, capable of oxidizing of lipids, proteins and DNA. Due to the variability and uncertainty in PM2.5 composition, the components that contribute to OH formation are not well understood. Soluble Fe is a component of PM2.5that produces OH under physiological conditions. Humic-like substances are water soluble organics found in biomass burning and tobacco smoke. Humic-like substances are capable of binding to Fe and enhancing OH formation, but this chemistry is not well understood. In this work, we use soil derived fulvic acid as a surrogate for Humic-like substances and investigate its effect on OH formation from Fe(II) under conditions relevant to the lungs. We use a fluorescent OH trapping probe, chemical kinetics and thermodynamic modeling to investigate OH formation from fulvic acid and Fe(II) dissolved in simulated and human lung fluids. In simulated lung fluid, we find that fulvic acid binds to Fe(II) and enhances the rate of key reactions that form OH. When fulvic acid is added to human lung fluids containing Fe(II), an enhancement of OH formation is observed. In human lung fluid, fulvic acid and metal binding proteins compete for Fe binding. These metal binding proteins are typically not found in simulated lung fluids. Results show that fulvic acid strongly binds Fe(II) and catalyzes key reactions that form OH in both simulated and human lung fluids. These results may help explain the role of Humic-like substances and Fe in oxidative stress and adverse health outcomes. Furthermore, we suggest that future studies employ simulated lung fluids containing metal binding proteins

  10. Mechanism of selective recruitment of RNA polymerases II and III to snRNA gene promoters.

    Science.gov (United States)

    Dergai, Oleksandr; Cousin, Pascal; Gouge, Jerome; Satia, Karishma; Praz, Viviane; Kuhlman, Tracy; Lhôte, Philippe; Vannini, Alessandro; Hernandez, Nouria

    2018-05-01

    RNA polymerase II (Pol II) small nuclear RNA (snRNA) promoters and type 3 Pol III promoters have highly similar structures; both contain an interchangeable enhancer and "proximal sequence element" (PSE), which recruits the SNAP complex (SNAPc). The main distinguishing feature is the presence, in the type 3 promoters only, of a TATA box, which determines Pol III specificity. To understand the mechanism by which the absence or presence of a TATA box results in specific Pol recruitment, we examined how SNAPc and general transcription factors required for Pol II or Pol III transcription of SNAPc-dependent genes (i.e., TATA-box-binding protein [TBP], TFIIB, and TFIIA for Pol II transcription and TBP and BRF2 for Pol III transcription) assemble to ensure specific Pol recruitment. TFIIB and BRF2 could each, in a mutually exclusive fashion, be recruited to SNAPc. In contrast, TBP-TFIIB and TBP-BRF2 complexes were not recruited unless a TATA box was present, which allowed selective and efficient recruitment of the TBP-BRF2 complex. Thus, TBP both prevented BRF2 recruitment to Pol II promoters and enhanced BRF2 recruitment to Pol III promoters. On Pol II promoters, TBP recruitment was separate from TFIIB recruitment and enhanced by TFIIA. Our results provide a model for specific Pol recruitment at SNAPc-dependent promoters. © 2018 Dergai et al.; Published by Cold Spring Harbor Laboratory Press.

  11. Isolation and characterization of human cDNA clones encoding the α and the α' subunits of casein kinase II

    International Nuclear Information System (INIS)

    Lozeman, F.J.; Litchfield, D.W.; Piening, C.; Takio, Koji; Walsh, K.A.; Krebs, E.G.

    1990-01-01

    Casein kinase II is a widely distributed protein serine/threonine kinase. The holoenzyme appears to be a tetramer, containing two α or α' subunits (or one of each) and two β subunits. Complementary DNA clones encoding the subunits of casein kinase II were isolated from a human T-cell λgt 10 library using cDNA clones isolated from Drosophila melanogasten. One of the human cDNA clones (hT4.1) was 2.2 kb long, including a coding region of 1176 bp preceded by 156 bp (5' untranslated region) and followed by 871 bp (3' untranslated region). The hT4.1 close was nearly identical in size and sequence with a cDNA clone from HepG2 human hepatoma cultured cells. Another of the human T-cell cDNA clones (hT9.1) was 1.8 kb long, containing a coding region of 1053 bp preceded by 171 by (5' untranslated region) and followed by 550 bp (3' untranslated region). Amino acid sequences deduced from these two cDNA clones were about 85% identical. Most of the difference between the two encoded polypeptides was in the carboxy-terminal region, but heterogeneity was distributed throughout the molecules. Partial amino acid sequence was determined in a mixture of α and α' subunits from bovine lung casein kinase II. The bovine sequences aligned with the 2 human cDNA-encoded polypeptides with only 2 discrepancies out of 535 amino acid positions. This confirmed that the two human T-cell cDNA clones encoded the α and α' subunits of casein kinase II. These studies show that there are two distinct catalytic subunits for casein II (α and α') and that the sequence of these subunits is largely conserved between the bovine and the human

  12. BanII dimorphic site located in the third intron of the human apolipoprotein AI (APOA1) gene

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, R T; Kresnak, M T; Frossard, P M

    1988-02-11

    A 0.7kb fragment generated by AvaII digestion of pBL13AI, a 0.965kb full-length human apolipoprotein AI cDNA was cloned into the EcoRI site of pBR322. The apoAI cDNA was isolated from a lambdagt10 human fetal liver cDNA library. BanII (GPuGCPyC) (International Biotechnologies, Inc.) identifies two invariant bands at 1122bp and 417bp, and a single two-allele polymorphism with bands at either 274bp or 452bp. The human apolipoprotein AI-CIII-AIV gene complex has been localized on the long arm of chromosome 11 by Southern blot analysis of human-chinese hamster cell hybrids. Co-dominant segregation has been observed in two families (13 individuals). The BanII restriction map was constructed from DNA sequence data of the human apoAI gene. The 452bp fragment is generated by the loss of a BanII dimorphic site in the third intron of the apoAI gene, between the 178bp and the 274bp fragments.

  13. Biophysical study on the interaction between two palladium(II) complexes and human serum albumin by Multispectroscopic methods

    Energy Technology Data Exchange (ETDEWEB)

    Saeidifar, Maryam, E-mail: saeidifar@merc.ac.ir [Department of Nanotechnology and Advanced Materials, Materials and Energy Research Center, Karaj (Iran, Islamic Republic of); Mansouri-Torshizi, Hassan [Department of Chemistry, University of Sistan and Baluchestan, Zahedan (Iran, Islamic Republic of); Akbar Saboury, Ali [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of)

    2015-11-15

    The interaction of [Pd(bpy)(n-pr-dtc)]Br (I) and ([Pd(phen)(n-pr-dtc)]Br (II) (bpy=2,2′-bipyridine, phen=1,10-phenanthroline and n-pr-dtc=n-propyldithiocarbamate) with human serum albumin (HSA) was investigated using fluorescence, UV–vis absorption and circular dichroism (CD) spectroscopy techniques under simulative physiological conditions (pH=7.4). It was observed that the two complexes interact with HSA via static fluorescence quenching. The thermodynamic parameters indicate that the binding process was spontaneous and that hydrogen bonds and van der Waals forces play a major role in the association of the HSA–Pd(II) complexes. The activation energy (E{sub a}), binding constant (K{sub b}) and number of binding sites (n) of the HSA–Pd(II) complexes were calculated from fluorescence data at 293 K, 303 K and 311 K. The conformational alternations of protein secondary structure in the presence of Pd(II) complexes were demonstrated using synchronous fluorescence, three-dimensional fluorescence spectra, UV–vis absorption and circular dichroism techniques. Furthermore, the apparent distance between donor (HSA) and acceptor (Pd(II) complexes) was determined using fluorescence resonance energy transfer (FRET). The binding studies between these complexes and HSA give us key insights into the transportation, distribution and toxicity of newly design antitumor Pd(II) complexes in human blood. - Highlights: • The HSA binding properties of two Palladium (II) complexes were studied. • Static quenching mechanism is effective in the interaction of HSA with Pd(II) complexes. • Hydrogen bonds and van der Waals forces were involved in the Pd(II) complexes–HSA interaction. • 3D fluorescence was used to study the interaction between two complexes and HSA.

  14. Reproduction in the space environment: Part II. Concerns for human reproduction

    Science.gov (United States)

    Jennings, R. T.; Santy, P. A.

    1990-01-01

    Long-duration space flight and eventual colonization of our solar system will require successful control of reproductive function and a thorough understanding of factors unique to space flight and their impact on gynecologic and obstetric parameters. Part II of this paper examines the specific environmental factors associated with space flight and the implications for human reproduction. Space environmental hazards discussed include radiation, alteration in atmospheric pressure and breathing gas partial pressures, prolonged toxicological exposure, and microgravity. The effects of countermeasures necessary to reduce cardiovascular deconditioning, calcium loss, muscle wasting, and neurovestibular problems are also considered. In addition, the impact of microgravity on male fertility and gamete quality is explored. Due to current constraints, human pregnancy is now contraindicated for space flight. However, a program to explore effective countermeasures to current constraints and develop the required health care delivery capability for extended-duration space flight is suggested. A program of Earth- and space-based research to provide further answers to reproductive questions is suggested.

  15. Isolation of an insulin-like growth factor II cDNA with a unique 5' untranslated region from human placenta

    International Nuclear Information System (INIS)

    Shen, Shujane; Daimon, Makoto; Wang, Chunyeh; Ilan, J.; Jansen, M.

    1988-01-01

    Human insulin-like growth factor II (IGF-II) cDNA from a placental library was isolated and sequenced. The 5' untranslated region (5'-UTR) sequence of this cDNA differs completely from that of adult human liver and has considerable base sequence identity to the same region of an IGF-II cDNA of a rat liver cell line, BRL-3A. Human placental poly(A) + RNA was probed with either the 5'-UTR of the isolated human placental IGF-II cDNA or the 5'-UTR of the IGF-II cDNA obtained from adult human liver. No transcripts were detected by using the 5'-UTR of the adult liver IGF-II as the probe. In contrast, three transcripts of 6.0, 3.2, and 2.2 kilobases were detected by using the 5'-UTR of the placental IGF-II cDNA as the probe or the probe from the coding sequence. A fourth IGF-II transcript of 4.9 kilobases presumably containing a 5'-UTR consisting of a base sequence dissimilar to that of either IGF-II 5'-UTR was apparent. Therefore, IGF-II transcripts detected may be products of alternative splicing as their 5'-UTR sequence is contained within the human IGF-II gene or they may be a consequence of alternative promoter utilization in placenta

  16. 18F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases

    International Nuclear Information System (INIS)

    Yu, Chunjing; Mi, Baoming; Wan, Weixing; Pan, Donghui; Xu, Yuping; Yang, Min; Lang, Lixin; Niu, Gang; Chen, Xiaoyuan

    2015-01-01

    We report the biodistribution and radiation dosimetry of an integrin α v β 3 specific PET tracer 18 F-AlF-NOTA-E[PEG 4 -c(RGDfk)] 2 (denoted as 18 F-Alfatide II). We also assessed the value of 18 F-Alfatide II in patients with brain metastases. A series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of 18 F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with 18 F-FDG (5.55 MBq/kg) and 18 F-Alfatide II. Injection of 18 F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. 18 F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by 18 F-Alfatide II PET, while only ten lesions were visualized by 18 F-FDG, and 13 by CT. F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that 18 F-Alfatide II is feasible for human studies. 18 F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis. (orig.)

  17. Low prevalence of antibodies to human T-lymphotropic virus-I/II among blood donors in eastern Saudi Arabia.

    Science.gov (United States)

    Fawaz, Naglaa A; Tamim, Hala; Almawi, Wassim Y

    2005-04-01

    The seroprevalence of human T-lymphotropic virus (HTLV)-I/II was assessed in 13,443 consecutive blood donors in eastern Saudi Arabia between 1998 and 2001. Screening by enzyme-linked immunosorbent assay (ELISA) and confirmation by Western blot resulted in 8 (0.060%) positive cases, of which 5 (0.056%) belonged to Saudi and 3 (0.113%) to non-Saudi donors. The majority of the HTLV-positive donations (6/8) were for patients, and none had a history of known risk factor for HTLV-I/II transmission. Although the very low prevalence of HTLV-I/II among Saudi donors does not support routine screening, screening of donors from other nationalities may be initiated, especially those from HTLV-I/II endemic areas.

  18. Competitive binding of Chlorin p6 and Dansyl-L-Proline to Sudlow's site II of human serum albumin

    Science.gov (United States)

    Patel, Sunita; Sharma, Kaushal Kishor; Datta, Anindya

    2015-03-01

    The binding of chlorin p6, a model photosensitizer for photodynamic therapy (PDT), to the Sudlow's site II of Human Serum Albumin (HSA) has been monitored by different spectroscopic methods. Displacement of Dansyl-L-Proline (DP) from its conjugate with HSA is manifested in the spectral shift and decrease in its fluorescence intensity as well as the emergence of component with lifetime of 2-3 ns, which is characteristic of free DP. As DP is known to bind specifically to the Sudlow's site II of human serum albumin, its displacement by chlorin p6 indicates the residence of the photosensitizer in the same site, in addition to Sudlow's site I. The binding constants for Sudlow's site II, determined by the stopped-flow technique, are found to be two orders of magnitude smaller than that for Sudlow's site I.

  19. Homotypic aggregation of human cell lines by HLA class II-, class Ia- and HLA-G-specific monoclonal antibodies

    DEFF Research Database (Denmark)

    Odum, Niels; Ledbetter, J A; Martin, P

    1991-01-01

    Major histocompatibility complex (MHC) class II molecules have been implicated in cell adhesion in two ways. In addition to the well-established role of class II antigens in low-affinity adhesion provided by interactions between class II and CD4, recent data indicated that class II may also induce...... adhesion between T and B cells by activating the CD18/CD11a (LFA-1) adhesion pathway. Here we report that monoclonal antibodies (mAb) against HLA-DR (L243, p4.1, HB10a, VI15) and certain broad class II reacting mAb (TU35, TU39), but not anti-DQ (TU22, Leu-10) mAb, induced homotypic aggregation of human...... class II-positive monocytic (I937) and T leukemic (HUT78) tumor cell lines and Epstein-Barr virus (EBV) transformed B-lymphoid cell lines (EBV-LCL). Class II-negative cell lines (U-937 and the EBV-LCL mutant line 616) were not induced to aggregate. An HLA-G-transfected EBV-LCL, 221-AGN...

  20. Identifying Effective Enzyme Activity Targets for Recombinant Class I and Class II Collagenase for Successful Human Islet Isolation

    OpenAIRE

    Balamurugan, Appakalai N.; Green, Michael L.; Breite, Andrew G.; Loganathan, Gopalakrishnan; Wilhelm, Joshua J.; Tweed, Benjamin; Vargova, Lenka; Lockridge, Amber; Kuriti, Manikya; Hughes, Michael G.; Williams, Stuart K.; Hering, Bernhard J.; Dwulet, Francis E.; McCarthy, Robert C.

    2015-01-01

    Isolation following a good manufacturing practice-compliant, human islet product requires development of a robust islet isolation procedure where effective limits of key reagents are known. The enzymes used for islet isolation are critical but little is known about the doses of class I and class II collagenase required for successful islet isolation.

  1. TOPOISOMERASE-I AND TOPOISOMERASE-II ACTIVITY IN HUMAN BREAST, CERVIX, LUNG AND COLON-CANCER

    NARCIS (Netherlands)

    MCLEOD, HL; DOUGLAS, F; OATES, M; SYMONDS, RP; PRAKASH, D; VANDERZEE, AGJ; KAYE, SB; BROWN, R; KEITH, WN

    1994-01-01

    The identification of human DNA topoisomerases as cellular targets for active anti-cancer drugs has stimulated further interest in topoisomerase function in tumour biology. Topoisomerase I and II catalytic activity is detectable in many normal and malignant tissues. However, little is known about

  2. Human insulin-like growth factor II leader 2 mediates internal initiation of translation

    DEFF Research Database (Denmark)

    Pedersen, Susanne; Christiansen, Jan; Hansen, T.O.

    2002-01-01

    Insulin-like growth factor II (IGF-II) is a fetal growth factor, which belongs to the family of insulin-like peptides. During fetal life, the IGF-II gene generates three mRNAs with different 5' untranslated regions (UTRs), but identical coding regions and 3' UTRs. We have shown previously that IG...

  3. Sensitivity and specificity of four assays to detect human T-lymphotropic virus type I or type I/II antibodies

    NARCIS (Netherlands)

    Vrielink, H.; Reesink, H. W.; Zaaijer, H. L.; van der Poel, C. L.; Cuypers, H. T.; Lelie, P. N.

    1996-01-01

    BACKGROUND: Assays that detect human T-lymphotropic virus type I and type II antibody (HTLV-I/II) are widely used in the routine screening of blood donors. STUDY DESIGN AND METHODS: Four commercially available anti-HTLV-I (Fujirebio and Organon Teknika) or -HTLV-I/II assays (Murex and Ortho) were

  4. Human immune responses to H. pylori HLA Class II epitopes identified by immunoinformatic methods.

    Directory of Open Access Journals (Sweden)

    Songhua Zhang

    Full Text Available H. pylori persists in the human stomach over decades and promotes several adverse clinical sequelae including gastritis, peptic ulcers and gastric cancer that are linked to the induction and subsequent evasion of chronic gastric inflammation. Emerging evidence indicates that H. pylori infection may also protect against asthma and some other immune-mediated conditions through regulatory T cell effects outside the stomach. To characterize the complexity of the CD4+ T cell response generated during H. pylori infection, computational methods were previously used to generate a panel of 90 predicted epitopes conserved among H. pylori genomes that broadly cover HLA Class II diversity for maximum population coverage. Here, these sequences were tested individually for their ability to induce in vitro responses in peripheral blood mononuclear cells by interferon-γ ELISpot assay. The average number of spot-forming cells/million PBMCs was significantly elevated in H. pylori-infected subjects over uninfected persons. Ten of the 90 peptides stimulated IFN-γ secretion in the H. pylori-infected group only, whereas two out of the 90 peptides elicited a detectable IFN-γ response in the H. pylori-uninfected subjects but no response in the H. pylori-infected group. Cytokine ELISA measurements performed using in vitro PBMC culture supernatants demonstrated significantly higher levels of TNF-α, IL-2, IL-4, IL-6, IL-10, and TGF-β1 in the H. pylori-infected subjects, whereas IL-17A expression was not related to the subjects H. pylori-infection status. Our results indicate that the human T cell responses to these 90 peptides are generally increased in actively H. pylori-infected, compared with H. pylori-naïve, subjects. This information will improve understanding of the complex immune response to H. pylori, aiding rational epitope-driven vaccine design as well as helping identify other H. pylori epitopes with potentially immunoregulatory effects.

  5. High-throughput sequencing of human plasma RNA by using thermostable group II intron reverse transcriptases

    Science.gov (United States)

    Qin, Yidan; Yao, Jun; Wu, Douglas C.; Nottingham, Ryan M.; Mohr, Sabine; Hunicke-Smith, Scott; Lambowitz, Alan M.

    2016-01-01

    Next-generation RNA-sequencing (RNA-seq) has revolutionized transcriptome profiling, gene expression analysis, and RNA-based diagnostics. Here, we developed a new RNA-seq method that exploits thermostable group II intron reverse transcriptases (TGIRTs) and used it to profile human plasma RNAs. TGIRTs have higher thermostability, processivity, and fidelity than conventional reverse transcriptases, plus a novel template-switching activity that can efficiently attach RNA-seq adapters to target RNA sequences without RNA ligation. The new TGIRT-seq method enabled construction of RNA-seq libraries from RNA in RNA in 1-mL plasma samples from a healthy individual revealed RNA fragments mapping to a diverse population of protein-coding gene and long ncRNAs, which are enriched in intron and antisense sequences, as well as nearly all known classes of small ncRNAs, some of which have never before been seen in plasma. Surprisingly, many of the small ncRNA species were present as full-length transcripts, suggesting that they are protected from plasma RNases in ribonucleoprotein (RNP) complexes and/or exosomes. This TGIRT-seq method is readily adaptable for profiling of whole-cell, exosomal, and miRNAs, and for related procedures, such as HITS-CLIP and ribosome profiling. PMID:26554030

  6. Analysis of angiotensin II binding to human platelets: Differences in young and old subjects

    International Nuclear Information System (INIS)

    Siebers, M.J.; Goodfriend, T.L.; Ball, D.; Elliott, M.E.

    1990-01-01

    We examined the binding of radiolabeled angiotensin II (AII) to human platelets to characterize the apparent increase in AII receptors observed in older subjects. At 22 degrees C, the amount of radioactivity associated with platelets from older subjects increased continuously for more than 2 hours. The same amount of radioactivity was displaced by addition of unlabeled AII at 30 min and 60 min. In the presence of phenylarsine oxide, in the cold, or when labeled antagonist was the ligand, binding came to equilibrium by 30 min. High pressure liquid chromatography demonstrated that 125 I-AII was the major radioactive compound in the supernatant and platelets after incubation, but the platelets also contained radiolabeled AII fragments. Thus, some degradation accompanied interaction of AII and platelets. Phenylarsine oxide did not prevent degradation of bound AII, suggesting that degradation precedes internalization. On average, maximum binding was greater in older subjects whether platelets were incubated with 125 I-AII alone, with 125 I-AII and phenylarsine oxide to prevent internalization, or when the competitive inhibitor 125 I-sar1,ile8-AII was the radioligand. Variability of binding among subjects also increased with age. Thus, platelets bind, degrade, and internalize AII, and the three processes occur to a greater extent in platelets from some, but not all older subjects

  7. Class I and II histone deacetylase expression in human chronic periodontitis gingival tissue.

    Science.gov (United States)

    Cantley, M D; Dharmapatni, A A S S K; Algate, K; Crotti, T N; Bartold, P M; Haynes, D R

    2016-04-01

    Histone deacetylase inhibitors (HDACi) are being considered to treat chronic inflammatory diseases at low doses. Currently HDACi that are more specific are being developed to target particular HDACs; therefore, this study aimed to determine levels and distribution of class I and II HDAC in human gingival samples obtained from patients with chronic periodontitis. Gingival biopsies were obtained from patients with and without (mild inflammation, no bone loss) periodontitis. Total RNA was isolated for real-time quantitative polymerase chain reaction to determine expression of HDACs 1-10. Immunohistochemistry was used to determine protein distribution of HDACs 1, 5, 8 and 9. Factor VIII, CD3 and tartrate resistant acid phosphatase (TRAP) were detected in serial sections to identify blood vessels, lymphocytes, pre-osteoclasts and osteoclasts cells respectively. Tumour necrosis factor α (TNF-α) expression was also assessed. mRNA for HDAC 1, 5, 8 and 9 were significantly upregulated in chronic periodontitis gingival tissues compared to non-periodontitis samples (p chronic periodontitis samples (p chronic periodontitis gingival tissues. HDAC 1, 5, 8 and 9 expression was higher in gingival tissues from patients with chronic periodontitis compared to non-periodontitis samples. Results suggest that these HDACs could therefore be targeted with specific acting HDACi. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. A clinical evaluation of a bioresorbable membrane and porous hydroxyapatite in the treatment of human molar class II furcations

    Directory of Open Access Journals (Sweden)

    K Gita Malathi

    2013-01-01

    Full Text Available Background: The ultimate goal of periodontal therapy is predictable regeneration of a functional attachment apparatus destroyed as a result of periodontitis. Reconstructive procedures have been used with varying success during the past decades to accomplish this goal. Aim: To evaluate whether the use of porous hydroxyapatite alone or a bioresorbable membrane alone would enhance the clinical results in the treatment of class II furcation defects in human lower molars. Materials and Methods: Fifteen patients with chronic periodontitis, aged between 39 and 49 years, with a pair of similar bilateral class II furcation defects (classification of Hamp et al. in mandibular first molars were selected. A split-mouth design was incorporated and the selected 30 furcation defects were assigned to one of the two treatment groups, i.e., Group I treated with a bioresorbable membrane from bovine-derived collagen guided tissue regeneration membrane and Group II treated using porous hydroxyapatite bone graft material on the contralateral sides. Evaluation of clinical parameters, probing depths and attachment levels, and radiographs was done preoperatively and 6 months postoperatively. Results: Both the groups showed statistically significant mean reduction in probing depths and gain in clinical attachment levels and linear bone fill. Comparison between Group I and Group II showed insignificant difference. Conclusion: Within the limits of this study, both the treatment modalities are beneficial for the treatment of human mandibular class II furcation defects.

  9. Local angiotensin II promotes adipogenic differentiation of human adipose tissue mesenchymal stem cells through type 2 angiotensin receptor

    Directory of Open Access Journals (Sweden)

    Veronika Y. Sysoeva

    2017-12-01

    Full Text Available Obesity is often associated with high systemic and local activity of renin-angiotensin system (RAS. Mesenchymal stem cells of adipose tissue are the main source of adipocytes. The aim of this study was to clarify how local RAS could control adipose differentiation of human adipose tissue derived mesenchymal stem cells (ADSCs. We examined the distribution of angiotensin receptor expressing cells in human adipose tissue and found that type 1 and type 2 receptors are co-expressed in its stromal compartment, which is known to contain mesenchymal stem cells. To study the expression of receptors specifically in ADSCs we have isolated them from adipose tissue. Up to 99% of cultured ADSCs expressed angiotensin II (AngII receptor type 1 (AT1. Using the analysis of Ca2+ mobilization in single cells we found that only 5.2 ± 2.7% of ADSCs specifically respond to serial Ang II applications via AT1 receptor and expressed this receptor constantly. This AT1const ADSCs subpopulation exhibited increased adipose competency, which was triggered by endogenous AngII. Inhibitory and expression analyses showed that AT1const ADSCs highly co-express AngII type 2 receptor (AT2, which was responsible for increased adipose competency of this ADSC subpopulation.

  10. PPAR-δ Agonist With Mesenchymal Stem Cells Induces Type II Collagen-Producing Chondrocytes in Human Arthritic Synovial Fluid.

    Science.gov (United States)

    Heck, Bruce E; Park, Joshua J; Makani, Vishruti; Kim, Eun-Cheol; Kim, Dong Hyun

    2017-08-01

    Osteoarthritis (OA) is an inflammatory joint disease characterized by degeneration of articular cartilage within synovial joints. An estimated 27 million Americans suffer from OA, and the population is expected to reach 67 million in the United States by 2030. Thus, it is urgent to find an effective treatment for OA. Traditional OA treatments have no disease-modifying effect, while regenerative OA therapies such as autologous chondrocyte implantation show some promise. Nonetheless, current regenerative therapies do not overcome synovial inflammation that suppresses the differentiation of mesenchymal stem cells (MSCs) to chondrocytes and the expression of type II collagen, the major constituent of functional cartilage. We discovered a synergistic combination that overcame synovial inflammation to form type II collagen-producing chondrocytes. The combination consists of peroxisome proliferator-activated receptor (PPAR) δ agonist, human bone marrow (hBM)-derived MSCs, and hyaluronic acid (HA) gel. Interestingly, those individual components showed their own strong enhancing effects on chondrogenesis. GW0742, a PPAR-δ agonist, greatly enhanced MSC chondrogenesis and the expression of type II collagen and glycosaminoglycan (GAG) in hBM-MSC-derived chondrocytes. GW0742 also increased the expression of transforming growth factor β that enhances chondrogenesis and suppresses cartilage fibrillation, ossification, and inflammation. HA gel also increased MSC chondrogenesis and GAG production. However, neither GW0742 nor HA gel could enhance the formation of type II collagen-producing chondrocytes from hBM-MSCs within human OA synovial fluid. Our data demonstrated that the combination of hBM-MSCs, PPAR-δ agonist, and HA gel significantly enhanced the formation of type II collagen-producing chondrocytes within OA synovial fluid from 3 different donors. In other words, the novel combination of PPAR-δ agonist, hBM-MSCs, and HA gel can overcome synovial inflammation to form

  11. La ciencia política, ciencia noética del orden.

    Directory of Open Access Journals (Sweden)

    Felipe Cárdenas Támara.

    2010-07-01

    Full Text Available This work has the following fundamental purposes: i to respond by way of a critical review to the statements on political science's object of study made by Rodrigo Losada and Andrés Casas in their recently published book Enfoques para el análisis político. Historia, epistemología y perspectivas de la ciencia política (Approaches for Political Analysis. History, Epistemology and Perspectives of Political Science, 2008; ii to reflect on the theoretical reductionism in the conceptualization of the object of study of political science, present in some contemporary schools of thought, and, iii to suggest the need to expand our understanding of our political reality from the intellectual perspective proposed by Eric Voegelin, who argued that political science is a noetic scientific discipline centered on the study of order and the experience of order in societies and human cultures. The contribu-tion of the article refers to the reconstitution and resignification of political science as a scientific noetic discipline and to the multiple transdisciplinary fields that such a condition makes possible.

  12. Prevalence of human T-lymphotropic virus type I and type II antibody among blood donors in Eastern Saudi Arabia.

    Science.gov (United States)

    Ul-Hassan, Zahoor; Al-Bahrani, Ahmad T; Panhotra, Bodh R

    2004-10-01

    Human T-cell leukemia/lymphoma virus type I and type II (HTLV-I/II) infections can be transfusion associated, leading to tropical paraparesis, myelopathy and other neurological disorders. The aim of this study is to circumvent the risk of transmission through blood transfusion and to describe the prevalence of HTLV-I/II antibody among blood donors of Al-Hasa region and the cost effectiveness of screening blood donors. The study was conducted at the Department of Laboratory and Blood Bank, King Fahad Hospital, Al-Hofuf, Al-Hasa, Kingdom of Saudi Arabia during the period of 1997 to 2003. A total of 47426 blood donors were screened for HTLV-I/II antibody by enzyme-linked immunosorbent assay test, during the 7 years of study period. The positive samples were confirmed by western blot analysis. Overall, HTLV-I antibody positivity (confirmed by western blot) was 3/47426 (0.006%). Out of 3 donors positive for HTLV-I antibody during 1997 to 1998, 2 were expatriates (Indian) and one was native Saudi donor. Human T-cell leukemia/lymphoma virus type I antibody positivity among the native Saudi donors was 1/47426 (0.002%) (2/100000 blood donors). None of the donor were positive for HTLV-II antibody. During the last 5 consecutive years of the study period (1999-2003), none of the donor was positive for HTLV-I/II antibody. Al-Hasa region is non-endemic for HTLV-I/II virus infections. Screening of native Saudi blood donors for these viruses does not appear to be cost effective.

  13. Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro

    Science.gov (United States)

    Tamaddon, M.; Burrows, M.; Ferreira, S. A.; Dazzi, F.; Apperley, J. F.; Bradshaw, A.; Brand, D. D.; Czernuszka, J.; Gentleman, E.

    2017-03-01

    Osteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS - which was released from scaffolds quickly - significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.

  14. Roles of Saccharomyces cerevisiae DNA polymerases Polη and Polζ in response to irradiation by simulated sunlight

    Science.gov (United States)

    Kozmin, Stanislav G.; Pavlov, Youri I.; Kunkel, Thomas A.; Sage, Evelyne

    2003-01-01

    Sunlight causes lesions in DNA that if unrepaired and inaccurately replicated by DNA polymerases yield mutations that result in skin cancer in humans. Two enzymes involved in translesion synthesis (TLS) of UV-induced photolesions are DNA polymerase η (Polη) and polymerase ζ (Polζ), encoded by the RAD30A and REV3 genes, respectively. Previous studies have investigated the TLS roles of these polymerases in human and yeast cells irradiated with monochromatic, short wavelength UVC radiation (254 nm). However, less is known about cellular responses to solar radiation, which is of higher and mixed wavelengths (310–1100 nm) and produces a different spectrum of DNA lesions, including Dewar photoproducts and oxidative lesions. Here we report on the comparative cytotoxic and mutagenic effects of simulated sunlight (SSL) and UVC radiation on yeast wild-type, rad30Δ, rev3Δ and rev3Δ rad30Δ strains. The results with SSL support several previous interpretations on the roles of these two polymerases in TLS of photodimers and (6–4) photoproducts derived from studies with UVC. They further suggest that Polη participates in the non-mutagenic bypass of SSL-dependent cytosine-containing Dewar photoproducts and 8-oxoguanine, while Polζ is mainly responsible for the mutagenic bypass of all types of Dewar photoproducts. They also suggest that in the absence of Polζ, Polη contributes to UVC- and SSL-induced mutagenesis, possibly by the bypass of photodimers containing deaminated cytosine. PMID:12888515

  15. Type II collagen C2C epitope in human synovial fluid and serum after knee injury

    DEFF Research Database (Denmark)

    Kumahashi, N; Swärd, P; Larsson, S

    2015-01-01

    PURPOSE: Investigate in a cross-sectional study time-dependent changes of synovial fluid type II collagen epitope C2C concentrations after knee injury and correlate to other joint injury biomarkers. METHODS: Synovial fluid samples were aspirated between 0 days and 7 years after injury (n = 235...... = 0.403, P type II collagen (r = 0.444, P = 0.003), ARGS-aggrecan (r = 0.337, P ... with an immediate and sustained local degradation of type II collagen....

  16. A Plea for the traditional family: Situating marriage within John Paul II's realist, or personalist, perspective of human freedom1

    Science.gov (United States)

    Schumacher, Michele M.

    2014-01-01

    This article is an attempt to defend the rights of the traditional family: not simply against the redefinition of marriage, but more fundamentally against a re-conceptualization of human freedom and human rights. To this end, it contrasts what Saint John Paul II calls an individualistic understanding of freedom and a personalistic notion of the same in order to argue that human freedom is called by the Creator to be in service of, and not in opposition to, the good of the human family. From this perspective—that of the social doctrine of the Catholic Church—it argues for the harmony between natural marriage and the respect of fundamental human rights, and it presents the social dimension of marriage as fundamental with respect to the legal and social protection of the family. PMID:25473131

  17. Effect of endocrine therapy on growth of T61 human breast cancer xenografts is directly correlated to a specific down-regulation of insulin-like growth factor II (IGF-II)

    DEFF Research Database (Denmark)

    Brünner, N; Yee, D; Kern, F G

    1993-01-01

    xenograft. Growth of the T61 tumour is inhibited by treatment with E2 and TAM. Ribonuclease (RNAse) protection assays with human- and mouse-specific IGF-II antisense probes were used to study the regulation of IGF-II mRNA by E2 and TAM in the tumour. IGF-II protein expression was studied by radioimmunoassay......-IR3 resulted in inhibition of tumour growth during treatment.(ABSTRACT TRUNCATED AT 400 WORDS)...

  18. Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome

    Energy Technology Data Exchange (ETDEWEB)

    DeFreitas, E.; Hilliard, B.; Cheney, P.R.; Bell, D.S.; Kiggundu, E.; Sankey, D.; Wroblewska, Z.; Palladino, M.; Woodward, J.P.; Koprowski, H. (Wistar Inst., Philadelphia, PA (United States))

    1991-04-01

    Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but unknown etiology. The authors evaluted 30 adult and pediatric CFIDS patients from six eastern states for the presence of human T-lymphotropic virus (HTLV) types I and II by Western immunoblotting, polymerase chain reaction, and in situ hybridization of blood samples. The majority of patients were positive for HTLV antibodies by Western blotting and for HTLV-II gag sequences by polymerase chain reaction and in situ hybridization. Twenty nonexposure healthy controls were negative in all assays. These data support an association between an HTLV-II-like virus and CFIDS.

  19. Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome

    International Nuclear Information System (INIS)

    DeFreitas, E.; Hilliard, B.; Cheney, P.R.; Bell, D.S.; Kiggundu, E.; Sankey, D.; Wroblewska, Z.; Palladino, M.; Woodward, J.P.; Koprowski, H.

    1991-01-01

    Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but unknown etiology. The authors evaluted 30 adult and pediatric CFIDS patients from six eastern states for the presence of human T-lymphotropic virus (HTLV) types I and II by Western immunoblotting, polymerase chain reaction, and in situ hybridization of blood samples. The majority of patients were positive for HTLV antibodies by Western blotting and for HTLV-II gag sequences by polymerase chain reaction and in situ hybridization. Twenty nonexposure healthy controls were negative in all assays. These data support an association between an HTLV-II-like virus and CFIDS

  20. Human cytomegalovirus alters localization of MHC class II and dendrite morphology in mature Langerhans cells.

    Science.gov (United States)

    Lee, Andrew W; Hertel, Laura; Louie, Ryan K; Burster, Timo; Lacaille, Vashti; Pashine, Achal; Abate, Davide A; Mocarski, Edward S; Mellins, Elizabeth D

    2006-09-15

    Hemopoietic stem cell-derived mature Langerhans-type dendritic cells (LC) are susceptible to productive infection by human CMV (HCMV). To investigate the impact of infection on this cell type, we examined HLA-DR biosynthesis and trafficking in mature LC cultures exposed to HCMV. We found decreased surface HLA-DR levels in viral Ag-positive as well as in Ag-negative mature LC. Inhibition of HLA-DR was independent of expression of unique short US2-US11 region gene products by HCMV. Indeed, exposure to UV-inactivated virus, but not to conditioned medium from infected cells, was sufficient to reduce HLA-DR on mature LC, implicating particle binding/penetration in this effect. Reduced surface levels reflected an altered distribution of HLA-DR because total cellular HLA-DR was not diminished. Accumulation of HLA-DR was not explained by altered cathepsin S activity. Mature, peptide-loaded HLA-DR molecules were retained within cells, as assessed by the proportion of SDS-stable HLA-DR dimers. A block in egress was implicated, as endocytosis of surface HLA-DR was not increased. Immunofluorescence microscopy corroborated the intracellular retention of HLA-DR and revealed markedly fewer HLA-DR-positive dendritic projections in infected mature LC. Unexpectedly, light microscopic analyses showed a dramatic loss of the dendrites themselves and immunofluorescence revealed that cytoskeletal elements crucial for the formation and maintenance of dendrites are disrupted in viral Ag-positive cells. Consistent with these dendrite effects, HCMV-infected mature LC exhibit markedly reduced chemotaxis in response to lymphoid chemokines. Thus, HCMV impedes MHC class II molecule trafficking, dendritic projections, and migration of mature LC. These changes likely contribute to the reduced activation of CD4+ T cells by HCMV-infected mature LC.

  1. Reaction Coordinate, Free Energy, and Rate of Intramolecular Proton Transfer in Human Carbonic Anhydrase II.

    Science.gov (United States)

    Paul, Sanjib; Paul, Tanmoy Kumar; Taraphder, Srabani

    2018-03-22

    The role of structure and dynamics of an enzyme has been investigated at three different stages of its function including the chemical event it catalyzes. A one-pot computational method has been designed for each of these stages on the basis of classical and/or quantum mechanical-molecular mechanical molecular dynamics and transition path sampling simulations. For a pair of initial and final states A and B separated by a high free-energy barrier, using a two-stage selection process, several collective variables (CVs) are identified that can delineate A and B. However, these CVs are found to exhibit strong cross-coupling over the transition paths. A set of mutually orthogonal order parameters is then derived from these CVs and an optimal reaction coordinate, r, determined applying half-trajectory likelihood maximization along with a Bayesian information criterion. The transition paths are also used to project the multidimensional free energy surface and barrier crossing dynamics along r. The proposed scheme has been applied to the rate-determining intramolecular proton transfer reaction of the well-known enzyme human carbonic anhydrase II. The potential of mean force, F( r), in the absence of the chemical step is found to reproduce earlier results on the equilibrium population of two side-chain orientations of key residue His-64. Estimation of rate constants, k, from mean first passage times for the three different stages of catalysis shows that the rate-determining step of intramolecular proton transfer occurs with k ≃ 1.0 × 10 6 s -1 , in close agreement with known experimental results.

  2. Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.

    Directory of Open Access Journals (Sweden)

    Katherine J Kasper

    2014-05-01

    Full Text Available Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs as 'trademark' virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS, how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6 mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC -II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms.

  3. Proviral HIV-genome-wide and pol-gene specific Zinc Finger Nucleases: Usability for targeted HIV gene therapy

    Directory of Open Access Journals (Sweden)

    Wayengera Misaki

    2011-07-01

    Full Text Available Abstract Background Infection with HIV, which culminates in the establishment of a latent proviral reservoir, presents formidable challenges for ultimate cure. Building on the hypothesis that ex-vivo or even in-vivo abolition or disruption of HIV-gene/genome-action by target mutagenesis or excision can irreversibly abrogate HIV's innate fitness to replicate and survive, we previously identified the isoschizomeric bacteria restriction enzymes (REases AcsI and ApoI as potent cleavers of the HIV-pol gene (11 and 9 times in HIV-1 and 2, respectively. However, both enzymes, along with others found to cleave across the entire HIV-1 genome, slice (SX at palindromic sequences that are prevalent within the human genome and thereby pose the risk of host genome toxicity. A long-term goal in the field of R-M enzymatic therapeutics has thus been to generate synthetic restriction endonucleases with longer recognition sites limited in specificity to HIV. We aimed (i to assemble and construct zinc finger arrays and nucleases (ZFN with either proviral-HIV-pol gene or proviral-HIV-1 whole-genome specificity respectively, and (ii to advance a model for pre-clinically testing lentiviral vectors (LV that deliver and transduce either ZFN genotype. Methods and Results First, we computationally generated the consensus sequences of (a 114 dsDNA-binding zinc finger (Zif arrays (ZFAs or ZifHIV-pol and (b two zinc-finger nucleases (ZFNs which, unlike the AcsI and ApoI homeodomains, possess specificity to >18 base-pair sequences uniquely present within the HIV-pol gene (ZifHIV-polFN. Another 15 ZFNs targeting >18 bp sequences within the complete HIV-1 proviral genome were constructed (ZifHIV-1FN. Second, a model for constructing lentiviral vectors (LVs that deliver and transduce a diploid copy of either ZifHIV-polFN or ZifHIV-1FN chimeric genes (termed LV- 2xZifHIV-polFN and LV- 2xZifHIV-1FN, respectively is proposed. Third, two preclinical models for controlled testing of

  4. Interdisciplinary Evaluation of Broadly-Reactive HLA Class II Restricted Epitopes Eliciting HIV-Specific CD4+T Cell Responses

    DEFF Research Database (Denmark)

    Buggert, M.; Norström, M.; Lundegaard, Claus

    2011-01-01

    , the functional and immunodominant discrepancies of CD4+ T cell responses targeting promiscuous MHC II restricted HIV epitopes remains poorly defined. Thus, utilization of interdisciplinary approaches might aid revealing broadly- reactive peptides eliciting CD4 + T cell responses. Methods: We utilized the novel...... bioinformatic prediction program NetMHCIIpan to select 64 optimized MHC II restricted epitopes located in the HIV Gag, Pol, Env, Nef and Tat regions. The epitopes were selected to cover the global diversity of the virus (multiple subtypes) and the human immune system(diverse MHC II types). Optimized...

  5. Changes in distribution of hepatic blood flow induced by intra-arterial infusion of angiotensin II in human hepatic cancer

    International Nuclear Information System (INIS)

    Sasaki, Y.; Imaoka, S.; Hasegawa, Y.

    1985-01-01

    Changes in the distribution of the hepatic blood flow induced by intra-arterial infusion of angiotensin II (AT-II) were studied in human hepatic cancers using extremely short-lived radioisotope (RI) (krypton 81 m [/sup 81m/Kr]; half-life, 13 seconds). After the start of continuous infusion of AT-II, the radioactivity of the tumor showed about a two-fold increase, whereas that of the nontumor region decreased to about one half as much as the level before the infusion. Consequently, the mean ratio of the arterial blood flow in the tumor region to that in the nontumor region (T/N ratio) increased to 3.30 (P less than 0.001). The T/N ratio showed a peak before the peripheral blood pressure reached the maximum, and thereafter tended to decrease. Intra-arterial infusion of AT-II raised the T/N ratio more obviously than did intravenous infusion of the drug, with less rise in the peripheral blood pressure. It is believed that intra-arterial infusion chemotherapy with local use of AT-II enables better accessibility of chemotherapeutic drugs to tumors

  6. Nitric oxide and bcl-2 mediated the apoptosis induced by nickel(II) in human T hybridoma cells

    International Nuclear Information System (INIS)

    Guan Fuqin; Zhang Dongmei; Wang Xinchang; Chen Junhui

    2007-01-01

    Although effects of nickel(II) on the immune system have long been recognized, little is known about the effects of nickel(II) on the induction of apoptosis and related signaling events in T cells. In the present study, we investigated the roles and signaling pathways of nickel(II) in the induction of apoptosis in a human T cell line jurkat. The results showed that the cytotoxic effects of Ni involved significant morphological changes and chromosomal condensation (Hoechst 33258 staining). Analyses of hypodiploid cells and FITC-Annexin V and PI double staining showed significant increase of apoptosis in jurkat cells 6, 12 and 24 h after nickel(II) treatment. Flow cytometry analysis also revealed that the loss of mitochondrial membrane potential (MMP) occurred concomitantly with the onset of NiCl 2 -induced apoptosis. Induction of apoptotic cell death by nickel was mediated by reduction of bcl-2 expression. Furthermore, nickel stimulated the generation of nitric oxide (NO). These results suggest that nickel(II) chloride induces jurkat cells apoptosis via nitric oxide generation, mitochondrial depolarization and bcl-2 suppression

  7. {sup 18}F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Chunjing; Mi, Baoming; Wan, Weixing [Affiliated Hospital of Jiangnan University (Wuxi No. 4 People' s Hospital), Department of Nuclear Medicine, Wuxi (China); Pan, Donghui; Xu, Yuping; Yang, Min [Jiangsu Institute of Nuclear Medicine, Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Wuxi (China); Lang, Lixin; Niu, Gang; Chen, Xiaoyuan [National Institutes of Health, Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States)

    2015-12-15

    We report the biodistribution and radiation dosimetry of an integrin α{sub v}β{sub 3} specific PET tracer {sup 18}F-AlF-NOTA-E[PEG{sub 4}-c(RGDfk)]{sub 2} (denoted as {sup 18}F-Alfatide II). We also assessed the value of {sup 18}F-Alfatide II in patients with brain metastases. A series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of {sup 18}F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with {sup 18}F-FDG (5.55 MBq/kg) and {sup 18}F-Alfatide II. Injection of {sup 18}F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. {sup 18}F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by {sup 18}F-Alfatide II PET, while only ten lesions were visualized by {sup 18}F-FDG, and 13 by CT. F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that {sup 18}F-Alfatide II is feasible for human studies. {sup 18}F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis. (orig.)

  8. La política focalizada en el programa de vacunación contra el Virus del Papiloma Humano en México: aspectos éticos Na política centrada no programa de vacinação contra o HPV no México: Suas dilema ético The policy focused on the HPV vaccination program against Human Papilloma Virus in Mexico: ethics aspects

    Directory of Open Access Journals (Sweden)

    Kirvis Janneth Torres-Poveda

    2011-06-01

    Full Text Available Se plantea un análisis ético de aspectos relacionados con la introducción de nuevas vacunas contra el Virus del Papiloma Humano en México, cuya política de distribución atiende a la equidad más que a la igualdad y tiene como ejes fundamentales abarcar a las personas más vulnerables y al costo más bajo posible, es decir, atiende a los principios de justicia distributiva. El esquema inicial de vacunación contra este virus en México se ha focalizado a la población femenina más marginada, la cual se concentra en las mujeres indígenas. Las estrategias de distribución de nuevas vacunas deberán tomar en consideración las características específicas en que se desenvuelven estos grupos y analizar las implicaciones éticas que tales medidas conllevan. Sin ello, una política de salud pública podría aumentar las desigualdades en materia de salud.O propósito foi fazer uma análise ética das questões relacionadas com a introdução de novas vacinas contra o Papilomavírus Humano, no México, cuja política de distribuição serve apenas para a equidade mais do que para a igualdade e tem como eixos fundamentais abrangir os mais vulneráveis e os menores custos possíveis, isto é, servindo aos princípios de justiça distributiva. O regime inicial da vacinação contra esse vírus no México tem sido focado na população feminina mais marginalizada, que incide sobre as mulheres indígenas. As estratégias de distribuição de novas vacinas devem tomar em consideração as características específicas que desses grupos e analisar as implicações éticas que tais medidas implicam, sem isso a política de saúde pública poderia aumentar as desigualdades na saúde.This article raises an ethical analysis of issues related to the introduction of new vaccines against Human Papillomavirus in Mexico, whose distribution policy attend to equity more than equality, and has as fundamental axes to cover the most vulnerable people and the lowest

  9. Relative cytotoxicity of complexes of platinum(II and palladium(II against pure cell culture Paramecium caudatum and human cell lines A431 and HaCaT

    Directory of Open Access Journals (Sweden)

    Aleksei Vladimirovich Eremin

    2018-04-01

    Full Text Available The results of cytotoxicity cisplatin-like complexes of platinum(II and palladium(II are presented. The cytotoxicity was researched by method of  biotesting with Paramecium caudatum and by MTT-assay with human cells: epidermoid carcimoma A431 and minimal transformed aneuploid keratinocytes HaCaT. Cytotoxicity of complexes toward protists is high, however, comparatively HaCaT are more sensitive than A431. Furthemore, cytotoxicity of palladium(II complexes is higher than the analogues with platinum(II.

  10. Human T-cell Lymphotropic Virus types I and II (HTLV-I/II in French Guiana: clinical and molecular epidemiology

    Directory of Open Access Journals (Sweden)

    Kazanji Mirdad

    2003-01-01

    Full Text Available We review here the epidemiological studies performed by our group on human retrovirus HTLV-I and HTLV-II infections and the associated diseases in French Guiana since 1984. French Guiana is an overseas French administrative district located between Brazil and Surinam. Its population is characterized by a large variety of ethnic groups, including several populations of African origin and various populations of Amerindian origin. Several epidemiological studies of large samples of pregnant women and in remote villages showed that HTLV-I is highly endemic in this area but is restricted to groups of African origin, especially the Noir-Marrons. In this endemic population, the results of segregation analysis in a genetic epidemiological study were consistent with the presence of a dominant major gene predisposing to HTLV-I infection, especially in children. In contrast, HTLV-II infection appears to be rare in French Guiana, having been found in only a few individuals of Brazilian origin. From a molecular point of view, the HTLV-I strains present in the Noir-Marrons, Creoles and Amerindians appear to originate from Africa, as they belong to the large cosmopolitan molecular subtype A.

  11. Advanced 3D Human Simulation Components with Thermal/Haptic Feedback and Tissue Deformation, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In integrating the following three significant components for its research/research and development (R/R&D) effort, the power of this candidate Phase II project...

  12. Os direitos humanos e a política internacional

    Directory of Open Access Journals (Sweden)

    Rossana Rocha Reis

    2006-11-01

    Full Text Available O artigo trata da questão do crescente reconhecimento internacional dos direitos humanos desde o fim da II Guerra Mundial e discute os efeitos desse processo sobre a política internacional. De modo geral os argumentos sobre o papel dos direitos humanos na política internacional dividem-se entre os que acham que eles não passam de retórica para encobrir interesses particulares, e os que enxergam na sua afirmação um potencial transformador da ordem internacional. No contexto atual,em que se discute a adoção de mecanismos coercitivos mais fortes para a proteção dos direitos humanos, como as intervenções humanitárias, por exemplo, essa discussão torna-se mais complexa e mais urgente.

  13. Human urotensin II in internal mammary and radial arteries of patients undergoing coronary surgery

    DEFF Research Database (Denmark)

    Chen, Zhi-Wu; Yang, Qin; Huang, Yu

    2009-01-01

    (max):20.4+/-4.8%, p7.1%). The relaxation was abolished by endothelium denudation...... and by indomethacin, oxadiazoloquinoxalinone or N(omega)-nitro-L-arginine, oxyhemoglobin, and Ca2+-activated K+ channel (K(Ca)) blockers. Urotensin receptor mRNA was detected in both arteries. CONCLUSIONS: hU-II is an important spasmogen in arterial grafts with receptors expressed in IMA and RA. hU-II elicits...

  14. Nature of the Nucleosomal Barrier to RNA Polymerase II | Center for Cancer Research

    Science.gov (United States)

    In the cell, RNA polymerase II (pol II) efficiently transcribes DNA packaged into nucleosomes, but in vitro encounters with the nucleosomes induce catalytic inactivation (arrest) of the pol II core enzyme. To determine potential mechanisms making nucleosomes transparent to transcription in vivo, we analyzed the nature of the nucleosome-induced arrest. We found that the arrests

  15. Urotensin-II receptor is over-expressed in colon cancer cell lines and in colon carcinoma in humans.

    Science.gov (United States)

    Federico, Alessandro; Zappavigna, Silvia; Romano, Marco; Grieco, Paolo; Luce, Amalia; Marra, Monica; Gravina, Antonietta Gerarda; Stiuso, Paola; D'Armiento, Francesco Paolo; Vitale, Giovanni; Tuccillo, Concetta; Novellino, Ettore; Loguercio, Carmela; Caraglia, Michele

    2014-01-01

    Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown. We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells. Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion. UTR appears to be involved in the regulation of colon cancer cell invasion and motility. These data suggest that UTR-related pathway may play a role in colon carcinogenesis and that UTR may function as a target for therapeutic intervention in colon cancer. © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

  16. Rapid radioimmunoassay of human apolipoproteins C-II and C-III

    Energy Technology Data Exchange (ETDEWEB)

    Gustafson, S; Oestlund-Lindqvist, A M; Vessby, B [Uppsala Univ. (Sweden)

    1984-06-01

    Apolipoprotein (apo) C-II is an activator of lipoprotein lipase, while apo C-III has the ability to inhibit apo C-II activated lipolysis. In order to study further the relationship between lipoprotein lipase mediated hydrolysis and the serum concentrations of apo C-II and apo C-III radioimmunoassays for these apolipoproteins have been developed. Formalin-treated Staphylococcus aureus Cowan I was used for immunoprecipitation and were shown to give rapid uptake of immune complexes that could easily be harvested by centrifugation. The assays were shown to be sensitive (10 ..mu..g/1), specific, precise (inter- and intra-assay coefficients of variation below 10%), rapid (completed in less than 6 h) and simple to perform. Delipidation of serum and lipoproteins had no effect on the results, indicating that the immunologically active sites of apo C-II and apo C-III are exposed to the aqueous environment under assay conditions. Serum apo C-II and apo C-III levels of normolipidaemic subjects were approximately 25 mg/1 and 110 mg/1, respectively. Highly significant positive correlations were found between VLDL apo C-II and VLDL apo C-III, respectively, and VLDL triglycerides, VLDL cholesterol and total serum TG. There was also a highly significant correlation between the HDL cholesterol concentration and the HDL apo C-III concentration.

  17. Cellular responses induced by Cu(II quinolinonato complexes in human tumor and hepatic cells

    Directory of Open Access Journals (Sweden)

    Trávníček Zdeněk

    2012-12-01

    Full Text Available Abstract Background Inspired by the unprecedented historical success of cisplatin, one of the most important research directions in bioinorganic and medicinal chemistry is dedicated to the development of new anticancer compounds with the potential to surpass it in antitumor activity, while having lower unwanted side-effects. Therefore, a series of copper(II mixed-ligand complexes of the type [Cu(qui(L]Y · xH2O (1–6, where Hqui = 2-phenyl-3-hydroxy-4(1H-quinolinone, Y = NO3 (1, 3, 5 or BF4 (2, 4, 6, and L = 1,10-phenanthroline (phen (1, 2, 5-methyl-1,10-phenanthroline (mphen (3, 4 and bathophenanthroline (bphen (5, 6, was studied for their in vitro cytotoxicity against several human cancer cell lines (A549 lung carcinoma, HeLa cervix epitheloid carcinoma, G361 melanoma cells, A2780 ovarian carcinoma, A2780cis cisplatin-resistant ovarian carcinoma, LNCaP androgen-sensitive prostate adenocarcinoma and THP-1 monocytic leukemia. Results The tested complexes displayed a stronger cytotoxic effect against all the cancer cells as compared to cisplatin. The highest cytotoxicity was found for the complexes 4 (IC50 = 0.36 ± 0.05 μM and 0.56 ± 0.15 μM, 5 (IC50 = 0.66 ± 0.07 μM and 0.73 ± 0.08 μM and 6 (IC50 = 0.57 ± 0.11 μM and 0.70 ± 0.20 μM against A2780, and A2780cis respectively, as compared with the values of 12.0 ± 0.8 μM and 27.0 ± 4.6 μM determined for cisplatin. Moreover, the tested complexes were much less cytotoxic to primary human hepatocytes than to the cancer cells. The complexes 5 and 6 exhibited significantly high ability to modulate secretion of the pro-inflammatory cytokines TNF-α (2873 ± 238 pg/mL and 3284 ± 139 pg/mL for 5, and 6 respectively and IL-1β (1177 ± 128 pg/mL and 1087 ± 101 pg/mL for 5, and 6 respectively tested on the lipopolysaccharide (LPS-stimulated THP-1 cells as compared with the values of 1173

  18. The Cu(II) affinity of the N-terminus of human copper transporter CTR1: Comparison of human and mouse sequences.

    Science.gov (United States)

    Bossak, Karolina; Drew, Simon C; Stefaniak, Ewelina; Płonka, Dawid; Bonna, Arkadiusz; Bal, Wojciech

    2018-05-01

    Copper Transporter 1 (CTR1) is a homotrimeric membrane protein providing the main route of copper transport into eukaryotic cells from the extracellular milieu. Its N-terminal extracellular domain, rich in His and Met residues, is considered responsible for directing copper into the transmembrane channel. Most of vertebrate CTR1 proteins contain the His residue in position three from N-terminus, creating a well-known Amino Terminal Cu(II)- and Ni(II)-Binding (ATCUN) site. CTR1 from humans, primates and many other species contains the Met-Asp-His (MDH) sequence, while some rodents including mouse have the Met-Asn-His (MNH) N-terminal sequence. CTR1 is thought to collect Cu(II) ions from blood copper transport proteins, including albumin, but previous reports indicated that the affinity of N-terminal peptide/domain of CTR1 is significantly lower than that of albumin, casting serious doubt on this aspect of CTR1 function. Using potentiometry and spectroscopic techniques we demonstrated that MDH-amide, a tripeptide model of human CTR1 N-terminus, binds Cu(II) with K of 1.3 × 10 13  M -1 at pH 7.4, ~13 times stronger than Human Serum Albumin (HSA), and MNH-amide is even stronger, K of 3.2 × 10 14  M -1 at pH 7.4. These results indicate that the N-terminus of CTR1 may serve as intermediate binding site during Cu(II) transfer from blood copper carriers to the transporter. MDH-amide, but not MNH-amide also forms a low abundance complex with non-ATCUN coordination involving the Met amine, His imidazole and Asp carboxylate. This species might assist Cu(II) relay down the peptide chain or its reduction to Cu(I), both steps necessary for the CTR1 function. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Can intradermal administration of angiotensin II influence human heat loss responses during whole body heat stress?

    Science.gov (United States)

    Fujii, Naoto; Meade, Robert D; Paull, Gabrielle; McGinn, Ryan; Foudil-bey, Imane; Akbari, Pegah; Kenny, Glen P

    2015-05-01

    It is unclear if angiotensin II, which can increase the production of reactive oxygen species (oxidative stress), modulates heat loss responses of cutaneous blood flow and sweating. We tested the hypothesis that angiotensin II-induced increases in oxidative stress impair cutaneous perfusion and sweating during rest and exercise in the heat. Eleven young (24 ± 4 yr) healthy adults performed two 30-min cycling bouts at a fixed rate of metabolic heat production (400 W) in the heat (35°C). The first and second exercises were followed by a 20- and 40-min recovery. Four microdialysis fibers were placed in the forearm skin for continuous administration of either: 1) lactated Ringer (control), 2) 10 μM angiotensin II, 3) 10 mM ascorbate (an antioxidant), or 4) a combination of 10 μM angiotensin II + 10 mM ascorbate. Cutaneous vascular conductance (CVC; laser-Doppler perfusion units/mean arterial pressure) and sweating (ventilated capsule) were evaluated at each skin site. Compared with control, angiotensin II reduced both CVC and sweating at baseline resting and during each recovery in the heat (all P 0.05). When ascorbate was coinfused with angiotensin II, the effect of angiotensin II on sweating was abolished (all P > 0.05); however, its effect on CVC at baseline resting and during each recovery remained intact (all P stress, while it impairs sweating through increasing oxidative stress during exposure to an ambient heat stress before and following exercise. Copyright © 2015 the American Physiological Society.

  20. Identification of sequences in herpes simplex virus type 1 ICP22 that influence RNA polymerase II modification and viral late gene expression.

    Science.gov (United States)

    Bastian, Thomas W; Rice, Stephen A

    2009-01-01

    Previous studies have shown that the herpes simplex virus type 1 (HSV-1) immediate-early protein ICP22 alters the phosphorylation of the host cell RNA polymerase II (Pol II) during viral infection. In this study, we have engineered several ICP22 plasmid and virus mutants in order to map the ICP22 sequences that are involved in this function. We identify a region in the C-terminal half of ICP22 (residues 240 to 340) that is critical for Pol II modification and further show that the N-terminal half of the protein (residues 1 to 239) is not required. However, immunofluorescence analysis indicates that the N-terminal half of ICP22 is needed for its localization to nuclear body structures. These results demonstrate that ICP22's effects on Pol II do not require that it accumulate in nuclear bodies. As ICP22 is known to enhance viral late gene expression during infection of certain cultured cells, including human embryonic lung (HEL) cells, we used our engineered viral mutants to map this function of ICP22. It was found that mutations in both the N- and C-terminal halves of ICP22 result in similar defects in viral late gene expression and growth in HEL cells, despite having distinctly different effects on Pol II. Thus, our results genetically uncouple ICP22's effects on Pol II from its effects on viral late gene expression. This suggests that these two functions of ICP22 may be due to distinct activities of the protein.

  1. CCR2 and CXCR3 agonistic chemokines are differently expressed and regulated in human alveolar epithelial cells type II

    Directory of Open Access Journals (Sweden)

    Prasse Antje

    2005-07-01

    Full Text Available Abstract The attraction of leukocytes from circulation to inflamed lungs depends on the activation of both the leukocytes and the resident cells within the lung. In this study we determined gene expression and secretion patterns for monocyte chemoattractant protein-1 (MCP-1/CCL2 and T-cell specific CXCR3 agonistic chemokines (Mig/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11 in TNF-α-, IFN-γ-, and IL-1β-stimulated human alveolar epithelial cells type II (AEC-II. AEC-II constitutively expressed high level of CCL2 mRNA in vitro and in situ , and released CCL2 protein in vitro . Treatment of AEC-II with proinflammatory cytokines up-regulated both CCL2 mRNA expression and release of immunoreactive CCL2, whereas IFN-γ had no effect on CCL2 release. In contrast, CXCR3 agonistic chemokines were not detected in freshly isolated AEC-II or in non-stimulated epithelial like cell line A549. IFN-γ, alone or in combination with IL-1β and TNF-α resulted in an increase in CXCL10, CXCL11, and CXCL9 mRNA expression and generation of CXCL10 protein by AEC-II or A549 cells. CXCL10 gene expression and secretion were induced in dose-dependent manner after cytokine-stimulation of AEC-II with an order of potency IFN-γ>>IL-1β ≥ TNF-α. Additionally, we localized the CCL2 and CXCL10 mRNAs in human lung tissue explants by in situ hybridization, and demonstrated the selective effects of cytokines and dexamethasone on CCL2 and CXCL10 expression. These data suggest that the regulation of the CCL2 and CXCL10 expression exhibit significant differences in their mechanisms, and also demonstrate that the alveolar epithelium contributes to the cytokine milieu of the lung, with the ability to respond to locally generated cytokines and to produce potent mediators of the local inflammatory response.

  2. Spectroscopic and molecular docking studies on the interaction of human serum albumin with copper(II) complexes

    Science.gov (United States)

    Guhathakurta, Bhargab; Pradhan, Ankur Bikash; Das, Suman; Bandyopadhyay, Nirmalya; Lu, Liping; Zhu, Miaoli; Naskar, Jnan Prakash

    2017-02-01

    Two osazone based ligands, butane-2,3-dione bis(2‧-pyridylhydrazone) (BDBPH) and hexane-3,4-dione bis(2‧-pyridylhydrazone) (HDBPH), were synthesized out of the 2:1 M Schiff base condensation of 2-hydrazino pyridine respectively with 2,3-butanedione and 3,4-hexanedione. The X-ray crystal structures of both the ligands have been determined. The copper(II) complex of HDBPH has also been synthesized and structurally characterized. HDBPH and its copper(II) complex have thoroughly been characterized through various spectroscopic and analytical techniques. The X-ray crystal structure of the copper complex of HDBPH shows that it is a monomeric Cu(II) complex having 'N4O2' co-ordination chromophore. Interaction of human serum albumin (HSA) with these ligands and their monomeric copper(II) complexes have been studied by various spectroscopic means. The experimental findings show that the ligands as well as their copper complexes are good HSA binders. Molecular docking investigations have also been done to unravel the mode of binding of the species with HSA.

  3. The dormant and the fully competent oocyte: comparing the transcriptome of human oocytes from primordial follicles and in metaphase II

    DEFF Research Database (Denmark)

    Grøndahl, Marie Louise; Borup, Rehannah; Vikeså, Jonas

    2013-01-01

    Oocytes become enclosed in primordial follicles during fetal life and remain dormant there until activation followed by growth and meiotic resumption. Current knowledge about the molecular pathways involved in oogenesis is incomplete. This study identifies the specific transcriptome of the human...... oocyte in the quiescent state and at the pinnacle of maturity at ovulation. In silico bioinformatic comparisons were made between the transcriptome of human oocytes from dormant primordial follicles and that of human metaphase II (MII) oocytes and granulosa cells and unique gene expression profiles were...... identified as well as functional and pathway enrichments associated with the oocytes from the two developmental hallmarks. A total of 729 genes were highly enriched in oocytes from primodial follicles and 1456 genes were highly enriched in MII oocytes (>10-fold, P...

  4. Human umbilical cord mesenchymal stromal cells suppress MHC class II expression on rat vascular endothelium and prolong survival time of cardiac allograft

    Science.gov (United States)

    Qiu, Ying; Yun, Mark M; Han, Xia; Zhao, Ruidong; Zhou, Erxia; Yun, Sheng

    2014-01-01

    Background: Human umbilical cord mesenchymal stromal cells (UC-MSCs) have low immunogenicity and immune regulation. To investigate immunomodulatory effects of human UC-MSCs on MHC class II expression and allograft, we transplanted heart of transgenic rats with MHC class II expression on vascular endothelium. Methods: UC-MSCs were obtained from human umbilical cords and confirmed with flow cytometry analysis. Transgenic rat line was established using the construct of human MHC class II transactivator gene (CIITA) under mouse ICAM-2 promoter control. The induced MHC class II expression on transgenic rat vascular endothelial cells (VECs) was assessed with immunohistological staining. And the survival time of cardiac allograft was compared between the recipients with and without UC-MSC transfusion. Results: Flow cytometry confirmed that the human UC-MSCs were positive for CD29, CD44, CD73, CD90, CD105, CD271, and negative for CD34 and HLA-DR. Repeated infusion of human UC-MSCs reduced MHC class II expression on vascular endothelia of transplanted hearts, and increased survival time of allograft. The UC-MSCs increased regulatory cytokines IL10, transforming growth factor (TGF)-β1 and suppressed proinflammatory cytokines IL2 and IFN-γ in vivo. The UC-MSC culture supernatant had similar effects on cytokine expression, and decreased lymphocyte proliferation in vitro. Conclusions: Repeated transfusion of the human UC-MSCs reduced MHC class II expression on vascular endothelia and prolonged the survival time of rat cardiac allograft. PMID:25126177

  5. Unidad 4: Crear Polígonos

    OpenAIRE

    Gómez Trigueros, Isabel María

    2015-01-01

    En esta unidad aprenderéis a crear vuestros propios polígonos con Google Earth para delimitar un área geográfica. Podréis modificar el tamaño de los polígonos, el color del área y su perímetro, incluso elaborar polígonos en 3D para superponer distintas variables sobre un paisaje concreto.

  6. Política Nacional de Humanização e formação dos profissionais de saúde: revisão integrativa Política Nacional de Humanización y formación de los profesionales de salud: revisión integrativa National Policy of Humanization and education of health care professionals: integrative review

    Directory of Open Access Journals (Sweden)

    Guilherme Correa Barbosa

    2013-02-01

    Full Text Available A Política Nacional de Humanização tem como objetivo provocar inovações na produção de saúde, gestão e no cuidado, com ênfase na educação permanente dos trabalhadores do Sistema Único de Saúde e na formação dos acadêmicos da área de saúde. Buscou-se conhecer, através de uma revisão integrativa, a produção científica sobre a Política Nacional de Humanização e a educação de trabalhadores e alunos da área da saúde, no período de 2002 a 2010. Dez artigos foram analisados na vertente temática e emergiram três eixos: humanização e o cuidado aos usuários, humanização e o processo de trabalho, humanização e a formação. Os artigos apontam a necessidade de superação da concepção biologicista e valorização dos aspectos culturais dos usuários. O processo de trabalho é marcado pela desvalorização dos trabalhadores e por usuários destituídos de seus direitos. A formação dos profissionais de saúde está pautada em serviços de saúde em que prevalece a padronização de condutas o que dificulta atitudes inovadoras.La Política Nacional de Humanización tiene como objetivo provocar innovaciones en la producción de salud, en la gerencia y en el cuidado con énfasis en la educación permanente de los trabajadores del Sistema Único de Salud y en la formación de los académicos del área de salud. En este estudio se procuró conocer, a través de una revisión integrativa, la producción científica sobre la Política Nacional de Humanización y la educación, en el período de 2002 a 2010. Diez artículos fueron analizados en un enfoque temático a través de tres ejes: humanización y atención a los usuarios, humanización y el proceso de trabajo, y humanización y formación. Los artículos apuntan a la necesidad de superar la concepción biologicista, valorando los aspectos culturales de los usuarios. El proceso de trabajo se caracteriza por la devaluación de los trabajadores y por usuarios privados

  7. Characterization of casein kinase II in human colonic carcinomas after heterotransplantation into nude mice

    DEFF Research Database (Denmark)

    Seitz, G; Münstermann, U; Schneider, H R

    1989-01-01

    Casein kinase II (CKII) activity in colorectal tumours was compared before and after heterotransplantation onto nude mice. The test revealed that the enzyme activity was about two-fold enhanced in the tumours isolated from the nude mice when compared to the respective primary tumours from which...

  8. Effect of Collagen Type I or Type II on Chondrogenesis by Cultured Human Articular Chondrocytes

    NARCIS (Netherlands)

    Rutgers, M.; Saris, Daniël B.F.; Vonk, L.A.; van Rijen, M.H.P.; Akrum, V.; Langeveld, D.; van Boxtel, A.; Dhert, W.J.A.; Creemers, L.B.

    2013-01-01

    Introduction: Current cartilage repair procedures using autologous chondrocytes rely on a variety of carriers for implantation. Collagen types I and II are frequently used and valuable properties of both were shown earlier in vitro, although a preference for either was not demonstrated. Recently,

  9. Pulmonary function testing in HTLV-I and HTLV-II infected humans: a cohort study

    Directory of Open Access Journals (Sweden)

    Garratty George

    2003-07-01

    Full Text Available Abstract Background HTLV-I infection has been linked to lung pathology and HTLV-II has been associated with an increased incidence of pneumonia and acute bronchitis. However it is unknown whether HTLV-I or -II infection alters pulmonary function. Methods We performed pulmonary function testing on HTLV-I, HTLV-II and HTLV seronegative subjects from the HTLV outcomes study (HOST, including vital capacity (VC, forced expiratory volume in one second (FEV1, and diffusing lung capacity for carbon monoxide (DLCO corrected for hemoglobin and lung volume. Multivariable analysis adjusted for differences in age, gender, race/ethnicity, height and smoking history. Results Mean (standard deviation pulmonary function values among the 257 subjects were as follows: FVC = 3.74 (0.89 L, FEV1 = 2.93 (0.67 L, DLCOcorr = 23.82 (5.89 ml/min/mmHg, alveolar ventilation (VA = 5.25 (1.20 L and DLCOcorr/VA = 4.54 (0.87 ml/min/mmHg/L. There were no differences in FVC, FEV1 and DLCOcorr/VA by HTLV status. For DLCOcorr, HTLV-I and HTLV-II subjects had slightly lower values than seronegatives, but neither difference was statistically significant after adjustment for confounding. Conclusions There was no difference in measured pulmonary function and diffusing capacity in generally healthy HTLV-I and HTLV-II subjects compared to seronegatives. These results suggest that previously described HTLV-associated abnormalities in bronchoalveolar cells and fluid may not affect pulmonary function.

  10. Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers

    OpenAIRE

    Day, Cheryl L.; Seth, Nilufer P.; Lucas, Michaela; Appel, Heiner; Gauthier, Laurent; Lauer, Georg M.; Robbins, Gregory K.; Szczepiorkowski, Zbigniew M.; Casson, Deborah R.; Chung, Raymond T.; Bell, Shannon; Harcourt, Gillian; Walker, Bruce D.; Klenerman, Paul; Wucherpfennig, Kai W.

    2003-01-01

    Containment of hepatitis C virus (HCV) and other chronic human viral infections is associated with persistence of virus-specific CD4 T cells, but ex vivo characterization of circulating CD4 T cells has not been achieved. To further define the phenotype and function of these cells, we developed a novel approach for the generation of tetrameric forms of MHC class II/peptide complexes that is based on the cellular peptide-exchange mechanism. HLA-DR molecules were expressed as precursors with a c...

  11. Sangres políticas

    Directory of Open Access Journals (Sweden)

    Gabriel Gatti

    2018-03-01

    Full Text Available Trabajamos en las tensiones entre dos continentes en permanente disputa: “sangre” y “política”, “realidad” y “dispositivo”, “naturaleza” y “cultura”. Son viejos asuntos, y viejas tensiones, pero que no dejan de actualizarse y que ahora se manifiestan por doquier en cuestiones como la biometría, los mapas genéticos, la identificación de desaparecidos, las políticas de la identidad indígena o de género o de menores o de drogas, la gestación subrogada o la gestión de la marginalidad. Los diez textos recogidos en este número especial discuten desde una mirada interdisciplinaria sobre la presencia de la sangre —en sus distintas declinaciones— en la definición contemporánea de lo que entendemos por identidad, derechos humanos o ciudadanía.

  12. N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2 locus: An animal model for human carbonic anhydrase II deficiency syndrome

    International Nuclear Information System (INIS)

    Lewis, S.E.; Barnett, L.B.; Erickson, R.P.; Venta, P.J.; Tashian, R.E.

    1988-01-01

    Electrophoretic screening of (C57BL/6J x DBA/2J)F 1 progeny of male mice treated with N-ethyl-N-nitrosourea revealed a mouse that lacked the paternal carbonic anhydrase II (Ca II). Breeding tests showed that this trait was heritable and due to a null mutation at the Car-2 locus on chromosome 3. Like humans with the same inherited enzyme defect, animals homozygous for the new null allele are runted and have renal tubular acidosis. However, the prominent osteopetrosis found in humans with CA II deficiency could be detected even in very old homozygous null mice. A molecular analysis of the deficient mice shows that the mutant gene is not deleted and is transcribed. The CA II protein, which is normally expressed in most tissues, could not be detected by immunodiffusion analysis in any tissues of the CA II-deficient mice, suggesting a nonsense or a missense mutation at the Car-2 locus

  13. Drugs associated with teratogenic mechanisms. Part II : a literature review of the evidence on human risks

    NARCIS (Netherlands)

    van Gelder, Marleen M. H. J.; de Jong-van den Berg, Lolkje T. W.; Roeleveld, Nel

    What is the current state of knowledge on the human risks of drugs suspected to be associated with teratogenic mechanisms? Evidence for the presence or absence of human risks of birth defects is scarce or non-existent for the majority of drugs associated with teratogenic mechanisms. Medical drugs

  14. Drugs associated with teratogenic mechanisms. Part II: a literature review of the evidence on human risks

    NARCIS (Netherlands)

    Gelder, M.M.H.J. van; Jong-van den Berg, L.T. de; Roeleveld, N.

    2014-01-01

    STUDY QUESTION: What is the current state of knowledge on the human risks of drugs suspected to be associated with teratogenic mechanisms? SUMMARY ANSWER: Evidence for the presence or absence of human risks of birth defects is scarce or non-existent for the majority of drugs associated with

  15. Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22

    International Nuclear Information System (INIS)

    Tsai-Pflugfelder, M.; Liu, L.F.; Liu, A.A.; Tewey, K.M.; Whang-Peng, J.; Knutsen, T.; Huebner, K.; Croce, C.M.; Wang, J.C.

    1988-01-01

    Two overlapping cDNA clones encoding human DNA topoisomerase II were identified by two independent methods. In one, a human cDNA library in phage λ was screened by hybridization with a mixed oligonucleotide probe encoding a stretch of seven amino acids found in yeast and Drosophila DNA topoisomerase II; in the other, a different human cDNA library in a λgt11 expression vector was screened for the expression of antigenic determinants that are recognized by rabbit antibodies specific to human DNA topoisomerase II. The entire coding sequences of the human DNA topoisomerase II gene were determined from these and several additional clones, identified through the use of the cloned human TOP2 gene sequences as probes. Hybridization between the cloned sequences and mRNA and genomic DNA indicates that the human enzyme is encoded by a single-copy gene. The location of the gene was mapped to chromosome 17q21-22 by in situ hybridization of a cloned fragment to metaphase chromosomes and by hybridization analysis with a panel of mouse-human hybrid cell lines, each retaining a subset of human chromosomes

  16. The Influence of Class II Division 2 Malocclusions on the Harmony of the Human Face Profile.

    Science.gov (United States)

    Perović, Tatjana

    2017-11-24

    BACKGROUND Persons with class II division 2 malocclusion are characterized by a very specific dento-skeletal and soft-tissue profile (a profile in which a protruding nose and chin, retruding lips, concave and shortened lower third of the face, and gummy smile are dominant), which is the opposite of the currently modern profiles (convex profile of protruding lips and small chin). The aim of this research was to determine the differences in parameters of harmonies of facial profiles between persons with class II division 2 malocclusions and class I, and to establish the significance of those differences. MATERIAL AND METHODS For this study, 50 patients with class II division 2 malocclusions and 50 patients with class I were selected; profile photos were recorded and a photometric analysis was done: a type of profile according to Schwarz, the shape of a nose, the prominence of chin, biometrical field, the position of lips in relation to the tangent Sn-Pg, S-line (Steiner), E-line (Riketts) and a facial angle according to Arnett. RESULTS The significant differences in profiles of persons with class II division 2 compared to class I were: position and prominence of the chin, the position of the lower and upper lip in relation to the S-line, and smaller value of a facial angle in relation to persons with class I. CONCLUSIONS The differences seen in skeletal profiles were not associated with significant differences in the profiled facial contours of the examined groups. The compensatory role of the fullness of soft tissues of the lips is probably the reason why there were not significant deviations in all the examined parameters.

  17. JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants

    DEFF Research Database (Denmark)

    Sundqvist, Emilie; Buck, Dorothea; Warnke, Clemens

    2014-01-01

    sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15)) and controls (OR = 0.53, p = 2×10(-5)). In contrast...

  18. The Duffy binding protein (PkDBPαII) of Plasmodium knowlesi from Peninsular Malaysia and Malaysian Borneo show different binding activity level to human erythrocytes.

    Science.gov (United States)

    Lim, Khai Lone; Amir, Amirah; Lau, Yee Ling; Fong, Mun Yik

    2017-08-11

    The zoonotic Plasmodium knowlesi is a major cause of human malaria in Malaysia. This parasite uses the Duffy binding protein (PkDBPαII) to interact with the Duffy antigen receptor for chemokines (DARC) receptor on human and macaque erythrocytes to initiate invasion. Previous studies on P. knowlesi have reported distinct Peninsular Malaysia and Malaysian Borneo PkDBPαII haplotypes. In the present study, the differential binding activity of these haplotypes with human and macaque (Macaca fascicularis) erythrocytes was investigated. The PkDBPαII of Peninsular Malaysia and Malaysian Borneo were expressed on the surface of COS-7 cells and tested with human and monkey erythrocytes, with and without anti-Fy6 (anti-Duffy) monoclonal antibody treatment. Binding activity level was determined by counting the number of rosettes formed between the transfected COS-7 cells and the erythrocytes. Anti-Fy6 treatment was shown to completely block the binding of human erythrocytes with the transfected COS-7 cells, thus verifying the specific binding of human DARC with PkDBPαII. Interestingly, the PkDBPαII of Peninsular Malaysia displayed a higher binding activity with human erythrocytes when compared with the Malaysian Borneo PkDBPαII haplotype (mean number of rosettes formed = 156.89 ± 6.62 and 46.00 ± 3.57, respectively; P < 0.0001). However, no difference in binding activity level was seen in the binding assay using M. fascicularis erythrocytes. This study is the first report of phenotypic difference between PkDBPαII haplotypes. The biological implication of this finding is yet to be determined. Therefore, further studies need to be carried out to determine whether this differential binding level can be associated with severity of knowlesi malaria in human.

  19. Human Reliability analysis for digitized nuclear power plants: Case study on the LingAo II nuclear power plant

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Yan Hua; Zhang, Li [Institute of Human Factors Engineering AND Safety Management, Hunan Institute of Technology, Hengyang (China); Dai, Cao; Li, Peng Cheng; Qing, Tao [Human Factors Institute, University of South China, Hengyang (China)

    2017-03-15

    The main control room (MCR) in advanced nuclear power plants (NPPs) has changed from analog to digital control system (DCS). Operation and control have become more automated, centralized, and accurate due to the digitalization of NPPs, which has improved the efficiency and security of the system. New issues associated with human reliability inevitably arise due to the adoption of new accident procedures and digitalization of main control rooms in NPPs. The LingAo II NPP is the first digital NPP in China to apply the state-oriented procedure. In order to address issues related to human reliability analysis for DCS and DCS + state-oriented procedure, the Hunan Institute of Technology conducted a research project based on a cooperative agreement with the LingDong Nuclear Power Co. Ltd. This paper is a brief introduction to the project.

  20. Human Reliability Analysis for Digitized Nuclear Power Plants: Case Study on the LingAo II Nuclear Power Plant

    Directory of Open Access Journals (Sweden)

    Yanhua Zou

    2017-03-01

    Full Text Available The main control room (MCR in advanced nuclear power plants (NPPs has changed from analog to digital control system (DCS. Operation and control have become more automated, centralized, and accurate due to the digitalization of NPPs, which has improved the efficiency and security of the system. New issues associated with human reliability inevitably arise due to the adoption of new accident procedures and digitalization of main control rooms in NPPs. The LingAo II NPP is the first digital NPP in China to apply the state-oriented procedure. In order to address issues related to human reliability analysis for DCS and DCS + state-oriented procedure, the Hunan Institute of Technology conducted a research project based on a cooperative agreement with the LingDong Nuclear Power Co. Ltd. This paper is a brief introduction to the project.

  1. Nephrin expression is reduced in human diabetic nephropathy: evidence for a distinct role for glycated albumin and angiotensin II.

    Science.gov (United States)

    Doublier, Sophie; Salvidio, Gennaro; Lupia, Enrico; Ruotsalainen, Vesa; Verzola, Daniela; Deferrari, Giacomo; Camussi, Giovanni

    2003-04-01

    We studied the distribution of nephrin in renal biopsies from 17 patients with diabetes and nephrotic syndrome (7 type 1 and 10 type 2 diabetes), 6 patients with diabetes and microalbuminuria (1 type 1 and 5 type 2 diabetes), and 10 normal subjects. Nephrin expression was semiquantitatively evaluated by measuring immunofluorescence intensity by digital image analysis. We found an extensive reduction of nephrin staining in both type 1 (67 +/- 9%; P < 0.001) and type 2 (65 +/- 10%; P < 0.001) diabetic patients with diabetes and nephrotic syndrome when compared with control subjects. The pattern of staining shifted from punctate/linear distribution to granular. In patients with microalbuminuria, the staining pattern of nephrin also showed granular distribution and reduction intensity of 69% in the patient with type 1 diabetes and of 62 +/- 4% (P < 0.001) in the patients with type 2 diabetes. In vitro studies on human cultured podocytes demonstrated that glycated albumin and angiotensin II reduced nephrin expression. Glycated albumin inhibited nephrin synthesis through the engagement of receptor for advanced glycation end products, whereas angiotensin II acted on cytoskeleton redistribution, inducing the shedding of nephrin. This study indicates that the alteration in nephrin expression is an early event in proteinuric patients with diabetes and suggests that glycated albumin and angiotensin II contribute to nephrin downregulation.

  2. Building human resources capability in health care: a global analysis of best practice--Part II.

    Science.gov (United States)

    Zairi, M

    1998-01-01

    This paper is the second from a series of three, addressing human resource practices using best practice examples. The analysis covered is based on the experiences of organisations that have won the Malcolm Baldrige National Quality Award (MBNQA) in the USA. The subcriteria covered in this benchmarking comparative analysis covers the following areas: human resource planning and management; employee involvement; employee education and training; employee performance and recognition; employee wellbeing and satisfaction. The paper concludes by reflecting on the likely implications for health-care professionals working in the human resource field.

  3. Histone acetyltransferase (HAT) activity of p300 modulates human T lymphotropic virus type 1 p30II-mediated repression of LTR transcriptional activity

    International Nuclear Information System (INIS)

    Michael, Bindhu; Nair, Amrithraj M.; Datta, Antara; Hiraragi, Hajime; Ratner, Lee; Lairmore, Michael D.

    2006-01-01

    Human T-lymphotropic virus type-1 (HTLV-1) is a deltaretrovirus that causes adult T cell leukemia/lymphoma, and is implicated in a variety of lymphocyte-mediated inflammatory disorders. HTLV-1 provirus has regulatory and accessory genes in four pX open reading frames. HTLV-1 pX ORF-II encodes two proteins, p13 II and p30 II , which are incompletely defined in virus replication or pathogenesis. We have demonstrated that pX ORF-II mutations block virus replication in vivo and that ORF-II encoded p30 II , a nuclear-localizing protein that binds with CREB-binding protein (CBP)/p300, represses CREB and Tax responsive element (TRE)-mediated transcription. Herein, we have identified p30 II motifs important for p300 binding and in regulating TRE-mediated transcription in the absence and presence of HTLV-1 provirus. Within amino acids 100-179 of p30 II , a region important for repression of LTR-mediated transcription, we identified a single lysine residue at amino acid 106 (K3) that significantly modulates the ability of p30 II to repress TRE-mediated transcription. Exogenous p300, in a dose-responsive manner, reverses p30 II -dependent repression of TRE-mediated transcription, in the absence or presence of the provirus, In contrast to wild type p300, p300 HAT mutants (defective in histone acetyltransferase activity) only partially rescued p30 II -mediated LTR repression. Deacetylation by histone deacetylase-1 (HDAC-1) enhanced p30 II -mediated LTR repression, while inhibition of deacetylation by trichostatin A decreases p30 II -mediated LTR repression. Collectively, our data indicate that HTLV-1 p30 II modulates viral gene expression in a cooperative manner with p300-mediated acetylation

  4. Política, marketing e neoliberalismo

    Directory of Open Access Journals (Sweden)

    Pedro Roberto Ferreira

    2004-07-01

    Full Text Available O texto contém uma análise da relação política e sua possível consciência no seu momento específico compreendido pelo processo eleitoral (Londrina - eleições 92. Como este processo eleitoral em nossos dias, nutre-se de algumas técnicas conhecidas como Marketing Político-Eleitoral, e de como estas, contribuem para uma dinâmica de esvaziamento da vida política propriamente dita. Procura ainda, conectar esse esvaziamento político e suas consequências, com o avanço da concepção neoliberal cujo ápice parece fazer coincidir a política como mais uma manifestação de Mercado.

  5. Human factors analysis and design methods for nuclear waste retrieval systems. Volume II. A compendium of human factors design data

    International Nuclear Information System (INIS)

    Casey, S.M.

    1980-04-01

    This document is a compilation of human factors engineering design recommendations and data, selected and organized to assist in the design of a nuclear waste retrieval system. Design guidelines from a variety of sources have been evaluated, edited, and expanded for inclusion in this document, and, where appropriate, portions of text from selected sources have been included in their entirety. A number of human factors engineering guidelines for equipment designers have been written over the past three decades, each tailored to the needs of the specific system being designed. In the case of this particular document, a review of the preliminary human operator functions involved in each phase of the retrieval process was performed, resulting in the identification of areas of design emphasis upon which this document should be based. Documents containing information and design data on each of these areas were acquired, and data and design guidelines related to the previously identified areas of emphasis were extracted and reorganized. For each system function, actions were first assigned to operator and/or machine, and the operator functions were then described. Separate lists of operator functions were developed for each of the areas of retrieval activities - survey and mapping, remining, floor flange emplacement, plug and canister overcoring, plug and canister removal and transport, and CWSRS activity. These functions and the associated man-machine interface were grouped into categories based on task similarity, and the principal topics of human factors design emphasis were extracted. These topic areas are reflected in the contents of the 12 sections of this document

  6. Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice

    Directory of Open Access Journals (Sweden)

    Mühlfeld Christian

    2007-10-01

    Full Text Available Abstract Background Surfactant protein D (SP-D deficient mice develop emphysema-like pathology associated with focal accumulations of foamy alveolar macrophages, an excess of surfactant phospholipids in the alveolar space and both hypertrophy and hyperplasia of alveolar type II cells. These findings are associated with a chronic inflammatory state. Treatment of SP-D deficient mice with a truncated recombinant fragment of human SP-D (rfhSP-D has been shown to decrease the lipidosis and alveolar macrophage accumulation as well as production of proinflammatory chemokines. The aim of this study was to investigate if rfhSP-D treatment reduces the structural abnormalities in parenchymal architecture and type II cells characteristic of SP-D deficiency. Methods SP-D knock-out mice, aged 3 weeks, 6 weeks and 9 weeks were treated with rfhSP-D for 9, 6 and 3 weeks, respectively. All mice were sacrificed at age 12 weeks and compared to both PBS treated SP-D deficient and wild-type groups. Lung structure was quantified by design-based stereology at the light and electron microscopic level. Emphasis was put on quantification of emphysema, type II cell changes and intracellular surfactant. Data were analysed with two sided non-parametric Mann-Whitney U-test. Main Results After 3 weeks of treatment, alveolar number was higher and mean alveolar size was smaller compared to saline-treated SP-D knock-out controls. There was no significant difference concerning these indices of pulmonary emphysema within rfhSP-D treated groups. Type II cell number and size were smaller as a consequence of treatment. The total volume of lamellar bodies per type II cell and per lung was smaller after 6 weeks of treatment. Conclusion Treatment of SP-D deficient mice with rfhSP-D leads to a reduction in the degree of emphysema and a correction of type II cell hyperplasia and hypertrophy. This supports the concept that rfhSP-D might become a therapeutic option in diseases that are

  7. Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

    Energy Technology Data Exchange (ETDEWEB)

    Ferramosca, Alessandra, E-mail: alessandra.ferramosca@unisalento.it [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Conte, Annalea; Guerra, Flora; Felline, Serena [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Rimoli, Maria Grazia [Dipartimento di Farmacia, Università di Napoli Federico II, Napoli (Italy); Mollo, Ernesto [Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli (Italy); Zara, Vincenzo [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Terlizzi, Antonio [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Stazione Zoologica Anton Dohrn, Napoli (Italy)

    2016-05-13

    The red pigment caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea can be accumulated and transferred along the trophic chain, with detrimental consequences on biodiversity and ecosystem functioning. Despite increasing research efforts to understand how caulerpin modifies fish physiology, little is known on the effects of algal metabolites on mammalian cells. Here we report for the first time the mitochondrial targeting activity of both caulerpin, and its closely related derivative caulerpinic acid, by using as experimental model rat liver mitochondria, a system in which bioenergetics mechanisms are not altered. Mitochondrial function was tested by polarographic and spectrophotometric methods. Both compounds were found to selectively inhibit respiratory complex II activity, while complexes I, III, and IV remained functional. These results led us to hypothesize that both algal metabolites could be used as antitumor agents in cell lines with defects in mitochondrial complex I. Ovarian cancer cisplatin-resistant cells are a good example of cell lines with a defective complex I function on which these molecules seem to have a toxic effect on proliferation. This provided novel insight toward the potential use of metabolites from invasive Caulerpa species for the treatment of human ovarian carcinoma cisplatin-resistant cells. -- Highlights: •Novel insight toward the potential use of the algal metabolites for the treatment of human diseases. •Caulerpin and caulerpinic acid inhibit respiratory complex II activity. •Both algal metabolites could be used as antitumor agents in ovarian cancer cisplatin-resistant cells.

  8. Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

    International Nuclear Information System (INIS)

    Ferramosca, Alessandra; Conte, Annalea; Guerra, Flora; Felline, Serena; Rimoli, Maria Grazia; Mollo, Ernesto; Zara, Vincenzo; Terlizzi, Antonio

    2016-01-01

    The red pigment caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea can be accumulated and transferred along the trophic chain, with detrimental consequences on biodiversity and ecosystem functioning. Despite increasing research efforts to understand how caulerpin modifies fish physiology, little is known on the effects of algal metabolites on mammalian cells. Here we report for the first time the mitochondrial targeting activity of both caulerpin, and its closely related derivative caulerpinic acid, by using as experimental model rat liver mitochondria, a system in which bioenergetics mechanisms are not altered. Mitochondrial function was tested by polarographic and spectrophotometric methods. Both compounds were found to selectively inhibit respiratory complex II activity, while complexes I, III, and IV remained functional. These results led us to hypothesize that both algal metabolites could be used as antitumor agents in cell lines with defects in mitochondrial complex I. Ovarian cancer cisplatin-resistant cells are a good example of cell lines with a defective complex I function on which these molecules seem to have a toxic effect on proliferation. This provided novel insight toward the potential use of metabolites from invasive Caulerpa species for the treatment of human ovarian carcinoma cisplatin-resistant cells. -- Highlights: •Novel insight toward the potential use of the algal metabolites for the treatment of human diseases. •Caulerpin and caulerpinic acid inhibit respiratory complex II activity. •Both algal metabolites could be used as antitumor agents in ovarian cancer cisplatin-resistant cells.

  9. Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines

    Science.gov (United States)

    Hernández, Wilfredo; Paz, Juan; Carrasco, Fernando; Spodine, Evgenia; Manzur, Jorge; Sieler, Joachim; Blaurock, Steffen; Beyer, Lothar

    2013-01-01

    The palladium(II) bis-chelate complexes of the type [Pd(TSC1-5)2] (6–10), with their corresponding ligands 4-phenyl-1-(acetone)-thiosemicarbazone, HTSC1 (1), 4-phenyl-1-(2′-chloro-benzaldehyde)-thiosemicarbazone, HTSC2 (2), 4-phenyl-1-(3′-hydroxy-benzaldehyde)-thiosemicarbazone, HTSC3 (3), 4-phenyl-1-(2′-naphthaldehyde)-thiosemicarbazone, HTSC4 (4), and 4-phenyl-1-(1′-nitro-2′-naphthaldehyde)-thiosemicarbazone, HTSC5 (5), were synthesized and characterized by elemental analysis and spectroscopic techniques (IR and 1H- and 13C-NMR). The molecular structure of HTSC3, HTSC4, and [Pd(TSC1)2] (6) have been determined by single crystal X-ray crystallography. Complex 6 shows a square planar geometry with two deprotonated ligands coordinated to PdII through the azomethine nitrogen and thione sulfur atoms in a cis arrangement. The in vitro cytotoxic activity measurements indicate that the palladium(II) complexes (IC50 = 0.01–9.87 μM) exhibited higher antiproliferative activity than their free ligands (IC50 = 23.48–70.86 and >250 μM) against different types of human tumor cell lines. Among all the studied palladium(II) complexes, the [Pd(TSC3)2] (8) complex exhibited high antitumor activity on the DU145 prostate carcinoma and K562 chronic myelogenous leukemia cells, with low values of the inhibitory concentration (0.01 and 0.02 μM, resp.). PMID:24391528

  10. Gene expression dose-response changes in microarrays after exposure of human peripheral lung epithelial cells to nickel(II).

    Science.gov (United States)

    Cheng, Robert Y S; Zhao, Ailian; Alvord, W Gregory; Powell, Douglas A; Bare, Robert M; Masuda, Akira; Takahashi, Takashi; Anderson, Lucy M; Kasprzak, Kazimierz S

    2003-08-15

    Occupational exposure to nickel compounds is associated with lung cancer risk; both genotoxic and epigenetic mechanisms have been proposed. For comprehensive examination of the acute effects of nickel(II) acetate on gene expression in cultured human peripheral lung epithelial HPL1D cells, microarray analyses were carried out with cDNA chips (approximately 8000 cDNAs). Cells were exposed for 24 h to nontoxic (50, 100, and 200 microM) or toxic (400, 800, and 1600 microM) nickel(II) concentrations. Cluster analysis was applied to the 868 genes with > or = 2-fold change at any concentration. Two main clusters showed marked up- or down-regulation at the highest, toxic concentrations. The data further subdivided into 10 highly cohesive clusters with high probability, and of these only 2 had the same response trend at low nontoxic as at high concentrations, an observation of clear relevance to the process of high- to low-dose extrapolation in risk assessment. There were 113 genes showing > or = 2-fold change at the three lower nontoxic concentrations, those most relevant to in vivo carcinogenesis. In addition to expected responses of metallothionein, ferritin, and heat-shock proteins, the results revealed for the first time changed expression of some potential cancer-related genes in response to low-dose Ni(II): RhoA, dyskerin, interferon regulatory factor 1, RAD21 homologue, and tumor protein, translationally controlled. Overall, most of the genes impacted by nontoxic concentrations of nickel(II) acetate related to gene transcription, protein synthesis and stability, cytoskeleton, signaling, metabolism, cell membrane, and extracellular matrix.

  11. Biosynthesis of 10 kDa and 7.5 kDa insulin-like growth factor II in a human rhabdomyosarcoma cell line

    DEFF Research Database (Denmark)

    Nielsen, F C; Haselbacher, G; Christiansen, Jan

    1993-01-01

    In the present study we have analysed the expression of insulin-like growth factor II (IGF-II) in the human rhabdomyosarcoma cell line IN157.IN157 cells express high levels of three IGF-II mRNAs of 6.0 kb, 4.8 kb and 4.2 kb. In contrast, normal skeletal muscle expresses a negligible amount of IGF......-II mRNA. Two forms of IGF-II with molecular masses of 7.5 kDa and 10 kDa, corresponding to the mature IGF-II and IGF-II with a C-terminal extension of 21 amino acids (IGF-IIE21), were secreted into the culture medium at amounts of 17 ng/ml (2.3 nM) and 15 ng/ml (1.5 nM), respectively. IN157 cells also......-II and IGF-IIE21 with Kd values of 0.5 nM and 2 nM, respectively, and IGF-I with about 500 times lower affinity. IGF-II and IGF-IIE21 stimulated DNA synthesis via the IGF-I receptor, whereas the IGF-II/Man 6-P receptor mediated their rapid internalization and inactivation. During culture of IN157 cells about...

  12. Relationship between RNA polymerase II and efficiency of vaccinia virus replication

    International Nuclear Information System (INIS)

    Wilton, S.; Dales, S.

    1989-01-01

    It is clear from previous studies that host transcriptase or RNA polymerase II (pol II) has a role in poxvirus replication. To elucidate the participation of this enzyme further, in this study the authors examined several parameters related to pol II during the cycle of vaccinia virus infection in L-strain fibroblasts, HeLa cells, and L 6 H 9 rat myoblasts. Nucleocytoplasmic transposition of pol II into virus factories and virions was assessed by immunofluorescence and immunoblotting by using anti-pol II immunoglobulin G. RNA polymerase activities were compared in nuclear extracts containing cured enzyme preparations. Rates of translation into cellular or viral polypeptides were ascertained by labeling with [ 35 S]methionine. In L and HeLa cells, which produced vaccinia virus more abundantly, the rate of RNA polymerase and translation in controls and following infection were higher than in myoblasts. The data on synthesis and virus formation could be correlated with observations on transmigration of pol II, which was more efficient and complete in L and HeLa cells. The stimulus for pol II to leave the nucleus required the expression of both early and late viral functions. On the basis of current and past information, the authors suggest that mobilization of pol II depends on the efficiency of vaccinia virus replication and furthermore that control over vaccinia virus production by the host is related to the content or availability (or both) of pol II in different cell types

  13. Angiotensin II Regulates microRNA-132/-212 in Hypertensive Rats and Humans

    DEFF Research Database (Denmark)

    Eskildsen, Tilde V; Jeppesen, Pia L; Schneider, Mikael

    2013-01-01

    MicroRNAs (miRNAs), a group of small non-coding RNAs that fine tune translation of multiple target mRNAs, are emerging as key regulators in cardiovascular development and disease. MiRNAs are involved in cardiac hypertrophy, heart failure and remodeling following cardiac infarction; however, mi...... no effect. Taken together, these data suggest that miR-132 and miR-212 are involved in AngII induced hypertension, providing a new perspective in hypertensive disease mechanisms....

  14. Regulatory T cells in human and angiotensin II-induced mouse abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Zhou, Yi; Wu, Wenxue; Lindholt, Jes S

    2015-01-01

    concentration in blood cell lysates from 485 AAA patients and 204 age- and sex-matched controls. AAA patients exhibited lower blood cell Foxp3 expression than controls (P Pearson's correlation test demonstrated a significant but negative correlation between Foxp3 and AAA annual expansion rate before...... (r = -0.147, P = 0.007) and after (r = -0.153, P = 0.006) adjustment for AAA risk factors. AAA in apolipoprotein E-deficient (Apoe(-/-)) mice that received different doses of Ang-II exhibited a negative correlation of lesion Foxp3(+) Treg numbers with AAA size (r = -0.883, P

  15. Recombinant pollen allergens from Dactylis glomerata: preliminary evidence that human IgE cross-reactivity between Dac g II and Lol p I/II is increased following grass pollen immunotherapy.

    Science.gov (United States)

    Roberts, A M; Van Ree, R; Cardy, S M; Bevan, L J; Walker, M R

    1992-07-01

    We previously described the isolation of three identical complementary DNA (cDNA) clones, constructed from Orchard/Cocksfoot grass (Dactylis glomerata) anther messenger RNA (mRNA), expressing a 140,000 MW beta-galactosidase fusion protein recognized by IgE antibodies in atopic sera. Partial nucleotide sequencing and inferred amino acid sequence showed greater than 90% homology with the group II allergen from Lolium perenne (Lol II) indicating they encode the group II equivalent, Dac g II. Western blot immunoprobing of recombinant lysates with rabbit polyclonal, mouse monoclonal and human polyclonal antisera demonstrates immunological identity between recombinant Dac g II, Lol p I and Lol p II. Similar cross-identity is observed with pollen extracts from three other grass species: Festuca rubra, Phleum pratense and Anthoxanthum odoratum. Recombinant Dac g II was recognized by species- and group-cross-reactive human IgE antibodies in 33% (4/12) of sera randomly selected from grass-sensitive individuals and in 67% (14/21) of sera from patients receiving grass pollen immunotherapy, whilst 0/4 sera from patients receiving venom immunotherapy alone contained Dac g II cross-reactive IgE. Cross-reactive IgG4 antibodies were detectable in 95% of sera from grass pollen immunotherapy patients. These preliminary data suggest that conventional grass pollen allergoid desensitization immunotherapy may induce IgE responses to a cross-reactive epitope(s) co-expressed by grass pollen groups I and II (and possibly group III) allergens.

  16. Reconstitution of active human core Mediator complex reveals a pivotal role of the MED14 subunit

    Science.gov (United States)

    Cevher, Murat A.; Shi, Yi; Li, Dan; Chait, Brian T.; Malik, Sohail; Roeder, Robert G.

    2014-01-01

    The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here, we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to mass spectrometry (CX-MS). Whereas the reconstituted head and middle modules can stably associate, only with incorporation of MED14 into the bi-modular complex does it acquire basal and coactivator functions. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematically dissecting the multiple layers of functionalities associated with the Mediator complex. PMID:25383669

  17. Reconstitution of active human core Mediator complex reveals a critical role of the MED14 subunit.

    Science.gov (United States)

    Cevher, Murat A; Shi, Yi; Li, Dan; Chait, Brian T; Malik, Sohail; Roeder, Robert G

    2014-12-01

    The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to MS (CX-MS). Whereas the reconstituted head and middle modules can stably associate, basal and coactivator functions are acquired only after incorporation of MED14 into the bimodular complex. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematic dissection of the multiple layers of functionality associated with the Mediator complex.

  18. Edad y cultura política

    Directory of Open Access Journals (Sweden)

    MANUEL JUSTEL

    1992-01-01

    Full Text Available En este artículo se analiza la evolución de algunos aspectos de la cultura política y democrática durante los años ochenta: información y competencia política, participación política, actitudes hacia los partidos y orientaciones políticas. Los datos proceden de sendas encuestas realizadas en 1980 y 1989. Mediante análisis de cohortes de edad, controlando sexo y nivel de estudios, se comprueba el grado diferencial de expansión de actitudes democráticas en los grupos de edad, controlando sexo y nivel de estudios, se comprueba el grado diferencial de expansión de actitudes democráticas en los grupos de edad, el efecto homogeneizador que conlleva y el influjo estratégico de la educación. En el marco teórico de la socialización política en edad adulta y de las relaciones entre sistema social y sistema político, se interpretan los cambios de actitudes distinguiendo efectos de ciclo vital, de cohorte y de periodo. Al mismo tiempo, se discuten algunas consecuencias políticas del envejecimiento poblacional y se constata de un grado notable de plasticidad actitudinal y de adhesión creciente a la democracia de las cohortes de edad avanzada.

  19. Observatorio de Política Internacional I. COLOMBIA - Una paz esquiva

    OpenAIRE

    Neira Fernández, Enrique

    2007-01-01

    Observatorio de Política Internacional I. COLOMBIA (Neira Fernández, Enrique) RECIENTES Año 2008 Colombia. Cerca el fin del paramilitarismo Colombia. Cerca el fin de las Farc Colombia. Conflicto armado y desarrollo humano Colombia. Política exterior Colombia. Inicia el 2008 con buen pie Año 2007 Colombia. Tras las pasadas elecciones Colombia. El espectro de las próximas elecciones Colombia. La garrocha de Uribe Colombia. III Parapolíticos Colombia. II...

  20. Observatorio de Política Internacional I. COLOMBIA - Una nueva estrategia de paz

    OpenAIRE

    Neira Fernández, Enrique

    2007-01-01

    Observatorio de Política Internacional I. COLOMBIA (Neira Fernández, Enrique) RECIENTES Año 2008 Colombia. Cerca el fin del paramilitarismo Colombia. Cerca el fin de las Farc Colombia. Conflicto armado y desarrollo humano Colombia. Política exterior Colombia. Inicia el 2008 con buen pie Año 2007 Colombia. Tras las pasadas elecciones Colombia. El espectro de las próximas elecciones Colombia. La garrocha de Uribe Colombia. III Parapolíticos Colombia. II...

  1. Observatorio de Política Internacional I. COLOMBIA - Una paz secuestrada

    OpenAIRE

    Neira Fernández, Enrique

    2007-01-01

    Observatorio de Política Internacional I. COLOMBIA (Neira Fernández, Enrique) RECIENTES Año 2008 Colombia. Cerca el fin del paramilitarismo Colombia. Cerca el fin de las Farc Colombia. Conflicto armado y desarrollo humano Colombia. Política exterior Colombia. Inicia el 2008 con buen pie Año 2007 Colombia. Tras las pasadas elecciones Colombia. El espectro de las próximas elecciones Colombia. La garrocha de Uribe Colombia. III Parapolíticos Colombia. II...

  2. Observatorio de Política Internacional I. COLOMBIA - Los momentos de la paz

    OpenAIRE

    Neira Fernández, Enrique

    2012-01-01

    Observatorio de Política Internacional I. COLOMBIA (Neira Fernández, Enrique) RECIENTES Año 2008 Colombia. Cerca el fin del paramilitarismo Colombia. Cerca el fin de las Farc Colombia. Conflicto armado y desarrollo humano Colombia. Política exterior Colombia. Inicia el 2008 con buen pie Año 2007 Colombia. Tras las pasadas elecciones Colombia. El espectro de las próximas elecciones Colombia. La garrocha de Uribe Colombia. III Parapolíticos Colombia. II...

  3. Observatorio de Política Internacional I. COLOMBIA - Siempre es tarde para la paz

    OpenAIRE

    Neira Fernández, Enrique

    2007-01-01

    Observatorio de Política Internacional I. COLOMBIA (Neira Fernández, Enrique) RECIENTES Año 2008 Colombia. Cerca el fin del paramilitarismo Colombia. Cerca el fin de las Farc Colombia. Conflicto armado y desarrollo humano Colombia. Política exterior Colombia. Inicia el 2008 con buen pie Año 2007 Colombia. Tras las pasadas elecciones Colombia. El espectro de las próximas elecciones Colombia. La garrocha de Uribe Colombia. III Parapolíticos Colombia. II...

  4. Observatorio de Política Internacional I. COLOMBIA - Viraje en el proceso de paz

    OpenAIRE

    Neira Fernández, Enrique

    2007-01-01

    Observatorio de Política Internacional I. COLOMBIA (Neira Fernández, Enrique) RECIENTES Año 2008 Colombia. Cerca el fin del paramilitarismo Colombia. Cerca el fin de las Farc Colombia. Conflicto armado y desarrollo humano Colombia. Política exterior Colombia. Inicia el 2008 con buen pie Año 2007 Colombia. Tras las pasadas elecciones Colombia. El espectro de las próximas elecciones Colombia. La garrocha de Uribe Colombia. III Parapolíticos Colombia. II...

  5. Human brain as the model of a new computer system. II

    Energy Technology Data Exchange (ETDEWEB)

    Holtz, K; Langheld, E

    1981-12-09

    For Pt. I see IBID., Vol. 29, No. 22, P. 13 (1981). The authors describe the self-generating system of connections of a self-teaching no-program associative computer. The self-generating systems of connections are regarded as simulation models of the human brain and compared with the brain structure. The system hardware comprises microprocessor, PROM, memory, VDU, keyboard unit.

  6. Proteomic analysis of human metaphase chromosomes reveals Topoisomerase II alpha as an Aurora B substrate

    DEFF Research Database (Denmark)

    Morrison, Ciaran; Henzing, Alexander J; Jensen, Ole Nørregaard

    2002-01-01

    B in the presence of radioactive ATP. Immunoblot analysis confirmed the HeLa scaffold fraction to be enriched for known chromosomal proteins including CENP-A, CENP-B, CENP-C, ScII and INCENP. Mass spectrometry of bands excised from one-dimensional polyacrylamide gels further defined the protein......The essential Aurora B kinase is a chromosomal passenger protein that is required for mitotic chromosome alignment and segregation. Aurora B function is dependent on the chromosome passenger, INCENP. INCENP, in turn, requires sister chromatid cohesion for its appropriate behaviour. Relatively few...... composition of the extracted chromosome fraction. Cloning, fluorescent tagging and expression in HeLa cells of the putative GTP-binding protein NGB/CRFG demonstrated it to be a novel mitotic chromosome protein, with a perichromosomal localisation. Identi fication of the protein bands corresponding to those...

  7. The politics of protection: aid, human rights discourse, and power relations in Kyaka II settlement, Uganda.

    Science.gov (United States)

    Clark-Kazak, Christina R

    2010-01-01

    This paper explores the conceptualisation and application of 'protection' by the United Nations High Commissioner (UNHCR), Ugandan government, and Congolese refugees in Kyaka II refugee settlement, Uganda. Analysing the origins and consequences of a demonstration against school fees, and drawing on other ethnographic data, it explores how different interpretations of this incident reflect different conceptions of, and approaches to, protection. Ugandan government officials viewed the demonstration as a security incident; Congolese and Ugandan adults responded with increased monitoring and 'sheltering' of children and young people; students justified the demonstration as a legitimate manifestation of their rights; while UNHCR promoted assistance and resettlement. The paper argues that prevailing protection responses, including 'sensitisation', sheltering, and resettlement, are de-contextualised from daily realities and fail to address the underlying power relations that undermine protection. It concludes with recommendations on how international refugee agencies can reorient assistance to address protection concerns in refugee contexts.

  8. The effect of 3'- methyl-N,N-dimethylaminoasobenzene and gamma rays on the serum level of deoxyribonuclease II of the rat and the isolation of deoxyribonuclease II from the human spleen

    International Nuclear Information System (INIS)

    Jansen van Rensburg, E.

    1979-01-01

    The purpose of this investigation was twofold, viz.: 1. To determine the influence of ionising radiation (physical carcinogen) on deoxyribonuclease II in serum. 2. To develop a sensitive method for determining deoxyribonuclease II, viz. a radioimmunoassay (RlA). With this object in view, the influence of a strong physical carcinogen, viz. 60 Co gamma rays, on the activity of DNase II in rat serum was studied. For comparative studies, the influence of a strong chemical carcinogen (3'-methyl-N,N-dimethylaminoasobenzene) on rat serum DNase II was determined. In addition, attempts were made to isolate, purify and characterise DNase II from human spleen. These attempts were made as the first step in the development of a RlA. The in vivo studies of the influence of 3'MeDAB over a long period (40 weeks) showed that the DNase II activity increased in the serum and liver nuclei of rats during the pre-cancer phase. This increase may, together with other parameters, be useful in the early diagnosis of liver cancer. The most important contribution of this investigation is the possible use of a serum DNase II RlA together with a battery RlAs for other indicators (biochemical) for the determination of radiation exposure in man [af

  9. Bioinformatic Analysis of Plasma Apolipoproteins A-I and A-II Revealed Unique Features of A-I/A-II HDL Particles in Human Plasma

    Science.gov (United States)

    Kido, Toshimi; Kurata, Hideaki; Kondo, Kazuo; Itakura, Hiroshige; Okazaki, Mitsuyo; Urata, Takeyoshi; Yokoyama, Shinji

    2016-01-01

    Plasma concentration of apoA-I, apoA-II and apoA-II-unassociated apoA-I was analyzed in 314 Japanese subjects (177 males and 137 females), including one (male) homozygote and 37 (20 males and 17 females) heterozygotes of genetic CETP deficiency. ApoA-I unassociated with apoA-II markedly and linearly increased with HDL-cholesterol, while apoA-II increased only very slightly and the ratio of apoA-II-associated apoA-I to apoA-II stayed constant at 2 in molar ratio throughout the increase of HDL-cholesterol, among the wild type and heterozygous CETP deficiency. Thus, overall HDL concentration almost exclusively depends on HDL with apoA-I without apoA-II (LpAI) while concentration of HDL containing apoA-I and apoA-II (LpAI:AII) is constant having a fixed molar ratio of 2 : 1 regardless of total HDL and apoA-I concentration. Distribution of apoA-I between LpAI and LpAI:AII is consistent with a model of statistical partitioning regardless of sex and CETP genotype. The analysis also indicated that LpA-I accommodates on average 4 apoA-I molecules and has a clearance rate indistinguishable from LpAI:AII. Independent evidence indicated LpAI:A-II has a diameter 20% smaller than LpAI, consistent with a model having two apoA-I and one apoA-II. The functional contribution of these particles is to be investigated. PMID:27526664

  10. Gene expression profiling associated with angiotensin II type 2 receptor-induced apoptosis in human prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Nana Pei

    Full Text Available Increased expression of angiotensin II type 2 receptor (AT2R induces apoptosis in numerous tumor cell lines, with either Angiotensin II-dependent or Angiotensin II-independent regulation, but its molecular mechanism remains poorly understood. Here, we used PCR Array analysis to determine the gene and microRNA expression profiles in human prostate cancer cell lines transduced with AT2R recombinant adenovirus. Our results demonstrated that AT2R over expression leads to up-regulation of 6 apoptosis-related genes (TRAIL-R2, BAG3, BNIPI, HRK, Gadd45a, TP53BP2, 2 cytokine genes (IL6 and IL8 and 1 microRNA, and down-regulation of 1 apoptosis-related gene TNFSF10 and 2 cytokine genes (BMP6, BMP7 in transduced DU145 cells. HRK was identified as an up-regulated gene in AT2R-transduced PC-3 cells by real-time RT-PCR. Next, we utilized siRNAs to silence the up-regulated genes to further determine their roles on AT2R overexpression mediated apoptosis. The results showed downregulation of Gadd45a reduced the apoptotic effect by ∼30% in DU145 cells, downregulation of HRK reduced AT2R-mediated apoptosis by more than 50% in PC-3 cells, while downregulation of TRAIL-R2 enhanced AT2R-mediated apoptosis more than 4 times in DU145 cells. We also found that the effects on AT2R-mediated apoptosis caused by downregulation of Gadd45a, TRAIL-R2 and HRK were independent in activation of p38 MAPK, p44/42 MAPK and p53. Taken together, our results demonstrated that TRAIL-R2, Gadd45a and HRK may be novel target genes for further study of the mechanism of AT2R-mediated apoptosis in prostate cancer cells.

  11. Muscle protein analysis. II. Two-dimensional electrophoresis of normal and diseased human skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Giometti, C.S. (Argonne National Lab., IL); Barany, M.; Danon, M.J.; Anderson, N.G.

    1980-07-01

    High-resolution two-dimensional electrophoresis was used to analyze the major proteins of normal and pathological human-muscle samples. The normal human-muscle pattern contains four myosin light chains: three that co-migrate with the myosin light chains from rabbit fast muscle (extensor digitorum longus), and one that co-migrates with the light chain 2 from rabbit slow muscle (soleus). Of seven Duchenne muscular dystrophy samples, four yielded patterns with decreased amounts of actin and myosin relative to normal muscle, while three samples gave patterns comparable to that for normal muscle. Six samples from patients with myotonic dystrophy also gave normal patterns. In nemaline rod myopathy, in contrast, the pattern was deficient in two of the fast-type myosin light chains.

  12. Morphological analysis of the hindlimb in apes and humans. II. Moment arms

    Science.gov (United States)

    Payne, R C; Crompton, R H; Isler, K; Savage, R; Vereecke, E E; Günther, M M; Thorpe, S K S; D'Août, K

    2006-01-01

    Flexion/extension moment arms were obtained for the major muscles crossing the hip, knee and ankle joints in the orang-utan, gibbon, gorilla (Eastern and Western lowland) and bonobo. Moment arms varied with joint motion and were generally longer in proximal limb muscles than distal limb muscles. The shape of the moment arm curves (i.e. the plots of moment arm against joint angle) differed in different hindlimb muscles and in the same muscle in different subjects (both in the same and in different ape species). Most moment arms increased with increasing joint flexion, a finding which may be understood in the context of the employment of flexed postures by most non-human apes (except orang-utans) during both terrestrial and arboreal locomotion. When compared with humans, non-human great apes tended to have muscles better designed for moving the joints through large ranges. This was particularly true of the pedal digital flexors in orang-utans. In gibbons, the only lesser ape studied here, many of the moment arms measured were relatively short compared with those of great apes. This study was performed on a small sample of apes and thus differences noted here warrant further investigation in larger populations. PMID:16761974

  13. Study on the interaction of a copper(II) complex containing the artificial sweetener aspartame with human serum albumin.

    Science.gov (United States)

    Shahabadi, Nahid; Khodaei, Mohammad Mehdi; Kashanian, Soheila; Kheirdoosh, Fahimeh; Filli, Soraya Moradi

    2014-05-01

    A copper(II) complex containing aspartame (APM) as ligand, Cu(APM)2Cl2·2H2O, was synthesized and characterized. In vitro binding interaction of this complex with human serum albumin (HSA) was studied at physiological pH. Binding studies of this complex with HSA are useful for understanding the Cu(APM)2Cl2·2H2O-HSA interaction mechanism and providing guidance for the application and design of new and more efficient artificial sweeteners drive. The interaction was investigated by spectrophotometric, spectrofluorometric, competition experiment and circular dichroism. Hyperchromicity observed in UV absorption band of Cu(APM)2Cl2·2H2O. A strong fluorescence quenching reaction of HSA to Cu(APM)2Cl2·2H2O was observed and the binding constant (Kf) and corresponding numbers of binding sites (n) were calculated at different temperatures. Thermodynamic parameters, enthalpy change (∆H) and entropy change (∆S) were calculated to be -458.67 kJ mol(-1) and -1,339 J mol(-1 )K(-1) respectively. According to the van't Hoff equation, the reaction is predominantly enthalpically driven. In conformity with experimental results, we suggest that Cu(APM)2Cl2·2H2O interacts with HSA. In comparison with previous study, it is found that the Cu(II) complex binds stronger than aspartame.

  14. Human T lymphotropic virus type-1 p30II alters cellular gene expression to selectively enhance signaling pathways that activate T lymphocytes

    Directory of Open Access Journals (Sweden)

    Feuer Gerold

    2004-11-01

    Full Text Available Abstract Background Human T-lymphotropic virus type-1 (HTLV-1 is a deltaretrovirus that causes adult T-cell leukemia/lymphoma and is implicated in a variety of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13II and p30II, which are incompletely defined in the virus life cycle or HTLV-1 pathogenesis. Proviral clones of the virus with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. Exogenous expression of p30II differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and represses tax/rex RNA nuclear export. Results Herein, we further characterized the role of p30II in regulation of cellular gene expression, using stable p30II expression system employing lentiviral vectors to test cellular gene expression with Affymetrix U133A arrays, representing ~33,000 human genes. Reporter assays in Jurkat T cells and RT-PCR in Jurkat and primary CD4+ T-lymphocytes were used to confirm selected gene expression patterns. Our data reveals alterations of interrelated pathways of cell proliferation, T-cell signaling, apoptosis and cell cycle in p30II expressing Jurkat T cells. In all categories, p30II appeared to be an overall repressor of cellular gene expression, while selectively increasing the expression of certain key regulatory genes. Conclusions We are the first to demonstrate that p30II, while repressing the expression of many genes, selectively activates key gene pathways involved in T-cell signaling/activation. Collectively, our data suggests that this complex retrovirus, associated with lymphoproliferative diseases, relies upon accessory gene products to modify cellular environment to promote clonal expansion of the virus genome and thus maintain proviral loads in vivo.

  15. A plasmid containing the human metallothionein II gene can function as an antibody-assisted electrophoretic biosensor for heavy metals.

    Science.gov (United States)

    Wooten, Dennis C; Starr, Clarise R; Lyon, Wanda J

    2016-01-01

    Different forms of heavy metals affect biochemical systems in characteristic ways that cannot be detected with typical metal analysis methods like atomic absorption spectrometry. Further, using living systems to analyze interaction of heavy metals with biochemical systems can be laborious and unreliable. To generate a reliable easy-to-use biologically-based biosensor system, the entire human metallothionein-II (MT-II) gene was incorporated into a plasmid (pUC57-MT) easily replicated in Escherichia coli. In this system, a commercial polyclonal antibody raised against human metal-responsive transcription factor-1 protein (MTF-1 protein) could modify the electrophoretic migration patterns (i.e. cause specific decreases in agarose gel electrophoretic mobility) of the plasmid in the presence or absence of heavy metals other than zinc (Zn). In the study here, heavy metals, MTF-1 protein, and polyclonal anti-MTF-1 antibody were used to assess pUC57-MT plasmid antibody-assisted electrophoretic mobility. Anti-MTF-1 antibody bound both MTF-1 protein and pUC57-MT plasmid in a non-competitive fashion such that it could be used to differentiate specific heavy metal binding. The results showed that antibody-inhibited plasmid migration was heavy metal level-dependent. Zinc caused a unique mobility shift pattern opposite to that of other metals tested, i.e. Zn blocked the antibody ability to inhibit plasmid migration, despite a greatly increased affinity for DNA by the antibody when Zn was present. The Zn effect was reversed/modified by adding MTF-1 protein. Additionally, antibody inhibition of plasmid mobility was resistant to heat pre-treatment and trypsinization, indicating absence of residual DNA extraction-resistant bacterial DNA binding proteins. DNA binding by anti-DNA antibodies may be commonly enhanced by xenobiotic heavy metals and elevated levels of Zn, thus making them potentially effective tools for assessment of heavy metal bioavailability in aqueous solutions and

  16. Identifying Effective Enzyme Activity Targets for Recombinant Class I and Class II Collagenase for Successful Human Islet Isolation.

    Science.gov (United States)

    Balamurugan, Appakalai N; Green, Michael L; Breite, Andrew G; Loganathan, Gopalakrishnan; Wilhelm, Joshua J; Tweed, Benjamin; Vargova, Lenka; Lockridge, Amber; Kuriti, Manikya; Hughes, Michael G; Williams, Stuart K; Hering, Bernhard J; Dwulet, Francis E; McCarthy, Robert C

    2016-01-01

    Isolation following a good manufacturing practice-compliant, human islet product requires development of a robust islet isolation procedure where effective limits of key reagents are known. The enzymes used for islet isolation are critical but little is known about the doses of class I and class II collagenase required for successful islet isolation. We used a factorial approach to evaluate the effect of high and low target activities of recombinant class I (rC1) and class II (rC2) collagenase on human islet yield. Consequently, 4 different enzyme formulations with divergent C1:C2 collagenase mass ratios were assessed, each supplemented with the same dose of neutral protease. Both split pancreas and whole pancreas models were used to test enzyme targets (n = 20). Islet yield/g pancreas was compared with historical enzymes (n = 42). Varying the Wunsch (rC2) and collagen degradation activity (CDA, rC1) target dose, and consequently the C1:C2 mass ratio, had no significant effect on tissue digestion. Digestions using higher doses of Wunsch and CDA resulted in comparable islet yields to those obtained with 60% and 50% of those activities, respectively. Factorial analysis revealed no significant main effect of Wunsch activity or CDA for any parameter measured. Aggregate results from 4 different collagenase formulations gave 44% higher islet yield (>5000 islet equivalents/g) in the body/tail of the pancreas (n = 12) when compared with those from the same segment using a standard natural collagenase/protease mixture (n = 6). Additionally, islet yields greater than 5000 islet equivalents/g pancreas were also obtained in whole human pancreas. A broader C1:C2 ratio can be used for human islet isolation than has been used in the past. Recombinant collagenase is an effective replacement for the natural enzyme and we have determined that high islet yield can be obtained even with low doses of rC1:rC2, which is beneficial for the survival of islets.

  17. Non-thermal Plasma Activates Human Keratinocytes by Stimulation of Antioxidant and Phase II Pathways

    Science.gov (United States)

    Schmidt, Anke; Dietrich, Stephan; Steuer, Anna; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Masur, Kai; Wende, Kristian

    2015-01-01

    Non-thermal atmospheric pressure plasma provides a novel therapeutic opportunity to control redox-based processes, e.g. wound healing, cancer, and inflammatory diseases. By spatial and time-resolved delivery of reactive oxygen and nitrogen species, it allows stimulation or inhibition of cellular processes in biological systems. Our data show that both gene and protein expression is highly affected by non-thermal plasma. Nuclear factor erythroid-related factor 2 (NRF2) and phase II enzyme pathway components were found to act as key controllers orchestrating the cellular response in keratinocytes. Additionally, glutathione metabolism, which is a marker for NRF2-related signaling events, was affected. Among the most robustly increased genes and proteins, heme oxygenase 1, NADPH-quinone oxidoreductase 1, and growth factors were found. The roles of NRF2 targets, investigated by siRNA silencing, revealed that NRF2 acts as an important switch for sensing oxidative stress events. Moreover, the influence of non-thermal plasma on the NRF2 pathway prepares cells against exogenic noxae and increases their resilience against oxidative species. Via paracrine mechanisms, distant cells benefit from cell-cell communication. The finding that non-thermal plasma triggers hormesis-like processes in keratinocytes facilitates the understanding of plasma-tissue interaction and its clinical application. PMID:25589789

  18. Cross-reactivity profiles of hybrid capture II, cobas, and APTIMA human papillomavirus assays

    DEFF Research Database (Denmark)

    Preisler, Sarah Nørgaard; Rebolj, Matejka; Ejegod, Ditte Møller

    2016-01-01

    evaluated to what extent these can be explained by cross-reactivity, i.e. positive test results without evidence of high-risk HPV genotypes. The patterns of cross-reactivity have been thoroughly studied for hybrid capture II (HC2) but not yet for newer HPV assays although the manufacturers claimed...... no or limited frequency of cross-reactivity. In this independent study we evaluated the frequency of cross-reactivity for HC2, cobas, and APTIMA assays. Methods Consecutive routine cervical screening samples from 5022 Danish women, including 2859 from women attending primary screening, were tested...... with normal cytology and positive high-risk HPV test results were invited for repeated testing in 18 months. Results Cross-reactivity to low-risk genotypes was detected in 109 (2.2 %) out of 5022 samples on HC2, 62 (1.2 %) on cobas, and 35 (0.7 %) on APTIMA with only 10 of the samples cross-reacting on all 3...

  19. Fuels and Petroleum, Oil & Lubricants (POL) Laboratories

    Data.gov (United States)

    Federal Laboratory Consortium — The Fuels and Lubricants Technology Team operates and maintains the Fuels and POL Labs at TARDEC. Lab experts adhere to standardized American Society for Testing and...

  20. Application of a new ultra-microculture system. II. Stimulation of human B lymphocytes.

    Science.gov (United States)

    Ulmer, A J; Gruber, M; Flad, H D

    1988-07-22

    An ultra-microtechnique for culturing human B-lymphocytes in glass capillary tubes using a volume of 2 microliter is described. The advantage of this ultra-microculture system is that only a small number of lymphocytes and minute amounts of culture medium (or test factors) are required. Optimal culture conditions for the formation of Ig-secreting plaque-forming cells (PFC) after stimulation of mononuclear cells with pokeweed mitogen are given. Furthermore it is shown that immunoglobulin secreted into culture supernatants by purified B cells in the presence of T cell subsets can be measured in a microELISA.

  1. Fingerprinting of near-homogeneous DNA ligase I and II from human cells. Similarity of their AMP-binding domains.

    Science.gov (United States)

    Yang, S W; Becker, F F; Chan, J Y

    1990-10-25

    DNA ligases play obligatory roles during replication, repair, and recombination. Multiple forms of DNA ligase have been reported in mammalian cells including DNA ligase I, the high molecular mass species which functions during replication, and DNA ligase II, the low molecular mass species which is associated with repair. In addition, alterations in DNA ligase activities have been reported in acute lymphocytic leukemia cells, Bloom's syndrome cells, and cells undergoing differentiation and development. To better distinguish the biochemical and molecular properties of the various DNA ligases from human cells, we have developed a method of purifying multiple species of DNA ligase from HeLa cells by chromatography through DEAE-Bio-Gel, CM-Bio-Gel, hydroxylapatite, Sephacryl S-300, Mono P, and DNA-cellulose. DNA-cellulose chromatography of the partially purified enzymes resolved multiple species of DNA ligase after labeling the enzyme with [alpha-32P]ATP to form the ligase-[32P]AMP adduct. The early eluting enzyme activity (0.25 M NaCl) contained a major 67-kDa-labeled protein, while the late eluting activity (0.48 M NaCl) contained two major labeled proteins of 90 and 78 kDa. Neutralization experiments with antiligase I antibodies indicated that the early and late eluting activity peaks were DNA ligase II and I, respectively. The three major ligase-[32P]AMP polypeptides (90, 78, and 67 kDa) were subsequently purified to near homogeneity by elution from preparative sodium dodecyl sulfate-polyacrylamide gels. All three polypeptides retained DNA ligase activities after gel elution and renaturation. To further reveal the relationship between these enzymes, partial digestion by V8-protease was performed. All three purified polypeptides gave rise to a common 22-kDa-labeled fragment for their AMP-binding domains, indicating that the catalytic sites of ligase I and II are quite similar, if not identical. Similar findings were obtained from the two-dimensional gel

  2. Association of HLA-DR3 with human immune response to Lol p I and Lol p II allergens in allergic subjects.

    Science.gov (United States)

    Freidhoff, L R; Ehrlich-Kautzky, E; Meyers, D A; Ansari, A A; Bias, W B; Marsh, D G

    1988-04-01

    Associations between HLA type and IgE or IgG antibody (Ab) responses to two well-characterized, antigenetically non-crossreactive components of Lolium perenne (rye grass) pollen extract, Lol p I (Rye I) and Lol p II (Rye II) were studied in two groups of skin-test positive (ST+) Caucasoid adults. By both nonparametric and parametric statistical methods, significant associations were found between Ab responses to both Lol I and Lol II and the possession of HLA-DR3. In view of the well-known associations of both DR3 and B8 (which are in linkage disequilibrium) with many autoimmune diseases, differences in anti-Lol I and anti-Lol II mean log[Ab] levels between B8+, DR3- vs B8-, DR3- subjects and B8+, DR3+ vs B8-, DR3+ subjects were investigated. No differences were found. Our data, along with recent RFLP and DNA sequence studies, suggest that an Ia molecule involved in immune recognition of a similar major Ia recognition site of both the Lol molecules may consist of a DR3 alpha-beta I pair. Abbreviations used: Ab: Antibody. HLA: Human leukocyte antigen. Lol p I, Lol I: Group I allergen from Lolium perenne pollen (Rye I). Lol p II, Lol II: Group II allergen from Lolium perenne pollen (Rye II). Mr: Relative molecular mass. Rx: Immunotherapy with grass pollen extracts. ST: Skin test.

  3. Safflor yellow B suppresses angiotensin II-mediated human umbilical vein cell injury via regulation of Bcl-2/p22phox expression

    International Nuclear Information System (INIS)

    Wang, Chaoyun; He, Yanhao; Yang, Ming; Sun, Hongliu; Zhang, Shuping; Wang, Chunhua

    2013-01-01

    Intracellular reactive oxygen species (ROS) are derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Angiotensin II (Ang II) can cause endothelial dysfunction by promoting intracellular ROS generation. Safflor yellow B (SYB) effectively inhibits ROS generation by upregulating Bcl-2 expression. In this study, we examined the effects of SYB on Ang II-induced injury to human umbilical vein endothelial cells (HUVECs), and elucidated the roles of NADPH oxidase and Bcl-2. We treated cultured HUVECs with Ang II, SYB, and Bcl-2 siRNA, and determined NADPH oxidase activity and ROS levels. Furthermore, cellular and mitochondrial physiological states were evaluated, and the expression levels of target proteins were analyzed. Ang II significantly enhanced intracellular ROS levels, caused mitochondrial membrane dysfunction, and decreased cell viability, leading to apoptosis. This was associated with increased expression of AT1R and p22 phox , increased NADPH oxidase activity, and an increased ratio of Bax/Bcl-2, leading to decreases in antioxidant enzyme activities, which were further strengthened after blocking Bcl-2. Compared to Ang II treatment alone, co-treatment with SYB significantly reversed HUVEC injury. Taken together, these results demonstrate that SYB could significantly protect endothelial cells from Ang II-induced cell damage, and that it does so by upregulating Bcl-2 expression and inhibiting ROS generation. - Highlights: • Angiotensin II depresses mitochondria physiological function. • Angiotensin II activates NADPH oxidase via up-regulating expresion of p22 phox . • Bcl-2 plays a pivotal role in improving mitochondria function and regulates ROS level. • Inhibitor of Bcl-2 promotes angiotensin II mediated HUVEC injury. • SYB attenuates angiotensin II mediated HUVEC injury via up regulating Bcl-2 expression

  4. Proportion of collagen type II in the extracellular matrix promotes the differentiation of human adipose-derived mesenchymal stem cells into nucleus pulposus cells.

    Science.gov (United States)

    Tao, Yiqing; Zhou, Xiaopeng; Liu, Dongyu; Li, Hao; Liang, Chengzhen; Li, Fangcai; Chen, Qixin

    2016-01-01

    During degeneration process, the catabolism of collagen type II and anabolism of collagen type I in nucleus pulposus (NP) may influence the bioactivity of transplanted cells. Human adipose-derived mesenchymal stem cells (hADMSCs) were cultured as a micromass or in a series of gradual proportion hydrogels of a mix of collagen types I and II. Cell proliferation and cytotoxicity were detected using CCK-8 and LDH assays respectively. The expression of differentiation-related genes and proteins, including SOX9, aggrecan, collagen type I, and collagen type II, was examined using RT-qPCR and Western blotting. Novel phenotypic genes were also detected by RT-qPCR and western blotting. Alcian blue and dimethylmethylene blue assays were used to investigate sulfate proteoglycan expression, and PI3K/AKT, MAPK/ERK, and Smad signaling pathways were examined by Western blotting. The results showed collagen hydrogels have good biocompatibility, and cell proliferation increased after collagen type II treatment. Expressions of SOX9, aggrecan, and collagen type II were increased in a collagen type II dependent manner. Sulfate proteoglycan synthesis increased in proportion to collagen type II concentration. Only hADMSCs highly expressed NP cell marker KRT19 in collagen type II culture. Additionally, phosphorylated Smad3, which is associated with phosphorylated ERK, was increased after collagen type II-stimulation. The concentration and type of collagen affect hADMSC differentiation into NP cells. Collagen type II significantly ameliorates hADMSC differentiation into NP cells and promotes extracellular matrix synthesis. Therefore, anabolism of collagen type I and catabolism of type II may attenuate the differentiation and biosynthesis of transplanted stem cells. © 2016 International Union of Biochemistry and Molecular Biology.

  5. Ultraviolet-induced DNA excision repair in human B and T lymphocytes. II

    International Nuclear Information System (INIS)

    Yew, F.F.-H.; Johnson, R.T.

    1979-01-01

    Despite their great sensitivity to ultraviolet light purified human B and T lymphocytes are capable of complete repair provided that the ultraviolet dose does not exceed 0.5 Jm -2 . Their capacity to repair, as measured by the restoration of DNA supercoiling in preparations of nucleoids, and their survival are significantly increased in the presence of deoxyribonucleosides. Certain agents which inhibit semi-conservative DNA synthesis (hydroxyurea, 1-β-D-arabino-furanosylcytosine (arafCyt) either stop or delay the repair process in lymphocytes. The effect of hydroxyurea is eventually overcome spontaneously, but changes in the sedimentation behaviour of ultraviolet-irradiated nucleoids caused by arafCyt can only be neutralized by addition of deoxycytidine. The effective inhibition of repair by arafCyt permits the detection of extremely small amounts of ultraviolet damage and also the estimation of when repair is complete. (Auth.)

  6. The Ecology of Human-Machine Systems II: Mediating 'Direct Perception' in Complex Work Domains

    DEFF Research Database (Denmark)

    Vicente, Kim J.; Rasmussen, Jens

    1990-01-01

    Recently, a new class of artifacts has appeared in our environment: complex, high-technology work domains. An important characteristic of such systems is that their goal-relevant properties cannot be directly observed by the unaided eye. As a result, interface design is a ubiquitous problem in th...... in the design of these work environments. Nevertheless, the problem is one that has yet to be addressed in an adequate manner. An analogy to human perceptual mechanisms suggests that a smart instrument approach to interface design is needed to supplant the rote instrument (single......-sensor-single-indicator) approach that has dominated to this point. Ecological interface design (ED) is a theoretical framework in the smart instrument vein that postulates a set of general, prescriptive principles for design. The goal of E D is twofold: first, to reveal the affordances of the work domain through the interface...

  7. Population and prehistory II: space-limited human populations in constant environments.

    Science.gov (United States)

    Puleston, Cedric O; Tuljapurkar, Shripad

    2008-09-01

    We present a population model to examine the forces that determined the quality and quantity of human life in early agricultural societies where cultivable area is limited. The model is driven by the non-linear and interdependent relationships between the age distribution of a population, its behavior and technology, and the nature of its environment. The common currency in the model is the production of food, on which age-specific rates of birth and death depend. There is a single non-trivial equilibrium population at which productivity balances caloric needs. One of the most powerful controls on equilibrium hunger level is fertility control. Gains against hunger are accompanied by decreases in population size. Increasing worker productivity does increase equilibrium population size but does not improve welfare at equilibrium. As a case study we apply the model to the population of a Polynesian valley before European contact.

  8. Functional brain mapping using H215O positron emission tomography (II): mapping of human working memory

    International Nuclear Information System (INIS)

    Lee, Jae Sung; Lee, Dong Soo; Lee, Sang Kun; Nam, Hyun Woo; Kim, Seok Ki; Park, Kwang Suk; Jeong, Jae Min; Chung, June Key; Lee, Myung Chul

    1998-01-01

    To localize and compare the neural basis of verbal and visual human working memory, we performed functional activation study using H 2 15 O PET. Repeated H 2 15 O PET scans with one control and three different activation tasks were performed on six right-handed normal volunteers. Each activation task was composed of 13 matching trials. On each trial, four targets, a fixation dot and a prove were presented sequentially and subject's tasks was to press a response button to indicate whether or not the prove was one of the previous targets. Short meaningful Korean words, simple drawings and monochromic pictures of human faces were used as matching objects for verbal or visual memory. All the images were spatially normalized and the differences between control and activation states were statistically analyzed using SPM96. Statistical analysis of verbal memory activation with short words showed activation in the left Broca's area, premotor cortex, cerebellum and right cingulate gyrus. In verbal memory with simple drawing, activation was shown in the larger regions including where activated with short words and left superior temporal cortex, basal ganglia, thalamus, prefrontal cortex, anterior portion of right superior temporal gyrus and right infero-lateral frontal cortex. On the other hand, the visual memory task activated predominantly right-sided structures, especially inferior frontal cortex, supplementary motor cortex and superior parietal cortex. The results are consistent with the hypothesis of the laterality and dissociation of the verbal and visual working memory from the invasive electrophysiological studies and emphasize the pivotal role of frontal cortex and cingulate gyrus in working memory system

  9. The intestinal absorption of dietary cholesterol by hypercholesterolemic (type II) and normocholesterolemic humans.

    Science.gov (United States)

    Connor, W E; Lin, D S

    1974-04-01

    The incomplete absorption of dietary cholesterol may represent an adaptive intestinal barrier that prevents hypercholesterolemia. To explore this mechanism, we compared cholesterol absorption in 15 normocholesterolemic and 6 hypercholesterolemic (type II) subjects fed background cholesterol-free formula diets with 40% of calories as fat. Each test meal consisted of a breakfast into which was incorporated scrambled egg yolk containing 300-500 mg of cholesterol and [4-(14)C]cholesterol (3-22 muCi), either naturally incorporated into the yolk cholesterol by previous isotope injection into the laying hen or added in peanut oil to the yolk of the test breakfast. In some instances [1alpha-(3)H]cholesterol was the radioactive marker. The radioactivity of the fecal neutral sterol fraction was determined in daily stool samples for the next 7 days to provide an estimate of unabsorbed dietary cholesterol. The amount of absorbed and reexcreted labeled cholesterol proved negligible. Most unabsorbed dietary cholesterol appeared in the stool on the second or third day after the meal, and 95% or more was recovered in the stool by 6 days. Plasma specific activity curves were usually maximal at 48 h. Normal subjects absorbed 44.5+/-9.3 (SD) of the administered cholesterol (range 25.9-60.3). Hypercholesterolemics absorbed the same percentage of cholesterol as normals: 47.6+/-12.6% (range 29.3-67.3). Absorption was similar whether the radiolabeled cholesterol was added to egg yolk or naturally incorporated in it (42.1+/-9.3 vs. 48.9+/-9.8%). Six normal subjects were fed a cholesterol-free formula for 4 wk, and then different amounts of cholesterol (110-610 mg/day) were added for another 4 wk. At the end of each period, single test meals containing either 110, 310, or 610 mg of cholesterol and [1alpha-(3)H]cholesterol were administered. Cholesterol absorption was 42.3+/-6.0% and 45.4+/-8.3% for the two dietary periods, respectively. The absolute cholesterol absorption was linearly

  10. [PHEMA/PEI]–Cu(II) based immobilized metal affinity chromatography cryogels: Application on the separation of IgG from human plasma

    Energy Technology Data Exchange (ETDEWEB)

    Bakhshpour, Monireh; Derazshamshir, Ali; Bereli, Nilay [Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara (Turkey); Elkak, Assem [Laboratory of “Valorisation des Ressources Naturelles et Produits de Santé (VRNPS)”, Doctoral School of Sciences and Technology, Lebanese University, Rafic Hariri University Campus, Hadath (Lebanon); Denizli, Adil, E-mail: denizli@hacettepe.edu [Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara (Turkey)

    2016-04-01

    The immobilized metal-affinity chromatography (IMAC) has gained significant interest as a widespread separation and purification tool for therapeutic proteins, nucleic acids and other biological molecules. The enormous potential of IMAC for proteins with natural surface exposed-histidine residues and for recombinant proteins with histidine clusters. Cryogels as monolithic materials have recently been proposed as promising chromatographic adsorbents for the separation of biomolecules in downstream processing. In the present study, IMAC cryogels have been synthesized and utilized for the adsorption and separation of immunoglobulin G (IgG) from IgG solution and whole human plasma. For this purpose, Cu(II)-ions were coupled to poly(hydroxyethyl methacrylate) PHEMA using poly(ethylene imine) (PEI) as the chelating ligand. In this study the cryogels formation optimized by the varied proportion of PEI from 1% to 15% along with different amounts of Cu (II) as chelating metal. The prepared cryogels were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The [PHEMA/PEI]–Cu(II) cryogels were assayed for their capability to bind the human IgG from aqueous solutions. The IMAC cryogels were found to have high affinity toward human IgG. The adsorption of human IgG was investigated onto the PHEMA/PEI cryogels with (10% PEI) and the concentration of Cu (II) varied as 10, 50, 100 and 150 mg/L. The separation of human IgG was achieved in one purification step at pH 7.4. The maximum adsorption capacity was observed at the [PHEMA/PEI]–Cu(II) (10% PEI) with 72.28 mg/g of human IgG. The purification efficiency and human IgG purity were investigated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). - Highlights: • Cu(II)-ions were coupled to PHEMA using PEI as the chelating ligand. • Cu(II) chelated [PHEMA/PEI] cryogels for IgG separation were produced. • Maximum IgG adsorption capacity

  11. [PHEMA/PEI]–Cu(II) based immobilized metal affinity chromatography cryogels: Application on the separation of IgG from human plasma

    International Nuclear Information System (INIS)

    Bakhshpour, Monireh; Derazshamshir, Ali; Bereli, Nilay; Elkak, Assem; Denizli, Adil

    2016-01-01

    The immobilized metal-affinity chromatography (IMAC) has gained significant interest as a widespread separation and purification tool for therapeutic proteins, nucleic acids and other biological molecules. The enormous potential of IMAC for proteins with natural surface exposed-histidine residues and for recombinant proteins with histidine clusters. Cryogels as monolithic materials have recently been proposed as promising chromatographic adsorbents for the separation of biomolecules in downstream processing. In the present study, IMAC cryogels have been synthesized and utilized for the adsorption and separation of immunoglobulin G (IgG) from IgG solution and whole human plasma. For this purpose, Cu(II)-ions were coupled to poly(hydroxyethyl methacrylate) PHEMA using poly(ethylene imine) (PEI) as the chelating ligand. In this study the cryogels formation optimized by the varied proportion of PEI from 1% to 15% along with different amounts of Cu (II) as chelating metal. The prepared cryogels were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The [PHEMA/PEI]–Cu(II) cryogels were assayed for their capability to bind the human IgG from aqueous solutions. The IMAC cryogels were found to have high affinity toward human IgG. The adsorption of human IgG was investigated onto the PHEMA/PEI cryogels with (10% PEI) and the concentration of Cu (II) varied as 10, 50, 100 and 150 mg/L. The separation of human IgG was achieved in one purification step at pH 7.4. The maximum adsorption capacity was observed at the [PHEMA/PEI]–Cu(II) (10% PEI) with 72.28 mg/g of human IgG. The purification efficiency and human IgG purity were investigated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). - Highlights: • Cu(II)-ions were coupled to PHEMA using PEI as the chelating ligand. • Cu(II) chelated [PHEMA/PEI] cryogels for IgG separation were produced. • Maximum IgG adsorption capacity

  12. Long-term effects of prenatal x-ray of human females. II. Growth and development.

    Science.gov (United States)

    Meyer, M B; Tonascia, J

    1981-09-01

    Experimental studies and studies of survivors of in-utero exposure to atomic bomb blasts have shown significant stunting of growth and mental retardation following these exposures. Central nervous system damage following very low doses of x-ray at around the time of birth has also been observed in experimental animals. This long term follow-up studies of 1458 human females exposed in utero to diagnostic x-rays and of 1458 matched unexposed controls studied in Baltimore, Maryland, included measurements of height, weight and school achievement. Women who had been exposed to x-rays in utero were significantly shorter in their mid-twenties than were their matched, unexposed controls, even after adjustment for other social and economic factors. However, additional follow-up revealed that mothers of exposed women were also shorter than the control mothers. Short stature appeared to be a selective factor for x-ray during pregnancy (mostly pelvimetry, 1947-1952). Mothers' and daughters' heights were similarly correctly among exposed and control mother-daughter pairs, suggesting that the height differences between exposed daughters and their controls were due to these selective factor rather than to any direct effect of radiation on growth. Exposed women reported poorer school achievement than control women. However, except for a higher proportion of exposed women leaving school because of pregnancy, these measurements were no longer significantly different when rates were simultaneously adjusted for socioeconomic differences between exposed and control women.

  13. Selective attention reduces physiological noise in the external ear canals of humans. II: Visual attention

    Science.gov (United States)

    Walsh, Kyle P.; Pasanen, Edward G.; McFadden, Dennis

    2014-01-01

    Human subjects performed in several behavioral conditions requiring, or not requiring, selective attention to visual stimuli. Specifically, the attentional task was to recognize strings of digits that had been presented visually. A nonlinear version of the stimulus-frequency otoacoustic emission (SFOAE), called the nSFOAE, was collected during the visual presentation of the digits. The segment of the physiological response discussed here occurred during brief silent periods immediately following the SFOAE-evoking stimuli. For all subjects tested, the physiological-noise magnitudes were substantially weaker (less noisy) during the tasks requiring the most visual attention. Effect sizes for the differences were >2.0. Our interpretation is that cortico-olivo influences adjusted the magnitude of efferent activation during the SFOAE-evoking stimulation depending upon the attention task in effect, and then that magnitude of efferent activation persisted throughout the silent period where it also modulated the physiological noise present. Because the results were highly similar to those obtained when the behavioral conditions involved auditory attention, similar mechanisms appear to operate both across modalities and within modalities. Supplementary measurements revealed that the efferent activation was spectrally global, as it was for auditory attention. PMID:24732070

  14. La carrera política y el capital político

    Directory of Open Access Journals (Sweden)

    Manuel Alcántara-Sáez

    2017-01-01

    Full Text Available Se trata de una propuesta de naturaleza teórica para el estudio de las carreras políticas desde la perspectiva de la existencia de tres momentos diferentes (entrada, desempeño y salida, en conformidad con el uso del capital político que gestionan los políticos. Se abordan teóricamente distintos patrones de capital político así como su impacto sobre las trayectorias políticas seguidas. El peso del tiempo transcurrido y los ingresos recibidos por la actividad política son igualmente considerados. Político es aquella persona que es elegida en un proceso electoral y/o que es nominada en un puesto de confianza por alguien elegido, también lo es quien tiene un cargo orgánico en una institución como un partido político. A ello debe sumarse recibir una remuneración por esa actividad.

  15. Charged-particle mutagenesis II. Mutagenic effects of high energy charged particles in normal human fibroblasts

    Science.gov (United States)

    Chen, D. J.; Tsuboi, K.; Nguyen, T.; Yang, T. C.

    1994-01-01

    The biological effects of high LET charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/micrometer to 975 KeV/micrometer with particle energy (on the cells) between 94-603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/micrometer. The inactivation cross-section (alpha i) and the action cross-section for mutant induction (alpha m) ranged from 2.2 to 92.0 micrometer2 and 0.09 to 5.56 x 10(-3) micrometer2, respectively. The maximum values were obtained by 56Fe with an LET of 200 keV/micrometer. The mutagenicity (alpha m/alpha i) ranged from 2.05 to 7.99 x 10(-5) with the maximum value at 150 keV/micrometer. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.

  16. Hepatic glycogen in humans. II. Gluconeogenetic formation after oral and intravenous glucose

    International Nuclear Information System (INIS)

    Radziuk, J.

    1989-01-01

    The amount of glycogen that is formed by gluconeogenetic pathways during glucose loading was quantitated in human subjects. Oral glucose loading was compared with its intravenous administration. Overnight-fasted subjects received a constant infusion or [3- 3 H]glucose and a marker for gluconeogenesis, [U- 14 C]lactate or sodium [ 14 C]bicarbonate [ 14 C]bicarbonate. An unlabeled glucose load was then administered. Postabsorptively, or after glucose infusion was terminated, a third tracer ([6- 3 H]glucose) infusion was initiated along with a three-step glucagon infusion. Without correcting for background stimulation of [ 14 C]glucose production or for dilution of 14 C with citric acid cycle carbon in the oxaloacetate pool, the amount of glycogen mobilized by the glucagon infusion that was produced by gluconeogenesis during oral glucose loading was 2.9 +/- 0.7 g calculated from [U- 14 C]-lactate incorporation and 7.4 +/- 1.3 g calculated using [ 14 C]bicarbonate as a gluconeogenetic marker. During intravenous glucose administration the latter measurement also yielded 7.2 +/- 1.1 g. When the two corrections above are applied, the respective quantities became 5.3 +/- 1.7 g for [U- 14 C]lactate as tracer and 14.7 +/- 4.3 and 13.9 +/- 3.6 g for oral and intravenous glucose with [ 14 C]bicarbonate as tracer (P less than 0.05, vs. [ 14 C]-lactate as tracer). When [2- 14 C]acetate was infused, the same amount of label was incorporated into mobilized glycogen regardless of which route of glucose administration was used. Comparison with previous data also suggests that 14 CO 2 is a potentially useful marker for the gluconeogenetic process in vivo

  17. Molecular imaging of the human pulmonary vascular endothelium in pulmonary hypertension: a phase II safety and proof of principle trial

    Energy Technology Data Exchange (ETDEWEB)

    Harel, Francois [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Nuclear Medicine, Montreal, Quebec (Canada); Langleben, David; Abikhzer, Gad [McGill University, Lady Davis Institute and Jewish General Hospital, Montreal, Quebec (Canada); Provencher, Steve; Guimond, Jean [Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec (Canada); Fournier, Alain; Letourneau, Myriam [INRS-Institut Armand-Frappier, Laval, Quebec (Canada); Finnerty, Vincent; Nguyen, Quang T.; Levac, Xavier [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Mansour, Asmaa; Guertin, Marie-Claude [Montreal Health Innovation Coordination Center, Montreal, QC (Canada); Dupuis, Jocelyn [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Medicine, Montreal, Quebec (Canada)

    2017-07-15

    The adrenomedullin receptor is densely expressed in the pulmonary vascular endothelium. PulmoBind, an adrenomedullin receptor ligand, was developed for molecular diagnosis of pulmonary vascular disease. We evaluated the safety of PulmoBind SPECT imaging and its capacity to detect pulmonary vascular disease associated with pulmonary hypertension (PH) in a human phase II study. Thirty patients with pulmonary arterial hypertension (PAH, n = 23) or chronic thromboembolic PH (CTEPH, n = 7) in WHO functional class II (n = 26) or III (n = 4) were compared to 15 healthy controls. Lung SPECT was performed after injection of 15 mCi {sup 99m}Tc-PulmoBind in supine position. Qualitative and semi-quantitative analyses of lung uptake were performed. Reproducibility of repeated testing was evaluated in controls after 1 month. PulmoBind injection was well tolerated without any serious adverse event. Imaging was markedly abnormal in PH with ∝50% of subjects showing moderate to severe heterogeneity of moderate to severe extent. The abnormalities were unevenly distributed between the right and left lungs as well as within each lung. Segmental defects compatible with pulmonary embolism were present in 7/7 subjects with CTEPH and in 2/23 subjects with PAH. There were no segmental defects in controls. The PulmoBind activity distribution index, a parameter indicative of heterogeneity, was elevated in PH (65% ± 28%) vs. controls (41% ± 13%, p = 0.0003). In the only subject with vasodilator-responsive idiopathic PAH, PulmoBind lung SPECT was completely normal. Repeated testing 1 month later in healthy controls was well tolerated and showed no significant variability of PulmoBind distribution. In this phase II study, molecular SPECT imaging of the pulmonary vascular endothelium using {sup 99m}Tc-PulmoBind was safe. PulmoBind showed potential to detect both pulmonary embolism and abnormalities indicative of pulmonary vascular disease in PAH. Phase III studies with this novel tracer and

  18. The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II

    DEFF Research Database (Denmark)

    Elmlund, Hans; Baraznenok, Vera; Lindahl, Martin

    2006-01-01

    CDK8 (cyclin-dependent kinase 8), along with CycC, Med12, and Med13, form a repressive module (the Cdk8 module) that prevents RNA polymerase II (pol II) interactions with Mediator. Here, we report that the ability of the Cdk8 module to prevent pol II interactions is independent of the Cdk8......-dependent kinase activity. We use electron microscopy and single-particle reconstruction to demonstrate that the Cdk8 module forms a distinct structural entity that binds to the head and middle region of Mediator, thereby sterically blocking interactions with pol II....

  19. RNA polymerase II transcriptional fidelity control and its functional interplay with DNA modifications

    Science.gov (United States)

    Xu, Liang; Wang, Wei; Chong, Jenny; Shin, Ji Hyun; Xu, Jun; Wang, Dong

    2016-01-01

    Accurate genetic information transfer is essential for life. As a key enzyme involved in the first step of gene expression, RNA polymerase II (Pol II) must maintain high transcriptional fidelity while it reads along DNA template and synthesizes RNA transcript in a stepwise manner during transcription elongation. DNA lesions or modifications may lead to significant changes in transcriptional fidelity or transcription elongation dynamics. In this review, we will summarize recent progress towards understanding the molecular basis of RNA Pol II transcriptional fidelity control and impacts of DNA lesions and modifications on Pol II transcription elongation. PMID:26392149

  20. Characterization of cDNA for human tripeptidyl peptidase II: The N-terminal part of the enzyme is similar to subtilisin

    International Nuclear Information System (INIS)

    Tomkinson, B.; Jonsson, A-K

    1991-01-01

    Tripeptidyl peptidase II is a high molecular weight serine exopeptidase, which has been purified from rat liver and human erythrocytes. Four clones, representing 4453 bp, or 90% of the mRNA of the human enzyme, have been isolated from two different cDNA libraries. One clone, designated A2, was obtained after screening a human B-lymphocyte cDNA library with a degenerated oligonucleotide mixture. The B-lymphocyte cDNA library, obtained from human fibroblasts, were rescreened with a 147 bp fragment from the 5' part of the A2 clone, whereby three different overlapping cDNA clones could be isolated. The deduced amino acid sequence, 1196 amino acid residues, corresponding to the longest open rading frame of the assembled nucleotide sequence, was compared to sequences of current databases. This revealed a 56% similarity between the bacterial enzyme subtilisin and the N-terminal part of tripeptidyl peptidase II. The enzyme was found to be represented by two different mRNAs of 4.2 and 5.0 kilobases, respectively, which probably result from the utilziation of two different polyadenylation sites. Futhermore, cDNA corresponding to both the N-terminal and C-terminal part of tripeptidyl peptidase II hybridized with genomic DNA from mouse, horse, calf, and hen, even under fairly high stringency conditions, indicating that tripeptidyl peptidase II is highly conserved

  1. Analyzing the 3D Structure of Human Carbonic Anhydrase II and Its Mutants Using Deep View and the Protein Data Bank

    Science.gov (United States)

    Ship, Noam J.; Zamble, Deborah B.

    2005-01-01

    The self directed study of a 3D image of a biomolecule stresses the complex nature of the intra- and intermolecular interactions that come together to define its structure. This is made up of a series of in vitro experiments with a wild-type and mutants forms of human carbonic anhydrase II (hCAII) that examine the structure function relationship…

  2. Low prevalence of human T-cell leukaemia virus-I and -II infection among drug users in Amsterdam, The Netherlands

    NARCIS (Netherlands)

    van den Hoek, J. A.; Al, E. J.; Huisman, J. G.; Goudsmit, J.; Coutinho, R. A.

    1991-01-01

    The prevalence of human T-cell leukaemia virus-I and -II infection was studied in a cohort of 346 intravenous and nonintravenous drug users in Amsterdam. Three participants (0.86%) had antibodies to HTLV-I by two commercially available HTLV-I enzyme immunoassays (EIA). Infection in these three

  3. Effects of recombinant human granulocyte colony-stimulating factor on leucopenia in zidovudine-treated patients with AIDS and AIDS related complex, a phase I/II study

    NARCIS (Netherlands)

    van der Wouw, P. A.; van Leeuwen, R.; van Oers, R. H.; Lange, J. M.; Danner, S. A.

    1991-01-01

    Twelve male patients, eight with the acquired immunodeficiency syndrome (AIDS) and four with AIDS related complex (ARC), who had zidovudine associated neutropenia (less than 1 x 10(9) neutrophils/l) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) in a phase I/II

  4. II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies.

    Science.gov (United States)

    Goudouris, Ekaterini Simões; Rego Silva, Almerinda Maria do; Ouricuri, Aluce Loureiro; Grumach, Anete Sevciovic; Condino-Neto, Antonio; Costa-Carvalho, Beatriz Tavares; Prando, Carolina Cardoso; Kokron, Cristina Maria; Vasconcelos, Dewton de Moraes; Tavares, Fabíola Scancetti; Silva Segundo, Gesmar Rodrigues; Barreto, Irma Cecília; Dorna, Mayra de Barros; Barros, Myrthes Anna; Forte, Wilma Carvalho Neves

    2017-01-01

    In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil. RESUMO Nos últimos anos, novas imunodeficiências primárias e defeitos genéticos têm sido descritos. Recentemente, produtos de imunoglobulina, com aprimoramento em sua composição e para uso por via subcutânea, tornaram-se disponíveis em nosso meio. Com o objetivo de orientar o médico no uso da imunoglobulina humana para o tratamento das imunodeficiências primárias, os membros do Grupo de Assessoria em Imunodeficiências da Associação Brasileira de Alergia e Imunologia produziram um documento que teve por base uma revisão narrativa da literatura e sua experiência profissional, atualizando o I Consenso Brasileiro publicado em 2010. Apresentam-se novos conhecimentos sobre indicações e eficácia do tratamento com imunoglobulina nas imunodeficiências primárias, aspectos relevantes sobre a produção, forma de utilização (vias de administração, farmacocinética, doses e intervalos), efeitos adversos (principais efeitos, prevenção, tratamento e notificação), monitorização do

  5. Relative frequency of Human T-cell Lymphotropic Virus I/II in HIV/AIDS patients

    Directory of Open Access Journals (Sweden)

    Mohsen Meidani

    2014-01-01

    Conclusion: In our survey, relative frequency of HTLV-I/II was 1.8% in HIV+ patients. This study reveals that relative frequency of HTLV-I/II in HIV positive patients is considerable but determining the need for screening of HTLV-I/II requires further investigation.

  6. Soil physical degradation by human activities in the zone II of the basin of Burgos, Tamaulipas, Mexico

    International Nuclear Information System (INIS)

    Arias Mino, F.; Espinosa Rmirez, M.; Andrade Limas, E.; Castro Meza, B.; Romero Diaz, A.

    2009-01-01

    The objective of this work was to characterize the physical degradation of the soil for antropic activities during the years 2007 and 2008 in the II zone of the Burgos Basin in Tamaulipas, Mexico. In this region, human action manifests itself due to activities such as agriculture, livestock and industry. The conventional farming, based mainly on the cultivation of sorghum, is characterized by great mechanization and tilling the soil which has contributed in large measure to aggravate erosion processes. There is also some logging, mainly for charcoal production and, recently, has joined the exploration and exploitation of natural gas. We used the methodology for Assessment of Soil Degradation (ASSOD) to identify, located and define the types of soil degradation within physiographic units. Results showed that nearly 74% of the study area presents some kind of degradation. The main process was water erosion, followed, by compaction and wind erosion. The main factors are essentially overgrazing and inadequate farming practices. Approximately 60% of the units evaluated presented a moderate level of degradation, but the speed of this process indicates that maintenance works are needed to reverse. (Author) 7 refs.

  7. Downregulation of Type II Diabetes Mellitus and Maturity Onset Diabetes of Young Pathways in Human Pancreatic Islets from Hyperglycemic Donors

    Directory of Open Access Journals (Sweden)

    Jalal Taneera

    2014-01-01

    Full Text Available Although several molecular pathways have been linked to type 2 diabetes (T2D pathogenesis, it is uncertain which pathway has the most implication on the disease. Changes in the expression of an entire pathway might be more important for disease pathogenesis than changes in the expression of individual genes. To identify the molecular alterations in T2D, DNA microarrays of human pancreatic islets from donors with hyperglycemia n=20 and normoglycemia n=58 were subjected to Gene Set Enrichment Analysis (GSEA. About 178 KEGG pathways were investigated for gene expression changes between hyperglycemic donors compared to normoglycemic. Pathway enrichment analysis showed that type II diabetes mellitus (T2DM and maturity onset diabetes of the young (MODY pathways are downregulated in hyperglycemic donors, while proteasome and spliceosome pathways are upregulated. The mean centroid of gene expression of T2DM and MODY pathways was shown to be associated positively with insulin secretion and negatively with HbA1c level. To conclude, downregulation of T2DM and MODY pathways is involved in islet function and might be involved in T2D. Also, the study demonstrates that gene expression profiles from pancreatic islets can reveal some of the biological processes related to regulation of glucose hemostats and diabetes pathogenesis.

  8. Excess Polθ functions in response to replicative stress in homologous recombination-proficient cancer cells

    Directory of Open Access Journals (Sweden)

    T. Goullet de Rugy

    2016-10-01

    Full Text Available DNA polymerase theta (Polθ is a specialized A-family DNA polymerase that functions in processes such as translesion synthesis (TLS, DNA double-strand break repair and DNA replication timing. Overexpression of POLQ, the gene encoding Polθ, is a prognostic marker for an adverse outcome in a wide range of human cancers. While increased Polθ dosage was recently suggested to promote survival of homologous recombination (HR-deficient cancer cells, it remains unclear whether POLQ overexpression could be also beneficial to HR-proficient cancer cells. By performing a short interfering (siRNA screen in which genes encoding druggable proteins were knocked down in Polθ-overexpressing cells as a means to uncover genetic vulnerabilities associated with POLQ overexpression, we could not identify genes that were essential for viability in Polθ-overexpressing cells in normal growth conditions. We also showed that, upon external DNA replication stress, Polθ expression promotes cell survival and limits genetic instability. Finally, we report that POLQ expression correlates with the expression of a set of HR genes in breast, lung and colorectal cancers. Collectively, our data suggest that Polθ upregulation, besides its importance for survival of HR-deficient cancer cells, may be crucial also for HR-proficient cells to better tolerate DNA replication stress, as part of a global gene deregulation response, including HR genes.

  9. Rapid Genome-wide Recruitment of RNA Polymerase II Drives Transcription, Splicing, and Translation Events during T Cell Responses

    Directory of Open Access Journals (Sweden)

    Kathrin Davari

    2017-04-01

    Full Text Available Summary: Activation of immune cells results in rapid functional changes, but how such fast changes are accomplished remains enigmatic. By combining time courses of 4sU-seq, RNA-seq, ribosome profiling (RP, and RNA polymerase II (RNA Pol II ChIP-seq during T cell activation, we illustrate genome-wide temporal dynamics for ∼10,000 genes. This approach reveals not only immediate-early and posttranscriptionally regulated genes but also coupled changes in transcription and translation for >90% of genes. Recruitment, rather than release of paused RNA Pol II, primarily mediates transcriptional changes. This coincides with a genome-wide temporary slowdown in cotranscriptional splicing, even for polyadenylated mRNAs that are localized at the chromatin. Subsequent splicing optimization correlates with increasing Ser-2 phosphorylation of the RNA Pol II carboxy-terminal domain (CTD and activation of the positive transcription elongation factor (pTEFb. Thus, rapid de novo recruitment of RNA Pol II dictates the course of events during T cell activation, particularly transcription, splicing, and consequently translation. : Davari et al. visualize global changes in RNA Pol II binding, transcription, splicing, and translation. T cells change their functional program by rapid de novo recruitment of RNA Pol II and coupled changes in transcription and translation. This coincides with fluctuations in RNA Pol II phosphorylation and a temporary reduction in cotranscriptional splicing. Keywords: RNA Pol II, cotranscriptional splicing, T cell activation, ribosome profiling, 4sU, H3K36, Ser-5 RNA Pol II, Ser-2 RNA Pol II, immune response, immediate-early genes

  10. Enterovirus 71 VP1 activates calmodulin-dependent protein kinase II and results in the rearrangement of vimentin in human astrocyte cells.

    Directory of Open Access Journals (Sweden)

    Cong Haolong

    Full Text Available Enterovirus 71 (EV71 is one of the main causative agents of foot, hand and mouth disease. Its infection usually causes severe central nervous system diseases and complications in infected infants and young children. In the present study, we demonstrated that EV71 infection caused the rearrangement of vimentin in human astrocytoma cells. The rearranged vimentin, together with various EV71 components, formed aggresomes-like structures in the perinuclear region. Electron microscopy and viral RNA labeling indicated that the aggresomes were virus replication sites since most of the EV71 particles and the newly synthesized viral RNA were concentrated here. Further analysis revealed that the vimentin in the virus factories was serine-82 phosphorylated. More importantly, EV71 VP1 protein is responsible for the activation of calmodulin-dependent protein kinase II (CaMK-II which phosphorylated the N-terminal domain of vimentin on serine 82. Phosphorylation of vimentin and the formation of aggresomes were required for the replication of EV71 since the latter was decreased markedly after phosphorylation was blocked by KN93, a CaMK-II inhibitor. Thus, as one of the consequences of CaMK-II activation, vimentin phosphorylation and rearrangement may support virus replication by playing a structural role for the formation of the replication factories. Collectively, this study identified the replication centers of EV71 in human astrocyte cells. This may help us understand the replication mechanism and pathogenesis of EV71 in human.

  11. Regulation of hypoxia-inducible factor-1α (HIF-1α expression by interleukin-1β (IL-1 β, insulin-like growth factors I (IGF-I and II (IGF-II in human osteoarthritic chondrocytes

    Directory of Open Access Journals (Sweden)

    Angelica Rossi Sartori-Cintra

    2012-01-01

    Full Text Available OBJECTIVE: Hypoxia-inducible factor 1 alpha regulates genes related to cellular survival under hypoxia. This factor is present in osteroarthritic chondrocytes, and cytokines, such as interleukin-1 beta, participate in the pathogenesis of osteoarthritis, thereby increasing the activities of proteolytic enzymes, such as matrix metalloproteinases, and accelerating cartilage destruction. We hypothesize that Hypoxia Inducible Factor-1 alpha (HIF-1α can regulate cytokines (catabolic action and/or growth factors (anabolic action in osteoarthritis. The purpose of this study was to investigate the modulation of HIF-1α in human osteoarthritic chondrocytes by interleukin-1 beta (IL-1β and insulin-like growth factors I (IGF-I and II (IGF-II and to determine the involvement of the phosphatidylinositol-3kinase (PI-3K pathway in this process. METHODS: Human osteroarthritic chondrocytes were stimulated with IL-1β, IGF-I and IGF-II and LY294002, a specific inhibitor of PI-3K. Nuclear protein levels and gene expression were analyzed by western blot and quantitative reverse transcription-polymerase chain reaction analyses, respectively. RESULTS: HIF-1α expression was upregulated by IL-1β at the protein level but not at the gene level. IGF-I treatment resulted in increases in both the protein and mRNA levels of HIF-1α , whereas IGF-II had no effect on its expression. However, all of these stimuli exploited the PI-3K pathway. CONCLUSION: IL-1β upregulated the levels of HIF-1α protein post-transcriptionally, whereas IGF-I increased HIF-1α at the transcript level. In contrast, IGF-II did not affect the protein or gene expression levels of HIF-1α . Furthermore, all of the tested stimuli exploited the PI-3K pathway to some degree. Based on these findings, we are able to suggest that Hypoxia inducible Factor-1 exhibits protective activity in chondrocytes during osteoarthritis.

  12. Agendamento de Políticas Públicas

    Directory of Open Access Journals (Sweden)

    Rosane Rosa

    2011-07-01

    Full Text Available Aborda-se o conceito de advocacy e contra-agendamento como uma forma de a Sociedade Civil incluir suas causas na mídia, objetivando a tematização e a possibilidade de transformar-se em política pública. Analisa-se a reportagem “Uma conquista longe das ruas”; resultado de um agendamento compartilhado e que, em muitos aspectos, serve de referência para cobertura de políticas públicas sociais.

  13. A visibilidade política na série The Crown

    Directory of Open Access Journals (Sweden)

    Giovana dos Passos Colling

    2018-02-01

    Full Text Available O presente trabalho tem por objetivo compreender como se configura a visibilidade política na trama da série The Crown, produzida pela Netflix, por meio da análise dos três primeiros episódios. A partir do enredo da série, que conta a história da família real britânica na época em que a Raínha Elizabeth II assume o trono e suas novas responsabilidades políticas, é possível perceber e analisar as relações de poder entre a política, a sociedade e a mídia, além de temáticas como imagem pública, escândalo político, relações políticas entre países e discurso midiático. A análise de conteúdo se dá a partir dos autores Gomes, Thompson e Weber. Assim, torna-se perceptível a indissociabilidade entre a mídia, a sociedade e a política para a manutenção de um governo estável, que se utilizando da visibilidade midiática de maneira favorável, estabelece uma comunicação eficiente e uma imagem pública forte e positiva.

  14. Characterization of Mycobacterium smegmatis PolD2 and PolD1 as RNA/DNA polymerases homologous to the POL domain of bacterial DNA ligase D.

    Science.gov (United States)

    Zhu, Hui; Bhattarai, Hitesh; Yan, Han-Guang; Shuman, Stewart; Glickman, Michael S

    2012-12-21

    Mycobacteria exploit nonhomologous end-joining (NHEJ) to repair DNA double-strand breaks. The core NHEJ machinery comprises the homodimeric DNA end-binding protein Ku and DNA ligase D (LigD), a modular enzyme composed of a C-terminal ATP-dependent ligase domain (LIG), a central 3'-phosphoesterase domain (PE), and an N-terminal polymerase domain (POL). LigD POL is proficient at adding templated and nontemplated deoxynucleotides and ribonucleotides to DNA ends in vitro and is the catalyst in vivo of unfaithful NHEJ events involving nontemplated single-nucleotide additions to blunt DSB ends. Here, we identify two mycobacterial proteins, PolD1 and PolD2, as stand-alone homologues of the LigD POL domain. Biochemical characterization of PolD1 and PolD2 shows that they resemble LigD POL in their monomeric quaternary structures, their ability to add templated and nontemplated nucleotides to primer-templates and blunt ends, and their preference for rNTPs versus dNTPs. Deletion of polD1, polD2, or both from a Mycobacterium smegmatis strain carrying an inactivating mutation in LigD POL failed to reveal a role for PolD1 or PolD2 in templated nucleotide additions during NHEJ of 5'-overhang DSBs or in clastogen resistance. Whereas our results document the existence and characteristics of new stand-alone members of the LigD POL family of RNA/DNA polymerases, they imply that other polymerases can perform fill-in synthesis during mycobacterial NHEJ.

  15. MHC class II molecules deliver costimulatory signals in human T cells through a functional linkage with IL-2-receptors

    DEFF Research Database (Denmark)

    Odum, Niels; Kanner, S B; Ledbetter, J A

    1993-01-01

    MHC class II-positive T cells are found in tissues involved in autoimmune and infectious disorders. Because stimulation of class II molecules by mAb or bacterial superantigens induces protein tyrosine phosphorylation through activation of PTK3 in T cells, we hypothesized that class II signals play...... tyrosine phosphorylation of specific substrates including PLC-gamma 1. Combined stimulation of IL-2R and class II molecules had an additive effect on tyrosine phosphorylation. Pretreatment of T cells with a protein tyrosine kinase inhibitor, herbimycin A, inhibited IL-2 and class II-induced proliferation...... a regulatory function in T cell activation. Here, we show that cross-linking HLA-DR and -DP but not -DQ molecules by immobilized mAb enhanced proliferative T cell responses to IL-2. In contrast, class II stimulation had no effect on IL-4-induced proliferation. The costimulatory effect was most pronounced...

  16. Ingeniero, político, economista, inventor

    Directory of Open Access Journals (Sweden)

    Jimena Montaña Cuéllar

    2001-01-01

    Full Text Available Técnica y utopía. Biografía intelectual y política de Alejandro López, 1876-1940. Alberto Mayor Mora. Fondo Editorial Universidad Eafit, colección Cielos de Arena, Medellín, 2001, 621 págs., il.

  17. El marketing político

    Directory of Open Access Journals (Sweden)

    Alvaro H. Cifuentes G.

    2015-04-01

    Full Text Available RESUMEN Si un candidato desea ser elegido, las técnicas de marketing aplicadas a la política, le son imprescindibles. El marketing político (Politing es el análisis  metódico de los diferentes segmentos que integran el ámbito político de una sociedad y de los factores que puedan modificarlos. Se aplican al candidato, a los votantes, al análisis de la publicidad política, a los simpatizantes, a desconocedores  del partido y a los indecisos. Los candidatos colombianos lo están aplicando, y compañías nuestras exportan servicios  de asesoría de países suramericanos.Promocionar  un candidato implica estructurar una compañía tal como una empresa, aplicando técnicas de ventas, de fijación de cuotas y de planeación estratégica.

  18. Tricarbonyldichlororuthenium (II) dimer (CORM2) activates non-selective cation current in human endothelial cells independently of carbon monoxide releasing.

    Science.gov (United States)

    Dong, De-Li; Chen, Chang; Huang, Wei; Chen, Yan; Zhang, Xiao-Lan; Li, Zhe; Li, Yue; Yang, Bao-Feng

    2008-08-20

    Tricarbonyldichlororuthenium (II) dimer (CORM2) has been developed as carbon monoxide (CO) donor. We found that CORM2 activated a type of specific current which was distinct from the big-conductance Ca(2+)-activated K(+) current activated by CO in human umbilical vein endothelial cells (HUVECs). So the aim of the present study was to characterize the CORM2-induced current and to access the relation with CO releasing. CORM2 (100 microM) activated a kind of bi-directional current in HUVECs when the ramp protocol (holding potential 0 mV, from -120 mV to +120 mV) was applied. The current was not blocked by apamin, TRAM-34 and iberiotoxin, the small, intermediate and big-conductance Ca(2+) -activated K(+) channel blockers, and it was not sensitive to the pipette solution chelated with EGTA. CORM2 still activated the current when the chloride in the pipette solution was substituted by equal mol gluconic acid. Substitution of the sodium in the bath with choline significantly reduced the current activated by CORM2. The current was regarded as the non-selective cation current. The current showed slightly inward rectifier property and was not sensitive to Gd(3+) (100 microM), La(3+) (10 microM) or 2-aminoethoxydiphenyl borate (100 microM). CO (10 microM), CORM3 (100, 200 microM) and RuCl(3) (100 microM) were used as controls and showed no effect of the current activation. In conclusion, CORM2 activated the non-selective cation current in HUVECs independently of its CO releasing.

  19. Articular cartilage repair with recombinant human type II collagen/polylactide scaffold in a preliminary porcine study.

    Science.gov (United States)

    Muhonen, Virpi; Salonius, Eve; Haaparanta, Anne-Marie; Järvinen, Elina; Paatela, Teemu; Meller, Anna; Hannula, Markus; Björkman, Mimmi; Pyhältö, Tuomo; Ellä, Ville; Vasara, Anna; Töyräs, Juha; Kellomäki, Minna; Kiviranta, Ilkka

    2016-05-01

    The purpose of this study was to investigate the potential of a novel recombinant human type II collagen/polylactide scaffold (rhCo-PLA) in the repair of full-thickness cartilage lesions with autologous chondrocyte implantation technique (ACI). The forming repair tissue was compared to spontaneous healing (spontaneous) and repair with a commercial porcine type I/III collagen membrane (pCo). Domestic pigs (4-month-old, n = 20) were randomized into three study groups and a circular full-thickness chondral lesion with a diameter of 8 mm was created in the right medial femoral condyle. After 3 weeks, the chondral lesions were repaired with either rhCo-PLA or pCo together with autologous chondrocytes, or the lesion was only debrided and left untreated for spontaneous repair. The repair tissue was evaluated 4 months after the second operation. Hyaline cartilage formed most frequently in the rhCo-PLA treatment group. Biomechanically, there was a trend that both treatment groups resulted in better repair tissue than spontaneous healing. Adverse subchondral bone reactions developed less frequently in the spontaneous group (40%) and the rhCo-PLA treated group (50%) than in the pCo control group (100%). However, no statistically significant differences were found between the groups. The novel rhCo-PLA biomaterial showed promising results in this proof-of-concept study, but further studies will be needed in order to determine its effectiveness in articular cartilage repair. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:745-753, 2016. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  20. Trans- and cis-2-phenylindole platinum(II) complexes as cytotoxic agents against human breast adenocarcinoma cell lines

    Science.gov (United States)

    Tomé, Maria; López, Concepción; González, Asensio; Ozay, Bahadir; Quirante, Josefina; Font-Bardía, Mercè; Calvet, Teresa; Calvis, Carme; Messeguer, Ramon; Baldomá, Laura; Badía, Josefa

    2013-09-01

    The synthesis and characterization of the new 2-phenylindole derivative: C8H3N-2-C6H5-3NOMe-5OMe (3c) and the trans- and cis-isomers of [Pt(3c)Cl2(DMSO)] complexes (4c and 5c, respectively) are described. The crystal structures of 4c·CH2Cl2 and 5c confirm: (a) the existence of a Pt-Nindole bond, (b) the relative arrangement of the Cl- ligands [trans- (in 4c) or cis- (in 5c)] and (c) the anti-(E) configuration of the oxime. The cytotoxic assessment of C8H3N-2-(C6H4-4‧R1)-3NOMe-5R2 [with R1 = R2 = H (3a); R1 = Cl, R2 = H (3b) and R1 = H, R2 = OMe (3c)] and the geometrical isomers of [Pt(L)Cl2(DMSO)] with L = 3a-3c [trans- (4a-4c) and cis- (5a-5c), respectively] against human breast adenocarcinoma cell lines (MDA-MB231 and MCF-7) is also reported and reveals that all the platinum(II) complexes (except 4a) are more cytotoxic than cisplatin in front of the MCF7 cell line. Electrophoretic DNA migration studies of the synthesized compounds in the absence and in the presence of topoisomerase-I have been performed, in order to get further insights into their mechanism of action.

  1. Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy

    NARCIS (Netherlands)

    Hoffmann, S.; Krause, T.; van Geel, P. P.; Willenbrock, R.; Pagel, I.; Pinto, Y. M.; Buikema, H.; van Gilst, W. H.; Lindschau, C.; Paul, M.; Inagami, T.; Ganten, D.; Urata, H.

    2001-01-01

    Angiotensin II is known to stimulate cardiac hypertrophy and contractility. Most angiotensin II effects are mediated via membrane bound AT1 receptors. However, the role of myocardial AT1 receptors in cardiac hypertrophy and contractility is still rarely defined. To address the hypothesis that

  2. Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy

    NARCIS (Netherlands)

    Hoffmann, S; van Geel, PP; Willenbrock, R; Pagel, [No Value; Pinto, YM; Buikema, H; van Gilst, WH; Lindschau, C; Paul, M; Inagami, T; Ganten, D; Urata, H

    2001-01-01

    Angiotensin II is known to stimulate cardiac hypertrophy and contractility. Most angiotensin II effects are mediated via membrane bound AT(1) receptors. However, the role of myocardial AT(1) receptors in cardiac hypertrophy and contractility is still rarely defined. To address the hypothesis that

  3. Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Hougaard, S; Nørgaard, P; Abrahamsen, N

    1999-01-01

    Transforming growth factor beta (TGF-beta) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-beta due to lack of type II receptor (RII) has been described in some cancer types including small cell lung...

  4. Blogs, artefactos y política

    Directory of Open Access Journals (Sweden)

    María Belén Albornoz

    2010-05-01

    Full Text Available Este artículo problematiza la acepción de lo público en el espacio virtual que surge en la blogosfera política ecuatoriana en el contexto de la Asamblea Nacional Constituyente. A partir del análisis de la extensión de la política a los lugares virtuales, se aborda la blogosfera como proyecto político y la tecnología como formas de ordenamiento del mundo que la sociedad estabiliza. Se considera a la blogosfera política un espacio público regulado con la capacidad de ordenar y clasificar el mundo virtual por medio de dispositivos sociales, políticos y tecnológicos. Finalmente se propone el estudio del nuevo espacio público virtual desde un enfoque tecno-social que dé cuenta del entorno virtual como espacio formador de conductas.This article problematizes the acceptance of the public in the virtual space emerging in the Ecuadorian political blogosphere, in the context of the National Constitutional Assembly. Beginning with an analysis of the spread of politics to virtual spaces, the blogosphere is approached as a political project, and technology as ways of ordering the world that society stabilizes. The political blogosphere is taken to be a regulated public space with the ability to order and classify the virtual world by means of social, political and technological tools. Finally, the study of this new virtual public space from a techno-social focus is proposed, taking into account virtual surroundings as a space in which conducts are formed.

  5. SLIM-MAUD: an approach to assessing human error probabilities using structured expert judgment. Volume II. Detailed analysis of the technical issues

    International Nuclear Information System (INIS)

    Embrey, D.E.; Humphreys, P.; Rosa, E.A.; Kirwan, B.; Rea, K.

    1984-07-01

    This two-volume report presents the procedures and analyses performed in developing an approach for structuring expert judgments to estimate human error probabilities. Volume I presents an overview of work performed in developing the approach: SLIM-MAUD (Success Likelihood Index Methodology, implemented through the use of an interactive computer program called MAUD-Multi-Attribute Utility Decomposition). Volume II provides a more detailed analysis of the technical issues underlying the approach

  6. Type II cGMP‑dependent protein kinase inhibits the migration, invasion and proliferation of several types of human cancer cells.

    Science.gov (United States)

    Wu, Min; Wu, Yan; Qian, Hai; Tao, Yan; Pang, Ji; Wang, Ying; Chen, Yongchang

    2017-10-01

    Previous studies have indicated that type II cyclic guanosine monophosphate (cGMP)‑dependent protein kinase (PKG II) could inhibit the proliferation and migration of gastric cancer cells. However, the effects of PKG II on the biological functions of other types of cancer cells remain to be elucidated. Therefore, the aim of the present study was to investigate the effects of PKG II on cancer cells derived from various types of human tissues, including A549 lung, HepG2 hepatic, OS‑RC‑2 renal, SW480 colon cancer cells and U251 glioma cells. Cancer cells were infected with adenoviral constructs coding PKG II (Ad‑PKG II) to up‑regulate PKG II expression, and treated with 8‑(4‑chlorophenylthio) (8‑pCPT)‑cGMP to activate the kinase. A Cell Counting kit 8 assay was used to detect cell proliferation. Cell migration was measured using a Transwell assay, whereas a terminal deoxynucleotidyl transferase 2'‑deoxyuridine, 5'‑triphosphate nick‑end labeling assay was used to detect cell apoptosis. A pull‑down assay was used to investigate the activation of Ras‑related C3 botulinum toxin substrate (Rac) 1 and western blotting was used to detect the expression of proteins of interest. The present results demonstrated that EGF (100 ng/ml, 24 h) promoted the proliferation and migration of cancer cells, and it suppressed their apoptosis. In addition, treatment with EGF enhanced the activation of Rac1, and up‑regulated the protein expression of proliferating cell nuclear antigen, matrix metalloproteinase (MMP)2, MMP7 and B‑cell lymphoma (Bcl)‑2, whereas it down‑regulated the expression of Bcl‑2‑associated X protein. Transfection of cancer cells with Ad‑PKG II, and PKG II activation with 8‑pCPT‑cGMP, was identified to counteract the effects triggered by EGF. The present results suggested that PKG II may exert inhibitory effects on the proliferation and migration of various types of cancer cells.

  7. Observatorio de Política Internacional I. COLOMBIA - Colombia. Crónica de un proceso de paz fracasado

    OpenAIRE

    Neira Fernández, Enrique

    2007-01-01

    Observatorio de Política Internacional I. COLOMBIA (Neira Fernández, Enrique) RECIENTES Año 2008 Colombia. Cerca el fin del paramilitarismo Colombia. Cerca el fin de las Farc Colombia. Conflicto armado y desarrollo humano Colombia. Política exterior Colombia. Inicia el 2008 con buen pie Año 2007 Colombia. Tras las pasadas elecciones Colombia. El espectro de las próximas elecciones Colombia. La garrocha de Uribe Colombia. III Parapolíticos Colombia. II...

  8. Observatorio de Política Internacional I. COLOMBIA - El proceso de paz en sala de emergencia

    OpenAIRE

    Neira Fernández, Enrique

    2007-01-01

    Observatorio de Política Internacional I. COLOMBIA (Neira Fernández, Enrique) RECIENTES Año 2008 Colombia. Cerca el fin del paramilitarismo Colombia. Cerca el fin de las Farc Colombia. Conflicto armado y desarrollo humano Colombia. Política exterior Colombia. Inicia el 2008 con buen pie Año 2007 Colombia. Tras las pasadas elecciones Colombia. El espectro de las próximas elecciones Colombia. La garrocha de Uribe Colombia. III Parapolíticos Colombia. II...

  9. Cuando todo es político, ¿qué es la política?: una acotación empírica desde el post-humanismo Cuando todo es político, ¿qué es la política?: una acotación empírica desde el post-humanismo

    Directory of Open Access Journals (Sweden)

    Fernando Calonge Reíllo

    2009-04-01

    Full Text Available Este artículo intenta contribuir a resolver una de las más marcadas deficiencias que se atribuyen al paradigma post-humanista. En la medida en que desde dicho paradigma se señala que la ontología es política, se dificulta al mismo tiempo la comprensión de un sentido particular y específico de política. Desde esta visión, todo es político y, en consecuencia, nada es político. En el artículo reviso algunas de las soluciones que se han aportado para solventar esta carencia y añado las limitaciones que presentan. Buscando una vía para evitar la acusación, ofrezco una lectura post-humanista de las migraciones, para el caso concreto de las mujeres inmigrantes en la Comunidad de Madrid.Apartir de esa lectura, planteo la interrogación sobre qué constituyó, en concreto, la especificidad de las mujeres que migraron por razones políticas. A raíz de esta elucidación induzco unos mínimos criterios para caracterizar a la ‘migración política’, que la diferencie de otros tipos de migraciones. Desde esta elucidación realizo una extrapolación al campo más general de la política para el post-humanismo. Habiendo elucidado el hecho político de las migraciones políticas, intento establecer, dentro del paradigma post-humanista, qué constituye finalmente una noción específica y concreta sobre lo político que subsane la crítica de partida sobre la falta de especificidad de la política para el post-humanismo.In this article I will try to solve one of the most acute deficiencies in the post-humanist paradigm. As it is known, in this paradigm it is argued that ontology is political, therefore it has to be concluded that everything is political. In that case, post-humanism is accused of lacking a specific sense for the term ‘politics’. In the article, I review some of the solutions that have been proposed to give a more specific sense of politics and I include the reasons why such solutions are inadequate. Searching for a way to

  10. cobalt (ii), nickel (ii)

    African Journals Online (AJOL)

    DR. AMINU

    Department of Chemistry Bayero University, P. M. B. 3011, Kano, Nigeria. E-mail: hnuhu2000@yahoo.com. ABSTRACT. The manganese (II), cobalt (II), nickel (II) and .... water and common organic solvents, but are readily soluble in acetone. The molar conductance measurement [Table 3] of the complex compounds in.

  11. Políticas activas en las prestaciones por desempleo

    OpenAIRE

    Gil Jiménez, Javier

    2016-01-01

    El presente trabajo explica el tema de las políticas activas y políticas activas en las prestaciones por desempleo, tanto a nivel nacional como internacional. Para explicarlo se definen las políticas activas y sus funciones, tanto de formación, orientación y reinserción laboral. También se hace mención a las reformas llevadas a cabo en las diferentes políticas y el surgimiento de nuevos programas como función de políticas activas encaminadas a la reinserción laboral. Departamento de Derech...

  12. Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II

    NARCIS (Netherlands)

    A.G.A. Bijvoet (Agnes); A.J.J. Reuser (Arnold); H. van Hirtum (Hans); M.A. Kroos (Marian); E.H. van de Kamp; O. Schoneveld; P. Visser (Pim); J.P. Brakenhoff (Just); M. Weggeman (Miranda); E.J.J.M. van Corven (Emiel); A.T. van der Ploeg (Ans)

    1999-01-01

    textabstractPompe's disease or glycogen storage disease type II (GSDII) belongs to the family of inherited lysosomal storage diseases. The underlying deficiency of acid alpha-glucosidase leads in different degrees of severity to glycogen storage in heart, skeletal

  13. Clustered epitopes within the Gag-Pol fusion protein DNA vaccine enhance immune responses and protection against challenge with recombinant vaccinia viruses expressing HIV-1 Gag and Pol antigens

    International Nuclear Information System (INIS)

    Bolesta, Elizabeth; Gzyl, Jaroslaw; Wierzbicki, Andrzej; Kmieciak, Dariusz; Kowalczyk, Aleksandra; Kaneko, Yutaro; Srinivasan, Alagarsamy; Kozbor, Danuta

    2005-01-01

    We have generated a codon-optimized hGagp17p24-Polp51 plasmid DNA expressing the human immunodeficiency virus type 1 (HIV-1) Gag-Pol fusion protein that consists of clusters of highly conserved cytotoxic T lymphocyte (CTL) epitopes presented by multiple MHC class I alleles. In the hGagp17p24-Polp51 construct, the ribosomal frameshift site had been deleted together with the potentially immunosuppressive Gag nucleocapsid (p15) as well as Pol protease (p10) and integrase (p31). Analyses of the magnitude and breadth of cellular responses demonstrated that immunization of HLA-A2/K b transgenic mice with the hGagp17p24-Polp51 construct induced 2- to 5-fold higher CD8 + T-cell responses to Gag p17-, p24-, and Pol reverse transcriptase (RT)-specific CTL epitopes than the full-length hGag-PolΔFsΔPr counterpart. The increases were correlated with higher protection against challenge with recombinant vaccinia viruses (rVVs) expressing gag and pol gene products. Consistent with the profile of Gag- and Pol-specific CD8 + T cell responses, an elevated level of type 1 cytokine production was noted in p24- and RT-stimulated splenocyte cultures established from hGagp17p24-Polp51-immunized mice compared to responses induced with the hGag-PolΔFsΔPr vaccine. Sera of mice immunized with the hGagp17p24-Polp51 vaccine also exhibited an increased titer of p24- and RT-specific IgG2 antibody responses. The results from our studies provide insights into approaches for boosting the breadth of Gag- and Pol-specific immune responses

  14. Human leukocyte antigen class I and II alleles and cervical adenocarcinoma: a pooled analysis of two epidemiologic studies

    Directory of Open Access Journals (Sweden)

    Mahboobeh eSafaeian

    2014-06-01

    Full Text Available Associations between human leukocyte antigens (HLA alleles and cervical cancer are largely representative of squamous cell carcinoma (SCC, the major histologic subtype. We evaluated the association between HLA class I (A, B, and C and class II (DRB1 and DQB1 loci and risk of cervical adenocarcinoma (ADC, a less common but aggressive histologic subtype.We pooled data from the Eastern and Western US cervical cancer studies, and evaluated the association between individual alleles and allele combinations and ADC (n=630 ADC; n=775 controls. Risk estimates were calculated for 11 a priori (based on known associations with cervical cancer regardless of histologic type and 38 non a priori common alleles, as odds ratios (OR and 95% confidence intervals (CI, adjusted for age and study. In exploratory analysis, we compared the risk associations between subgroups with HPV16 or HPV18 DNA in ADC tumor tissues in the Western US study cases and controls. Three of the a priori alleles were significantly associated with decreased risk of ADC (DRB1*13:01 (OR=0.61; 95%CI:0.41-0.93, DRB1*13:02 (OR=0.49; 95%CI:0.31-0.77, and DQB1*06:03 (OR=0.64; 95%CI:0.42-0.95; one was associated with increased risk (B*07:02(OR=1.39; 95%CI:1.07-1.79. Among alleles not previously reported, DQB1*06:04 (OR=0.46; 95%CI: 0.27-0.78 was associated with decreased risk of ADC and C*07:02 (OR=1.41; 95%CI:1.09-1.81 was associated with increased risk. We did not observe a difference by histologic subtype. ADC was most strongly associated with increased risk with B*07:02/C*07:02 alleles (OR=1.33; 95%CI:1.01-1.76 and decreased risk with DRB1*13:02/DQB1*06:04 (OR=0.41; 95%CI:0.21-0.80. Results suggest that HLA allele associations with cervical ADC are similar to those for cervical SCC. An intriguing finding was the difference in risk associated with several alleles restricted to HPV16 or HPV18 related tumors, consistent with the hypothesis that HLA recognition is HPV type specific.

  15. Amor y política.

    OpenAIRE

    Hernando Bernal.

    1998-01-01

    Este trabajo pretende hacer una serie de consideraciones que apuntan sobre todo a extraer una definición de lo que es «la política» para el psicoanálisis a partir de una observación que hace Jacques Alain Miller en su texto Lógicas de la vida amorosa sobre cómo Freud introduce una «teoría política» a partir de su texto Psicología de las masas y análisis del yo.En dicho texto Freud hace ver el poder ordenador y apaciguador del amor) significante amo) en la medida en que una masa no es más que ...

  16. Hans Kelsen: pensador político

    Directory of Open Access Journals (Sweden)

    Sara Lagi

    2011-01-01

    Full Text Available Hasta la publicación de Sobre la esencia y el valor de la democracia, Hans Kelsen era solo conocido como experto en derecho público. El valor de este artículo de Lagi radica en rescatar de la obra kelseniana un aspecto casi por completo olvidado por la crítica, a saber, sus análisis sobre el significado y las características de la democracia parlamentaria en los Estados modernos. Se aborda la cuestión no solo desde el debate teórico sino también desde su contexto histórico¿político. La teoría política de Kelsen es considerada una parte integral de su doctrina central, presentada en Teoría pura del derecho, su obra más conspicua. Un análisis del trabajo sobre la esencia y el valor de la democracia nos restituye la imagen de un Kelsen como original pensador político. Se analizan las dos ediciones de Sobre la esencia y el valor de la democracia (1920¿1929 con estos propósitos: comprender por qué decidió dedicarse a la teoría de la democracia un teórico que rigurosamente defendió la separación de la esfera jurídica respecto de la historia, la filosofía y la política; y por qué no se limitó a explicar la esencia de la democracia sino que decidió concentrarse en clarificar qué se entiende por valor de la democracia.

  17. Química general II

    OpenAIRE

    Olba Torrent, Amparo

    2018-01-01

    El document forma part dels materials docents programats mitjançant l'ajut del Servei de Política Lingüística de la Universitat de València Temes de l'assignatura: Química general II del primer curs del Grau de Química Topics of the course: General Chemistry II in the first year of the Degree in Chemistry

  18. Coordination of different ligands to copper(II) and cobalt(III) metal centers enhances Zika virus and dengue virus loads in both arthropod cells and human keratinocytes.

    Science.gov (United States)

    Dutta, Shovan; Celestine, Michael J; Khanal, Supreet; Huddleston, Alexis; Simms, Colin; Arca, Jessa Faye; Mitra, Amlan; Heller, Loree; Kraj, Piotr J; Ledizet, Michel; Anderson, John F; Neelakanta, Girish; Holder, Alvin A; Sultana, Hameeda

    2018-01-01

    Trace elements such as copper and cobalt have been associated with virus-host interactions. However, studies to show the effect of conjugation of copper(II) or cobalt(III) metal centers to thiosemicarbazone ligand(s) derived from either food additives or mosquito repellent such as 2-acetylethiazole or citral, respectively, on Zika virus (ZIKV) or dengue virus (serotype 2; DENV2) infections have not been explored. In this study, we show that four compounds comprising of thiosemicarbazone ligand derived from 2-acetylethiazole viz., (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide (acetylethTSC) (compound 1), a copper(II) complex with acetylethTSC as a ligand (compound 2), a thiosemicarbazone ligand-derived from citral (compound 3) and a cobalt(III) complex with a citral-thiosemicarbazone ligand (compound 4) increased DENV2 and ZIKV replication in both mosquito C6/36 cells and human keratinocytes (HaCaT cells). Treatment of both cell lines with compounds 2 or 4 showed increased dengue viral titers at all three tested doses. Enhanced dengue viral plaque formation was also noted at the tested dose of 100μM, suggesting higher production of infectious viral particles. Treatment with the compounds 2 or 4 enhanced ZIKV and DENV2 RNA levels in HeLa cell line and primary cultures of mouse bone marrow derived dendritic cells. Also, pre- or post treatments with conjugated compounds 2 or 4 showed higher loads of ZIKV or DENV2 envelope (E) protein in HaCaT cells. No changes in loads of E-protein were found in ZIKV-infected C6/36 cells, when compounds were treated after infection. In addition, we tested bis(1,10-phenanthroline)copper(II) chloride ([Cu(phen) 2 ]Cl 2 , (compound 5) and tris(1,10-phenanthroline)cobalt(III) chloride ([Co(phen) 3 ]Cl 3 , (compound 6) that also showed enhanced DENV2 loads. Also, we found that copper(II) chloride dehydrate (CuCl 2 ·2H 2 O) or cobalt(II) chloride hexahydrate (CoCl 2 ·6H 2 O) alone had no effects as "free" cations

  19. Dysregulated miR-127-5p contributes to type II collagen degradation by targeting matrix metalloproteinase-13 in human intervertebral disc degeneration.

    Science.gov (United States)

    Hua, Wen-Bin; Wu, Xing-Huo; Zhang, Yu-Kun; Song, Yu; Tu, Ji; Kang, Liang; Zhao, Kang-Cheng; Li, Shuai; Wang, Kun; Liu, Wei; Shao, Zeng-Wu; Yang, Shu-Hua; Yang, Cao

    2017-08-01

    Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of extracellular matrix (ECM). Matrix metalloproteinase (MMP)-13 is a major enzyme that mediates the degradation of ECM components. MMP-13 has been predicted to be a potential target of miR-127-5p. However, the exact function of miR-127-5p in IDD is still unclear. We designed this study to evaluate the correlation between miR-127-5p level and the degeneration of human intervertebral discs and explore the potential mechanisms. miR-127-5p levels and MMP-13 mRNA levels were detected by quantitative real-time polymerase chain reaction (qPCR). To determine whether MMP-13 is a target of miR-127-5p, dual luciferase reporter assays were performed. miR-127-5p mimic and miR-127-5p inhibitor were used to overexpress or downregulate miR-127-5p expression in human NP cells, respectively. Small interfering RNA (siRNA) was used to knock down MMP-13 expression in human NP cells. Type II collagen expression in human NP cells was detected by qPCR, western blotting, and immunofluorescence staining. We confirmed that miR-127-5p was significantly downregulated in nucleus pulposus (NP) tissue of degenerative discs and its expression was inversely correlated with MMP-13 mRNA levels. We reveal that MMP-13 may act as a target of miR-127-5p. Expression of miR-127-5p was inversely correlated with type II collagen expression in human NP cells. Moreover, suppression of MMP-13 expression by siRNA blocked downstream signaling and increased type II collagen expression. Dysregulated miR-127-5p contributed to the degradation of type II collagen by targeting MMP-13 in human IDD. Our findings highlight that miR-127-5p may serve as a new therapeutic target in IDD. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  20. ‘Fortress Europe’: Compliance of the Dublin II Regulation with the European Convention for the Protection of Human Rights and Fundamental Freedoms

    Directory of Open Access Journals (Sweden)

    Joanna Lenart

    2012-06-01

    Full Text Available Recently, the Dublin II Regulation, a cornerstone of the emerging Common European Asylum System, has been gravely criticised, especially in context of the living conditions and general situation of asylum seekers in Greece. The main concerns regard the potential noncompliance of the Dublin II Regulation with the European Convention on Human Rights ('ECHR', particularly with Article 3 - the prohibition of torture or inhuman or degrading treatment. This article examines the competing views in this respect. It analyses the relationship between EU law and the ECHR, protection of rights of refugees under the 1951 Convention relating to the Status of Refugees and main deficiencies of the Dublin II Regulation. The analysis starts with the non-equivalent protection of asylum seekers throughout the EU and finishes with the very limited definition of a family member and case law relevant to the principle of non-refoulement. This article concludes that the Dublin II Regulation per se cannot be deemed noncompliant with the ECHR. However, it emphasises the urgent need to change relevant legal provisions, or at least enforcement, and proposes possible solutions therein.

  1. Expression of a partially deleted gene of human type II procollagen (COL2A1) in transgenic mice produces a chondrodysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Vandenberg, P.; Khillan, J.S.; Prockop, D.J.; Helminen, H.; Kontusaari, S.; Ala-Kokko, L. (Thomas Jefferson Univ., Philadelphia, PA (United States))

    1991-09-01

    A minigene version of the human gene for type II procollagen (COL2AI) was prepared that lacked a large central region containing 12 of the 52 exons and therefore 291 of the 1523 codons of the gene. The construct was modeled after sporadic in-frame deletions of collagen genes that cause synthesis of shortened pro{alpha} chains that associate with normal pro{alpha} chains and thereby cause degradation of the shortened and normal pro{alpha} chains through a process called procollagen suicide. The gene construct was used to prepare five lines of transgenic mice expressing the minigene. A large proportion of the mice expressing the minigene developed a phenotype of a chondrodysplasia with dwarfism, short and thick limbs, a short snout, a cranial bulge, a cleft palate, and delayed mineralization of bone. A number of mice died shortly after birth. Microscopic examination of cartilage revealed decreased density and organization of collagen fibrils. In cultured chondrocytes from the transgenic mice, the minigene was expressed as shortened pro{alpha}1(II) chains that were disulfide-linked to normal mouse pro{alpha}1(II) chains. Therefore, the phenotype is probably explained by depletion of the endogenous mouse type II procollagen through the phenomenon of procollagen suicide.

  2. Filling the gap. Human cranial remains from Gombore II (Melka Kunture, Ethiopia; ca. 850 ka) and the origin of Homo heidelbergensis.

    Science.gov (United States)

    Profico, Antonio; Di Vincenzo, Fabio; Gagliardi, Lorenza; Piperno, Marcello; Manzi, Giorgio

    2016-06-20

    African archaic humans dated to around 1,0 Ma share morphological affinities with Homo ergaster and appear distinct in cranio-dental morphology from those of the Middle Pleistocene that are referred to Homo heidelbergensis. This observation suggests a taxonomic and phylogenetic discontinuity in Africa that ranges across the Matuyama/Brunhes reversal (780 ka). Yet, the fossil record between roughly 900 and 600 ka is notoriously poor. In this context, the Early Stone Age site of Gombore II, in the Melka Kunture formation (Upper Awash, Ethiopia), provides a privileged case-study. In the Acheulean layer of Gombore II, somewhat more recent than 875 ±10 ka, two large cranial fragments were discovered in 1973 and 1975 respectively: a partial left parietal (Melka Kunture 1) and a right portion of the frontal bone (Melka Kunture 2), which probably belonged to the same cranium. We present here the first detailed description and computer-assisted reconstruction of the morphology of the cranial vault pertaining to these fossil fragments. Our analysis suggest that the human fossil specimen from Gombore II fills a phenetic gap between Homo ergaster and Homo heidelbergensis. This appears in agreement with the chronology of such a partial cranial vault, which therefore represents at present one of the best available candidates (if any) for the origin of Homo heidelbergensis in Africa.

  3. Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y.

    Science.gov (United States)

    Tosi, Giovanna; Pilotti, Elisabetta; Mortara, Lorenzo; De Lerma Barbaro, Andrea; Casoli, Claudio; Accolla, Roberto S

    2006-08-22

    The master regulator of MHC-II gene transcription, class II transactivator (CIITA), acts as a potent inhibitor of human T cell leukemia virus type 2 (HTLV-2) replication by blocking the activity of the viral Tax-2 transactivator. Here, we show that this inhibitory effect takes place at the nuclear level and maps to the N-terminal 1-321 region of CIITA, where we identified a minimal domain, from positions 64-144, that is strictly required to suppress Tax-2 function. Furthermore, we show that Tax-2 specifically cooperates with cAMP response element binding protein-binding protein (CBP) and p300, but not with p300/CBP-associated factor, to enhance transcription from the viral promoter. This finding represents a unique difference with respect to Tax-1, which uses all three coactivators to transactivate the human T cell leukemia virus type 1 LTR. Direct sequestering of CBP or p300 is not the primary mechanism by which CIITA causes suppression of Tax-2. Interestingly, we found that the transcription factor nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR transactivation. Thus, CIITA may inhibit Tax-2 function, at least in part, through nuclear factor Y. These findings demonstrate the dual defensive role of CIITA against pathogens: it increases the antigen-presenting function for viral determinants and suppresses HTLV-2 replication in infected cells.

  4. Crystallization and preliminary X-ray analysis of the complexes between a Fab and two forms of human insulin-like growth factor II

    International Nuclear Information System (INIS)

    Newman, Janet; Cohen, Edward H.; Cosgrove, Leah; Kopacz, Kris; Dransfield, Daniel T.; Adams, Timothy E.; Peat, Thomas S.

    2009-01-01

    Complexes of both hIGF-II and hIGF-IIE with a Fab have been crystallized and investigated by X-ray analysis. Elevated expression of insulin-like growth factor II (IGF-II) is frequently observed in a variety of human malignancies, including breast, colon and liver cancer. As IGF-II can deliver a mitogenic signal through both the type 1 insulin-like growth factor receptor (IGF-IR) and an alternately spliced form of the insulin receptor (IR-A), neutralizing the biological activity of this growth factor directly is an attractive therapeutic option. One method of doing this would be to find antibodies that bind tightly and specifically to the peptide, which could be used as protein therapeutics to lower the peptide levels in vivo and/or to block the peptide from binding to the IGF-IR or IR-A. To address this, Fabs were selected from a phage-display library using a biotinylated precursor form of the growth factor known as IGF-IIE as a target. Fabs were isolated that were specific for the E-domain C-terminal extension and for mature IGF-II. Four Fabs selected from the library were produced, complexed with IGF-II and set up in crystallization trials. One of the Fab–IGF-II complexes (M64-F02–IGF-II) crystallized readily, yielding crystals that diffracted to 2.2 Å resolution and belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 50.7, b = 106.9, c = 110.7 Å. There was one molecule of the complete complex in the asymmetric unit. The same Fab was also crystallized with a longer form of the growth factor, IGF-IIE. This complex crystallized in space group P2 1 2 1 2 1 , with unit-cell parameters a = 50.7, b = 107, c = 111.5 Å, and also diffracted X-rays to 2.2 Å resolution

  5. Doação e adoção como políticas para salvar os embriões humanos excedentes e congelados Donation and adoption as ways of saving excess frozen human embryos

    Directory of Open Access Journals (Sweden)

    Gerson Odilon Pereira

    2010-12-01

    Full Text Available Este artigo trata da divergência científica existente com relação à sobra de embriões congelados, particularmente entre a biologia, a religião, o direito e a bioética, e focando especialmente nos meios e nas formas com que cada uma dessas ciências caracteriza o início da vida. É objetivo dos autores, ainda, fornecer alternativas para a proteção do embrião humano, como a adoção por casais ou apenas por mulheres que, por razões médicas, não podem ser fertilizadas, mas que podem gestar. Em se tratando de Brasil, os autores concluem ser legal e legítimo a doação e a adoção de embrião humano para fertilização, desde que sejam considerados o princípio da dignidade da pessoa humana e mantido o sigilo sobre a identidade dos doadores de gametas, cujos dados devem permanecer registrados de forma permanente no centro onde ocorreu a fertilização.This article deals with the existing scientific divergence with regard to the surplus of frozen embryos, especially between biology, religion, the law and bioethics, with a specific focus on the ways in which each of these areas determines the onset of life. The aim of the authors is to suggest alternatives that protect the human embryo, such as adoption by couples or by single women, who, for medical reasons, are infertile, but are capable of bearing a child. In the case of Brazil, the authors conclude that it is legal and legitimate to donate and adopt human embryos for fertilization, so long as the principle of human dignity is upheld and confidentiality maintained regarding the identity of the donors of the gametes, whose data should remain on file permanently at the center where fertilization occurred.

  6. Elecciones 2003: spots políticos y cultura política

    OpenAIRE

    Concepción Virriel

    2004-01-01

    El presente trabajo aborda el tema de las elecciones federales de 2003, en especial el fenómeno del abstencionismo. Para ello se vincula el comportamiento electoral en dichas elecciones con la cultura política, en donde los aspectos básicos son la cultura del fraude heredada de los gobiernos priístas y la redefinición de los partidos políticos ante una nueva coyuntura, y cómo éstos aspectos influyeron en la forma de comunicarse mediante sus spots. El análisis de dichos spots comprende el anál...

  7. Ni(ii) ions cleave and inactivate human alpha-1 antitrypsin hydrolytically, implicating nickel exposure as a contributing factor in pathologies related to antitrypsin deficiency.

    Science.gov (United States)

    Wezynfeld, Nina Ewa; Bonna, Arkadiusz; Bal, Wojciech; Frączyk, Tomasz

    2015-04-01

    Human alpha-1 antitrypsin (AAT) is an abundant serum protein present at a concentration of 1.0-1.5 g L(-1). AAT deficiency is a genetic disease that manifests with emphysema and liver cirrhosis due to the accumulation of a misfolded AAT mutant in hepatocytes. Lung AAT amount is inversely correlated with chronic obstructive pulmonary disease (COPD), a serious and often deadly condition, with increasing frequency in the aging population. Exposure to cigarette smoke and products of fossil fuel combustion aggravates AAT deficiency and COPD according to mechanisms that are not fully understood. Taking into account that these fumes contain particles that can release nickel to human airways and skin, we decided to investigate interactions of AAT with Ni(ii) ions within the paradigm of Ni(ii)-dependent peptide bond hydrolysis. We studied AAT protein derived from human blood using HPLC, SDS-PAGE, and mass spectrometry. These studies were aided by spectroscopic experiments on model peptides. As a result, we identified three hydrolysis sites in AAT. Two of them are present in the N-terminal part of the molecule next to each other (before Thr-13 and Ser-14 residues) and effectively form one N-terminal cleavage site. The single C-terminal cleavage site is located before Ser-285. The N-terminal hydrolysis was more efficient than the C-terminal one, but both abolished the ability of AAT to inhibit trypsin in an additive manner. Nickel ions bound to hydrolysis products demonstrated an ability to generate ROS. These results implicate Ni(ii) exposure as a contributing factor in AAT-related pathologies.

  8. Expression and role of the angiotensin II AT2 receptor in human prostate tissue: in search of a new therapeutic option for prostate cancer.

    Science.gov (United States)

    Guimond, Marie-Odile; Battista, Marie-Claude; Nikjouitavabi, Fatemeh; Carmel, Maude; Barres, Véronique; Doueik, Alexandre A; Fazli, Ladan; Gleave, Martin; Sabbagh, Robert; Gallo-Payet, Nicole

    2013-07-01

    Evidence shows that angiotensin II type 1 receptor (AT1R) blockers may be associated with improved outcome in prostate cancer patients. It has been proposed that part of this effect could be due to angiotensin II type 2 receptor (AT2R) activation, the only active angiotensin II receptor in this situation. This study aimed to characterize the localization and expression of AT2R in prostate tissues and to assess its role on cell morphology and number in prostatic epithelial cells in primary culture. AT2R and its AT2R-interacting protein (ATIP) expression were assessed on non-tumoral and tumoral human prostate using tissue microarray immunohistochemistry, binding assay, and Western blotting. AT2R effect on cell number was measured in primary cultures of epithelial cells from non-tumoral human prostate. AT2R was localized at the level of the acinar epithelial layer and its expression decreased in cancers with a Gleason score 6 or higher. In contrast, ATIP expression increased with cancer progression. Treatment of primary cell cultures from non-tumoral prostate tissues with C21/M024, a selective AT2R agonist, alone or in co-incubation with losartan, an AT1R antagonist, significantly decreased cell number compared to untreated cells. AT2R and ATIP are present in non-tumoral human prostate tissues and differentially regulated according to Gleason score. The decrease in non-tumoral prostate cell number upon selective AT2R stimulation suggests that AT2R may have a protective role against prostate cancer development. Treatment with a selective AT2R agonist could represent a new approach for prostate cancer prevention or for patients on active surveillance. Copyright © 2013 Wiley Periodicals, Inc.

  9. Quercetin alters the DNA damage response in human hematopoietic stem and progenitor cells via TopoII- and PI3K-dependent mechanisms synergizing in leukemogenic rearrangements.

    Science.gov (United States)

    Biechonski, Shahar; Gourevich, Dana; Rall, Melanie; Aqaqe, Nasma; Yassin, Muhammad; Zipin-Roitman, Adi; Trakhtenbrot, Luba; Olender, Leonid; Raz, Yael; Jaffa, Ariel J; Grisaru, Dan; Wiesmuller, Lisa; Elad, David; Milyavsky, Michael

    2017-02-15

    Quercetin (Que) is an abundant flavonoid in the human diet and high-concentration food supplement with reported pro- and anti-carcinogenic activities. Topoisomerase II (TopoII) inhibition and subsequent DNA damage induction by Que was implicated in the mixed lineage leukemia gene (MLL) rearrangements that can induce infant and adult leukemias. This notion raised concerns regarding possible genotoxicities of Que in hematopoietic stem and progenitor cells (HSPCs). However, molecular targets mediating Que effects on DNA repair relevant to MLL translocations have not been defined. In this study we describe novel and potentially genotoxic Que activities in suppressing non-homologous end joining and homologous recombination pathways downstream of MLL cleavage. Using pharmacological dissection of DNA-PK, ATM and PI3K signalling we defined PI3K inhibition by Que with a concomitant decrease in the abundance of key DNA repair genes to be responsible for DNA repair inhibition. Evidence for the downstream TopoII-independent mutagenic potential of Que was obtained by documenting further increased frequencies of MLL rearrangements in human HSPCs concomitantly treated with Etoposide and Que versus single treatments. Importantly, by engaging a tissue engineered placental barrier, we have established the extent of Que transplacental transfer and hence provided the evidence for Que reaching fetal HSPCs. Thus, Que exhibits genotoxic effects in human HSPCs via different mechanisms when applied continuously and at high concentrations. In light of the demonstrated Que transfer to the fetal compartment our findings are key to understanding the mechanisms underlying infant leukemia and provide molecular markers for the development of safety values. © 2016 UICC.

  10. Prototype Theory Based Feature Representation for PolSAR Images

    OpenAIRE

    Huang Xiaojing; Yang Xiangli; Huang Pingping; Yang Wen

    2016-01-01

    This study presents a new feature representation approach for Polarimetric Synthetic Aperture Radar (PolSAR) image based on prototype theory. First, multiple prototype sets are generated using prototype theory. Then, regularized logistic regression is used to predict similarities between a test sample and each prototype set. Finally, the PolSAR image feature representation is obtained by ensemble projection. Experimental results of an unsupervised classification of PolSAR images show that our...

  11. Human and Organizational Issues in the Army After Next - II: A Conference Held 24-26 June 1998

    National Research Council Canada - National Science Library

    Drillings, Michael

    1998-01-01

    .... Some of the topics discussed were Future Personnel Management, Teams and Organizations, Information Technology, The Leadership Challenge, Army Science Board of Human Behavior in Combat and Strategic...

  12. 3ircular dichroism simulation shows a site-II-to-site-I displacement of human serum albumin-bound diclofenac by ibuprofen

    OpenAIRE

    Yamasaki, Keishi; Rahman, Mohammed Hablbur; Tsutsumi, Yasuhiro; Maruyama, Toru; Ahmed, Shamim; Kragh-Hansen; Otagiri, Masaki

    2000-01-01

    Purpose: The purpose of this study was to confirm the hypothesis that a site-II-to-site-I displacement takes place when some nonsteroidal anti-inflammatory drugs are displaced by another drug from their high-affinity binding site to a site of lower affinity on human serum albumin (HSA).Methods: Diclofenac, sodium salt, was used as a representative example because of its prominent reversal of the Cotton effect. Effects of site-specific drugs on the free fraction of diclofenac were determined b...

  13. Human Retroviruses and AIDS. A compilation and analysis of nucleic acid and amino acid sequences: I--II; III--V

    Energy Technology Data Exchange (ETDEWEB)

    Myers, G.; Korber, B. [eds.] [Los Alamos National Lab., NM (United States); Wain-Hobson, S. [ed.] [Laboratory of Molecular Retrovirology, Pasteur Inst.; Smith, R.F. [ed.] [Baylor Coll. of Medicine, Houston, TX (United States). Dept. of Pharmacology; Pavlakis, G.N. [ed.] [National Cancer Inst., Frederick, MD (United States). Cancer Research Facility

    1993-12-31

    This compendium and the accompanying floppy diskettes are the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses. The scope of the compendium and database is best summarized by the five parts that it comprises: (I) HIV and SIV Nucleotide Sequences; (II) Amino Acid Sequences; (III) Analyses; (IV) Related Sequences; and (V) Database Communications. Information within all the parts is updated at least twice in each year, which accounts for the modes of binding and pagination in the compendium.

  14. Desarrollo vocacional y política pública

    OpenAIRE

    Watts, Anthony G.

    2000-01-01

    El trabajo analiza la base para el interés político en los servicios de desarrollo vocacional, y la manera en la cual esta base está siendo fortalecida por las actuales transformaciones en el trabajo y en el desarrollo vocacional. Se exploran los papeles potenciales de la política pública en los servicios de desarrollo vocacional así como las formas en las que dichos servicios pueden influenciar el proceso de la creación de políticas. Se identifican una gama de temas de política relacionados ...

  15. Política, violencia y literatura

    Directory of Open Access Journals (Sweden)

    Kohut, Karl

    2002-06-01

    Full Text Available Tomando como punto de partida la opinión general de que América Latina es el continente violento por excelencia y la hipótesis defendida por Ariel Dorfman (1972 se analiza aquí la cuestión de la violencia política, ciñéndose a la literatura de la segunda mitad del siglo XX. Tras discutir las definiciones (divergentes de la violencia propuestas por la filosofía política, se pasa a una fenomenología de la violencia en la literatura, examinando hasta qué punto y en qué sentido ésta sería el carácter distintivo de la literatura latinoamericana. Finalmente, se analiza la metarreflexión sobre la violencia política en la literatura ficcional, centrándose en tres puntos: (1 el (presunto ser violento del mundo latinoamericano, (2 la violencia estatal, y (3 la violencia de la resistencia. Se constata, entre otras cosas, que ha habido una tendencia a atacar la violencia estatal y defender la de la resistencia; tendencia comprensible en tiempos de dictadura, pero que se vuelve problemática bajo una democracia. Dos preguntas cierran este trabajo: hasta qué punto la violencia es un fenómeno de la cultura, que crece en su mismo seno, y no un fenómeno extracultural dirigido contra ella, y hasta dónde la libertad individual y la seguridad cívica pueden ser conciliadas, punto que ha ocupado un lugar central en la discusión internacional después de los acontecimientos del 11 de septiembre.

  16. Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines.

    KAUST Repository

    Foley, Joseph W

    2013-10-20

    BACKGROUND: High-occupancy target (HOT) regions are compact genome loci occupied by many different transcription factors (TFs). HOT regions were initially defined in invertebrate model organisms, and we here show that they are a ubiquitous feature of the human gene-regulation landscape. RESULTS: We identified HOT regions by a comprehensive analysis of ChIP-seq data from 96 DNA-associated proteins in 5 human cell lines. Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance. TF occupancy varies quantitatively within human HOT regions; we used this variation to discover novel associations between TFs. The sequence motif associated with any given TF\\'s direct DNA binding is somewhat predictive of its empirical occupancy, but a great deal of occupancy occurs at sites without the TF\\'s motif, implying indirect recruitment by another TF whose motif is present. CONCLUSIONS: Mammalian HOT regions are regulatory hubs that integrate the signals from diverse regulatory pathways to quantitatively tune the promoter for RNA polymerase II recruitment.

  17. Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines.

    KAUST Repository

    Foley, Joseph W; Sidow, Arend

    2013-01-01

    BACKGROUND: High-occupancy target (HOT) regions are compact genome loci occupied by many different transcription factors (TFs). HOT regions were initially defined in invertebrate model organisms, and we here show that they are a ubiquitous feature of the human gene-regulation landscape. RESULTS: We identified HOT regions by a comprehensive analysis of ChIP-seq data from 96 DNA-associated proteins in 5 human cell lines. Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance. TF occupancy varies quantitatively within human HOT regions; we used this variation to discover novel associations between TFs. The sequence motif associated with any given TF's direct DNA binding is somewhat predictive of its empirical occupancy, but a great deal of occupancy occurs at sites without the TF's motif, implying indirect recruitment by another TF whose motif is present. CONCLUSIONS: Mammalian HOT regions are regulatory hubs that integrate the signals from diverse regulatory pathways to quantitatively tune the promoter for RNA polymerase II recruitment.

  18. La polémica del nacionalismo

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    Germán Posada

    1961-10-01

    Full Text Available La polémica empezó con el artículo de Hernando Téllez, hace veinte días. Con el pretexto de defender a los escritores de su propia generación, a quienes, según él, se viene acusando sistemáticamente de producir una literatura desarraigada y ausente de la vida nacional, Téllez se lanzó a combatir las teorías de " nacionalismo literario'' que actualmente se agitan en Colombia.

  19. Dos Partidos Políticos

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    Marquessuel Dantas de Souza

    2017-09-01

    Full Text Available A presente resenha se refere ao interessante texto de Simone Weil (Note sur la suppression générale des partis politiques - de 1940, escrito em Londres, traduzido e publicado pela iniciativa audaciosa da Editora Ayiné. Originalmente publicado na coletânea intitulada ÉCRITS DE LONDRES et dernières lettres - Éditions Gallimard (1957, este texto apresenta de forma singular o que significa um partido político; algo de muita importância para e na vida social do homem moderno.

  20. Amor y política.

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    Hernando Bernal.

    1998-09-01

    Full Text Available Este trabajo pretende hacer una serie de consideraciones que apuntan sobre todo a extraer una definición de lo que es «la política» para el psicoanálisis a partir de una observación que hace Jacques Alain Miller en su texto Lógicas de la vida amorosa sobre cómo Freud introduce una «teoría política» a partir de su texto Psicología de las masas y análisis del yo.En dicho texto Freud hace ver el poder ordenador y apaciguador del amor significante amo en la medida en que una masa no es más que el amor uniendo a muchas personas y reiterado en cada una de ellas. Las fuerzas armadas y la Iglesia son un buen ejemplo de ello.Pero a pesar de la cohesión amorosa de la humanidad por el poder unificante del amor, resta siempre un malestar. El malestar que persiste en la cultura testimonia del fracaso del amor para resolver el empuje del hombre a satisfacerse con el mal. El significante amo no parece entonces solucionar la paradoja del goce. De aquí que preguntarse sobre adónde vaya el goce en el orden social sea también, para el psicoanálisis, una cuestión política. Jacques- Alain Miller observa, en su texto Lógicas de la vida amorosa, cómo, a partir de la Psicología de las masas y análisis del yo, se puede extraer de Freud una «teoría política», que se vincula muy estrechamente con el amor. Esto porque La Psicología de las masas... enseña sobre el poder ordenador y apaciguador del amor, o mejor, del significante «amor» como significante Amo, lo que se puede escribir de la siguiente manera con ayuda de la «teoría de los discursos» o «teoría del vínculo social» de Lacan.

  1. Application of the human needs conceptual model of dental hygiene to the role of the clinician : part II.

    Science.gov (United States)

    Walsh, M M; Darby, M

    1993-01-01

    In summary, the theories of Maslow and of Yura and Walsh have been highlighted as background for understanding the human needs conceptual model of dental hygiene. In addition, 11 human needs have been identified and defined as being especially related to dental hygiene care, and a sample evaluation tool for their clinical assessment and a dental hygiene care plan have been presented. The four concepts of client, environment, health/oral health, and dental hygiene actions explained in terms of human need theory, and the 11 human needs related to dental hygiene care constitute the human needs conceptual model of dental hygiene. Within the framework of the human needs conceptual model of dental hygiene, the dental hygiene process is a systematic approach to dental hygiene care that involves assessment of the 11 human needs related to dental hygiene care; analysis of deficits in these needs; determination of the dental hygiene care plan based on identified deficits; implementation of dental hygiene interventions stated in the care plan; and evaluation of the effectiveness of dental hygiene interventions in achieving specific goals, including subsequent reassessment and revision of the dental hygiene care plan. This human needs conceptual model for dental hygiene provides a guide for comprehensive and humanistic client care. This model allows the dental hygienist to view each client (whether an individual or a group) holistically to prevent oral disease and to promote health and wellness. Dental hygiene theorists are encouraged to expand this model or to develop additional conceptual models based on dental hygiene's paradigm.

  2. New modulated design, docking and synthesis of carbohydrate-conjugate heterobimetallic CuII-SnIV complex as potential topoisomerase II inhibitor: in vitro DNA binding, cleavage and cytotoxicity against human cancer cell lines.

    Science.gov (United States)

    Tabassum, Sartaj; Afzal, Mohd; Arjmand, Farukh

    2014-03-03

    New carbohydrate-conjugate heterobimetallic complexes [C₂₂H₅₀N₆O₁₃CuSnCl₂] (3) and [C₂₂H₅₈N₆O₁₇NiSnCl₂] (4) were synthesized from their monometallic analogs [C₂₂H₅₂N₆O₁₃Cu] (1) and [C₂₂H₆₀N₆O₁₇Ni] (2) containing N-glycoside ligand (L). In vitro DNA binding studies of L and complexes (1-4) with CT DNA were carried out by employing various biophysical and molecular docking techniques which revealed that heterobimetallic complex 3 strongly binds to DNA in comparison to 4, monometallic complexes (1 and 2) and the free ligand. Complex 3 cleaves pBR322 DNA via hydrolytic pathway (confirmed by T4 DNA ligase assay) and inhibited Topo-II activity in a dose-dependent manner. Furthermore, complex 3 was docked into the ATPase domain of human-Topo-II in order to probe the possible mechanism of inhibition. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  3. A segurança alimentar e nutricional e o uso da abordagem de direitos humanos no desenho das políticas públicas para combater a fome e a pobreza Food and nutritional security and the use of a human rights-based approach on the development of public policies to fight hunger and poverty

    Directory of Open Access Journals (Sweden)

    Maria de Fátima Machado de Albuquerque

    2009-12-01

    Full Text Available Este ensaio tem como objetivo enfatizar a importância da utilização da abordagem de direitos humanos no desenho das políticas públicas para combater a fome e a pobreza no Brasil. Inicialmente foi apresentado um marco teórico sobre o conceito de segurança alimentar e nutricional e o direito humano à alimentação adequada. Também foram identificadas as obrigações do Estado para a realização do direito humano à alimentação adequada, bem como o que se identifica como potenciais violações deste direito. Depois se buscou discutir o significado de uma abordagem baseada nos direitos e como esta abordagem pode contribuir para a promoção do direito à alimentação adequada. Foi realizada uma breve reflexão sobre a questão da (insegurança alimentar, suas diversas formas de avaliação e sobre a importância de investigar mais detalhadamente as repercussões desta questão sobre o indivíduo e a família, inclusive daquelas que participam de programas sociais.This essay aims to discuss the meaning of a human rights-based approach in the context of the public policies used in the fight against hunger and poverty in Brazil. Some aspects were presented such as the accepted concepts of food and nutritional security and the human right to appropriate nutrition. The obligations of the State to fulfill the human right to appropriate nutrition were also identified as well as that which is seen as potential violations of this right. Then, the meaning of a rights-based approach and how this approach can contribute to promote the right to appropriate nutrition were discussed. A concise reflection was done on the food (insecurity issue, its many ways of assessment and the importance of investigating in a more detailed manner the repercussions of this issue on individuals and families, including those who are benefited by social programs.

  4. Políticas de reconhecimento uma novidade das políticas sociais do PT?

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    Krischke, Paulo Jose Duval da Silva

    2004-01-01

    Full Text Available O presente trabalho levanta a hipótese de que as ações de governo do PT estão inovando significativamente na necessária convergência (cf. Fraser, 1999; Honnetch, 2003 entre as tradicionais políticas de redistribuição sócio-econômica, e uma nova diretriz de reconhecimento das diferenças sócio-políticas e culturais. O argumento retoma a trajetória sindical do PT e os efeitos das políticas participativas, nas mudanças da cultura política em várias partes do país. Entre esses efeitos, o crescente apoio à democracia parece relacionar-se ao reconhecimento do direito à diferença e ao pluralismo - principalmente entre a juventude e naqueles locais onde o PT tem governado na última década

  5. Chiral Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine and its Phase I and II Metabolites following Controlled Administration to Humans.

    OpenAIRE

    Steuer Andrea E; Schmidhauser Corina; Schmid Yasmin; Rickli Anna; Liechti Matthias E; Kraemer Thomas

    2015-01-01

    Generally, pharmacokinetic studies on 3,4-methylenedioxymethamphetamine (MDMA) in blood have been performed after conjugate cleavage, without taking into account that phase II metabolites represent distinct chemical entities with their own effects and stereoselective pharmacokinetics. The aim of the present study was to stereoselectively investigate the pharmacokinetics of intact glucuronide and sulfate metabolites of MDMA in blood plasma after a controlled single MDMA dose. Plasma samples fr...

  6. Insight into eukaryotic topoisomerase II-inhibiting fused heterocyclic compounds in human cancer cell lines by molecular docking.

    Science.gov (United States)

    Taskin, T; Yilmaz, S; Yildiz, I; Yalcin, I; Aki, E

    2012-01-01

    Etoposide is effective as an anti-tumour drug by inhibiting eukaryotic DNA topoisomerase II via establishing a covalent complex with DNA. Unfortunately, its wide therapeutic application is often hindered by multidrug resistance (MDR), low water solubility and toxicity. In our previous study, new derivatives of benzoxazoles, benzimidazoles and related fused heterocyclic compounds, which exhibited significant eukaryotic DNA topoisomerase II inhibitory activity, were synthesized and exhibited better inhibitory activity compared with the drug etoposide itself. To expose the binding interactions between the eukaryotic topoisomerase II and the active heterocyclic compounds, docking studies were performed, using the software Discovery Studio 2.1, based on the crystal structure of the Topo IIA-bound G-segment DNA (PDB ID: 2RGR). The research was conducted on a selected set of 31 fused heterocyclic compounds with variation in structure and activity. The structural analyses indicate coordinate and hydrogen bonding interactions, van der Waals interactions and hydrophobic interactions between ligands and the protein, as Topo IIA-bound G-segment DNA are responsible for the preference of inhibition and potency. Collectively, the results demonstrate that the compounds 1a, 1c, 3b, 3c, 3e and 4a are significant anti-tumour drug candidates that should be further studied.

  7. Human T-cell Lymphotropic Virus types I and II (HTLV-I/II in French Guiana: clinical and molecular epidemiology Os Vírus T-Linfotrópicos Humanos tipo I (HTLV-I e tipo II (HTLV-II na Guiana Francesa: epidemiologia clínica e molecular

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    Mirdad Kazanji

    2003-10-01

    Full Text Available We review here the epidemiological studies performed by our group on human retrovirus HTLV-I and HTLV-II infections and the associated diseases in French Guiana since 1984. French Guiana is an overseas French administrative district located between Brazil and Surinam. Its population is characterized by a large variety of ethnic groups, including several populations of African origin and various populations of Amerindian origin. Several epidemiological studies of large samples of pregnant women and in remote villages showed that HTLV-I is highly endemic in this area but is restricted to groups of African origin, especially the Noir-Marrons. In this endemic population, the results of segregation analysis in a genetic epidemiological study were consistent with the presence of a dominant major gene predisposing to HTLV-I infection, especially in children. In contrast, HTLV-II infection appears to be rare in French Guiana, having been found in only a few individuals of Brazilian origin. From a molecular point of view, the HTLV-I strains present in the Noir-Marrons, Creoles and Amerindians appear to originate from Africa, as they belong to the large cosmopolitan molecular subtype A.Os autores apresentam uma revisão dos estudos epidemiológicos realizados pelo seu grupo de pesquisa sobre a infecção pelos vírus T-linfotrópicos humanos tipo I (HTLV-I e tipo II (HTLV-II e doenças associadas na Guiana Francesa, desde 1984. A Guiana Francesa é um Departamento de Ultramar da França, situado entre o Brasil e o Suriname. A população é caracterizada por uma grande variedade de grupos étnicos, incluindo diversas comunidades de origem africana e outras de origem indígena. Diversos inquéritos epidemiológicos sobre gestantes e em aldeias remotas mostraram que o HTLV-I é altamente endêmico nessas áreas, mas que o vírus é restrito a grupos de origem africana, particularmente os Noir-Marrons. Nessa população endêmica, os resultados de uma an

  8. Effect of Cell Sheet Manipulation Techniques on the Expression of Collagen Type II and Stress Fiber Formation in Human Chondrocyte Sheets.

    Science.gov (United States)

    Wongin, Sopita; Waikakul, Saranatra; Chotiyarnwong, Pojchong; Siriwatwechakul, Wanwipa; Viravaidya-Pasuwat, Kwanchanok

    2018-03-01

    Cell sheet technology is applied to human articular chondrocytes to construct a tissue-like structure as an alternative treatment for cartilage defect. The effect of a gelatin manipulator, as a cell sheet transfer system, on the quality of the chondrocyte sheets was investigated. The changes of important chondrogenic markers and stress fibers, resulting from the cell sheet manipulation, were also studied. The chondrocyte cell sheets were constructed with patient-derived chondrocytes using a temperature-responsive polymer and a gelatin manipulator as a transfer carrier. The properties of the cell sheets, including sizes, expression levels of collagen type II and I, and the localization of the stress fibers, were assessed and compared with those of the cell sheets harvested without the gelatin manipulator. Using the gelatin manipulator, the original size of the chondrocyte cell sheets was retained with abundant stress fibers, but with a decrease in the expression of collagen type II. Without the gelatin manipulator, although the cell shrinkage occurred, the cell sheet with suppressed stress fiber formation showed significantly higher levels of collagen type II. These results support our observations that stress fiber formation in chondrocyte cell sheets affected the production of chondrogenic markers. These densely packed tissue-like structures possessed a good chondrogenic activity, indicating their potential for use in autologous chondrocyte implantation to treat cartilage defects.

  9. Tyrosine411 and Arginine410 of Human Serum Albumin Play an Important Role in the Binding of Sodium 4-Phenylbutyrate to Site II.

    Science.gov (United States)

    Enokida, Taisuke; Yamasaki, Keishi; Okamoto, Yuko; Taguchi, Kazuaki; Ishiguro, Takako; Maruyama, Toru; Seo, Hakaru; Otagiri, Masaki

    2016-06-01

    Sodium 4-phenylbutyrate (PB) has many pharmacological activities; therefore extending its clinical use to the treatment of a wider variety of diseases would be desirable. However, our knowledge of the binding of PB to plasma proteins is not extensive. To address this issue in more detail, we characterized the protein binding of PB. Binding experiments showed that PB mainly binds to human serum albumin (HSA) in plasma. PB was also found to bind to a single site on HSA, which was identified as site II by fluorescent probe displacement experiment. Furthermore, an appropriate alkyl chain length and a carboxylic group in the PB structure were required for PB binding to HSA, suggesting that hydrophobic (and van der Waals) and electrostatic interactions are involved as binding modes. The contributions of hydrogen bonding and/or van der Waals interactions were also indicated by thermodynamic analyses. Tyrosine411 and arginine410 were identified as being involved in the binding of PB to site II, based on binding experiments using chemically modified- and mutant-HSA preparations. In conclusion, the available evidence indicates that PB binds to site II of HSA with assistance by multiple forces and that tyrosine411 and arginine410 both play important roles in this phenomenon. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  10. Dinâmica Institucional, Políticas Públicas e o Desempenho Político Ambiental Brasileiro

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    Diego de Freitas Rodrigues

    2011-12-01

    Full Text Available Este estudo buscou analisar os efeitos da interdependência entre instituições políticas e modelos de desenvolvimento no desempenho de políticas ambientais no Brasil. A hipótese central do trabalho é que, dada a interdependência entre os organismos responsáveis pelas políticas ambientais e padrões de desenvolvimento pouco responsivos à complexidade ambiental, ocorre uma dispersão de poder decisório incentivando o modelo de desenvolvimento de alto carbono. Além de revisão da literatura em Políticas Públicas e Economia Ecológica, foram operacionalizadas (1 uma análise do desenho político-institucional brasileiro e (2 o quadro de gastos públicos do governo federal brasileiro com meio ambiente. Dois resultados foram observados: 1o o desenho e as competências das instituições políticas responsáveis pela formulação e implementação de políticas públicas interferem na maior eficiência de políticas ambientais; 2o quanto maior a abertura institucional, maior a tendência de paralisia decisória na formulação e implementação de políticas públicas ambientais.

  11. Croce, Gramsci e a "autonomia da política"

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    Álvaro Bianchi

    2007-11-01

    Full Text Available Na reflexão que Gramsci desenvolveu nos Quaderni del carcere, o tema da autonomia da política ocupa uma importante posição. Foi com base nessa reflexão que Gramsci desenvolveu sua pesquisa a respeito de política e da possibilidade de uma ciência política. Segundo Benedetto Croce, cabia a Nicolau Maquiavel o mérito de ter afirmado pela primeira vez a autonomia da política. Para Croce, essa autonomia permitia estabelecer uma distinção radical entre ética e política e entre "filosofia da política" e "ciência empírica da política". Gramsci tomou criticamente a reflexão croceana como ponto de partida de sua leitura de Maquiavel. O reconhecimento da autonomia da política implicava que esta não poderia ser reduzida à religião ou à ética. Como campo do conhecimento e como atividade, a ciência política e a política tinham regras próprias, que as distinguiam de outras formas do conhecimento e da atividade humana. Mas tal "autonomia" não implicava, para o marxista sardo, uma separação radical entre política e moral. Por essa razão, Gramsci encontrava em Maquiavel um precursor da filosofia da práxis em sentido pleno, ou seja, o criador de uma "ciência-ação revolucionária".

  12. Dual Inhibition of Topoisomerase II and Tyrosine Kinases by the Novel Bis-Fluoroquinolone Chalcone-Like Derivative HMNE3 in Human Pancreatic Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Yong-Chao Ma

    Full Text Available Both tyrosine kinase and topoisomerase II (TopII are important anticancer targets, and their respective inhibitors are widely used in cancer therapy. However, some combinations of anticancer drugs could exhibit mutually antagonistic actions and drug resistance, which further limit their therapeutic efficacy. Here, we report that HMNE3, a novel bis-fluoroquinolone chalcone-like derivative that targets both tyrosine kinase and TopII, induces tumor cell proliferation and growth inhibition. The viabilities of 6 different cancer cell lines treated with a range of HMNE3 doses were detected using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Cellular apoptosis was determined using Hoechst 33258 fluorescence staining and the terminal deoxynucleotidyl transferase (TdT dUTP nick-end labeling (TUNEL assay. The expression of activated Caspase-3 was examined by immunocytochemistry. The tyrosine kinase activity was measured with a human receptor tyrosine kinase (RTK detection kit using a horseradish peroxidase (HRP-conjugated phosphotyrosine (pY20 antibody as the substrate. The topoisomerase II activity was measured using agarose gel electrophoresis with the DNA plasmid pBR322 as the substrate. The expression levels of the P53, Bax, Bcl-2, Caspase-3, -8, -9, p-cSrc, c-Src and topoisomerase II proteins were detected by western blot analysis. The proliferation of five of the six cancer cell lines was significantly inhibited by HMNE3 at 0.312 to 10 μmol/L in a time- and dose-dependent manner. Treatment of the Capan-1 and Panc-1 cells with 1.6 to 3.2 μM HMNE3 for 48 h significantly increased the percentage of apoptotic cells (P<0.05, and this effect was accompanied by a decrease in tyrosine kinase activity. HMNE3 potentially inhibited tyrosine kinase activity in vitro with an IC50 value of 0.64±0.34 μmol/L in Capan-1 cells and 3.1±0.86 μmol/L in Panc-1 cells. The activity of c-Src was significantly inhibited by HMNE3 in a dose

  13. Increased cartilage type II collagen degradation in patients with osteogenesis imperfecta used as a human model of bone type I collagen alterations.

    Science.gov (United States)

    Rousseau, Jean-Charles; Chevrel, Guillaume; Schott, Anne-Marie; Garnero, Patrick

    2010-04-01

    We investigated whether cartilage degradation is altered in adult patients with mild osteogenesis imperfecta (OI) used as a human model of bone type I collagen-related osteoarthritis (OA). Sixty-four adult patients with OI (39% women, mean age+/-SD: 37+/-12 years) and 64 healthy age-matched controls (54% women, 39+/-7 years) were included. We also compared data in 87 patients with knee OA (73% women, 63+/-8 years, mean disease duration: 6 years) and 291 age-matched controls (80% women, 62+/-10 years). Urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), a marker of cartilage degradation, urinary helical peptide of type I collagen (Helix-I), a marker of bone resorption, and the urinary ratio between non-isomerised/isomerised (alpha/beta CTX-I) type I collagen C-telopeptide, a marker of type I collagen maturation, were measured. Patients with OI had CTX-II levels similar to those of subjects with knee OA (p=0.89; mean+/-SEM; 460+/-57 ng/mmol Cr for OI group and 547+/-32 ng/mmol Cr for OA group) and significantly higher than both young (144+/-7.8 ng/mmol Cr, p<0.0001) and old controls (247+/-7 ng/mmol Cr, p<0.0001). In patients with OI, increased Helix-I (p<0.0001) and alpha/beta CTX-I (p=0.0067) were independently associated with increased CTX-II and together explained 26% of its variance (p< 0.0001). In patients with knee OA, increased levels of alpha/beta CTX-I ratio were also associated with higher CTX-II levels. Adult patients with OI or knee OA are characterized by increased cartilage type II collagen degradation, which is associated with increased type I collagen degradation for OI and lower type I collagen maturation for both OI and OA. These data suggest that both quantitative and qualitative alterations of bone type I collagen metabolism are involved in increased cartilage degradation in patients with OI or knee OA. Copyright 2009 Elsevier Inc. All rights reserved.

  14. Human YKL39 (chitinase 3-like protein 2), an osteoarthritis-associated gene, enhances proliferation and type II collagen expression in ATDC5 cells

    International Nuclear Information System (INIS)

    Miyatake, Kazumasa; Tsuji, Kunikazu; Yamaga, Mika; Yamada, Jun; Matsukura, Yu; Abula, Kahaer; Sekiya, Ichiro; Muneta, Takeshi

    2013-01-01

    Highlights: ► hYKL-39 expression is increased in osteoarthritic articular chondrocytes. ► To examine the molecular functions of hYKL-39 in chondrocytes, we overexpressed hYKL-39 in chondrocytic ATDC5 cells. ► hYKL-39 enhanced proliferation and colony formation in ATDC5 cells. ► hYKL-39 increased type II collagen expression in ATDC5 cells treated with chondrogenic medium. -- Abstract: Human YKL39 (chitinase 3-like protein 2/CHI3L2) is a secreted 39 kDa protein produced by articular chondrocytes and synoviocytes. Recent studies showed that hYKL-39 expression is increased in osteoarthritic articular chondrocytes suggesting the involvement of hYKL-39 in the progression of osteoarthritis (OA). However little is known regarding the molecular function of hYKL-39 in joint homeostasis. Sequence analyses indicated that hYKL-39 has significant identity with the human chitotorisidase family molecules, although it is considered that hYKL-39 has no enzymatic activity since it lacks putative chitinase catalytic motif. In this study, to examine the molecular function of hYKL-39 in chondrocytes, we overexpressed hYKL-39 in ATDC5 cells. Here we report that hYKL-39 enhances colony forming activity, cell proliferation, and type II collagen expression in these cells. These data suggest that hYKL-39 is a novel growth and differentiation factor involved in cartilage homeostasis

  15. Human YKL39 (chitinase 3-like protein 2), an osteoarthritis-associated gene, enhances proliferation and type II collagen expression in ATDC5 cells

    Energy Technology Data Exchange (ETDEWEB)

    Miyatake, Kazumasa [Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo (Japan); Tsuji, Kunikazu, E-mail: ktsuji.gcoe@tmd.ac.jp [International Research Center for Molecular Science in Tooth and Bone Diseases (Global Center of Excellence Program), Tokyo Medical and Dental University, Tokyo (Japan); Yamaga, Mika; Yamada, Jun; Matsukura, Yu; Abula, Kahaer [Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo (Japan); Sekiya, Ichiro [Section of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo (Japan); Muneta, Takeshi [Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo (Japan); International Research Center for Molecular Science in Tooth and Bone Diseases (Global Center of Excellence Program), Tokyo Medical and Dental University, Tokyo (Japan)

    2013-02-01

    Highlights: ► hYKL-39 expression is increased in osteoarthritic articular chondrocytes. ► To examine the molecular functions of hYKL-39 in chondrocytes, we overexpressed hYKL-39 in chondrocytic ATDC5 cells. ► hYKL-39 enhanced proliferation and colony formation in ATDC5 cells. ► hYKL-39 increased type II collagen expression in ATDC5 cells treated with chondrogenic medium. -- Abstract: Human YKL39 (chitinase 3-like protein 2/CHI3L2) is a secreted 39 kDa protein produced by articular chondrocytes and synoviocytes. Recent studies showed that hYKL-39 expression is increased in osteoarthritic articular chondrocytes suggesting the involvement of hYKL-39 in the progression of osteoarthritis (OA). However little is known regarding the molecular function of hYKL-39 in joint homeostasis. Sequence analyses indicated that hYKL-39 has significant identity with the human chitotorisidase family molecules, although it is considered that hYKL-39 has no enzymatic activity since it lacks putative chitinase catalytic motif. In this study, to examine the molecular function of hYKL-39 in chondrocytes, we overexpressed hYKL-39 in ATDC5 cells. Here we report that hYKL-39 enhances colony forming activity, cell proliferation, and type II collagen expression in these cells. These data suggest that hYKL-39 is a novel growth and differentiation factor involved in cartilage homeostasis.

  16. Cultura Política na Antiguidade

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    José Petrúcio Farias Júnior

    2009-06-01

    Full Text Available

    Pretendemos discutir nesse artigo algumas implicações do termo cultura política na Antiguidade, especificamente, na sociedade romana imperial. Dessa forma, acreditamos que as considerações que apresentaremos a seguir contribuam para reflexão da utilização desse termo, produto das investigações contemporâneas, sobre os estudos das sociedades antigas. Para a historiadora Profa. Dra. Margarida Maria de Carvalho, tais reflexões representam ainda uma lacuna na historiografia concernente a essa temática. Isso posto, discorreremos, inicialmente, sobre o conceito de cultura e seus desdobramentos para, em seguida, refletirmos sobre o viés interpretativo que fundamenta estudos históricos que se desenvolvem sob o beneplácito da linha de pesquisa intitulada História e Cultura Política.

  17. Adeus à política

    Directory of Open Access Journals (Sweden)

    Manoel Mendonça Filho

    2012-01-01

    Full Text Available O artigo trata as questões do "Estado" e da "Política" partindo do exemplo concreto do processo de institucionalização, no Brasil, de práticas profissionais em psicologia reconhecidas como Análise Institucional (vertente grupalista francesa consideravelmente difundida nos últimos 20 anos. Trabalho para expor uma face menos visível da judicialização que funciona ao nível das concepções, crenças e valores entre os operadores dos equipamentos onde se materializam as políticas públicas engendradas pelo excesso legalista. Dentre as modalidades desse apego à lei, toma-se em análise aquela mais próxima de nossas práticas de funcionalismo público marcando o índice de grau máximo de sua institucionalização: a aceitação consensual da competência como critério de legitimidade na operação dos "instrumentos da violência institucional".

  18. Política de los intelectuales

    Directory of Open Access Journals (Sweden)

    Todorov Tzevetan

    1998-06-01

    Full Text Available ¿Qué es un intelectual? Por lo que a mi respecta, limito el uso de este término de la siguiente manera: es un estudioso o un artista (categoria que incluye a los escritores que no se contenta con realizar trabajos cientificos o con la creación de una obra de arte, que no se contenta, por lo tanto, con una méra búsqueda de lo verdadero y con un méro desarrollo de lo bello, sino que siente asimismo comprometido con la noción de bienestar público, con los valores de la sociedad en la que vive, es alguien que participa en el debate sobre esos mismos valores. El intelectual así entendido se halla muy lejos del artista o del estudioso a quienes no preocupan en absoluto las dimensiones políticas o éticas de sus obras; muy lejos también, del predicador o del político profesional, que no crean obra alguna.

  19. Transient expression and activity of human DNA polymerase iota in loach embryos.

    Science.gov (United States)

    Makarova, Irina V; Kazakov, Andrey A; Makarova, Alena V; Khaidarova, Nella V; Kozikova, Larisa V; Nenasheva, Valentina V; Gening, Leonid V; Tarantul, Vyacheslav Z; Andreeva, Ludmila E

    2012-02-01

    Human DNA polymerase iota (Pol ι) is a Y-family DNA polymerase with unusual biochemical properties and not fully understood functions. Pol ι preferentially incorporates dGTP opposite template thymine. This property can be used to monitor Pol ι activity in the presence of other DNA polymerases, e.g. in cell extracts of tissues and tumors. We have now confirmed the specificity and sensitivity of the method of Pol ι activity detection in cell extracts using an animal model of loach Misgurnus fossilis embryos transiently expressing human Pol ι. The overexpression of Pol ι was shown to be accompanied by an increase in abnormalities in development and the frequency of pycnotic nuclei in fish embryos. Further analysis of fish embryos with constitutive or regulated Pol ι expression may provide insights into Pol ι functions in vertebrate animals.

  20. Las rentas de las exportaciones y la política comercial con oligopolio

    Directory of Open Access Journals (Sweden)

    Marcos Ávalos

    2005-01-01

    Full Text Available Para una industria oligopólica, este ensayo analiza la manera cómo la políti -ca comercial puede depender de la naturaleza competitiva de los mercados.Estudiamos los efectos de las fusiones nacionales y extranjeras en la políticaco mer cial óp ti ma del país de re fe ren cia y en las ren tas de las ex por ta cio nes yel bienestar interno. Hay cuatro resultados principales: i se de mues tra quesi el país de referencia aplica su política comercial óptima, siempre perderáa resultas de una fusión extranje ra; ii cuan do el país de re fe ren cia apli ca supolítica comercial óptima, una fusión extranjera disminuirá las rentas de lasexportaciones; iii cuando el gobierno responde óptimamente a una fusióninterna, ésta no afectará el bienestar nacional, y iv cuan do el go bier no res -pon de óp ti ma men te a una fu sión in ter na, ésta no afec ta rá las ren tas de lasexportaciones.

  1. Investigation of Virtual Digital Human and Robotic Device Technology Merger Complimented by Haptics and Autostereoscopic Displays, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — As expected, the STTR Phase I investigation confirmed that the Digital Virtual Human (DVH) and Robonaut technologies can be merged, and that haptic and...

  2. Historia del Pensamiento Político Premoderno 05 Fin de la polis. Alejandro Magno

    OpenAIRE

    Sanz Díaz, Benito

    2010-01-01

    Tema 5 El fin de la polis y el surgimiento de nuevas escuelas filosóficas 1.- El declive de la polis griega 2.- Transformación, decadencia y fin de las polis griegas 3.- Filipo II de Macedonia 4.- Alejandro Magno 5.- Helenismo y nuevas concepciones políticas 6.- Epicureismo. Epicuro de Samos 7.- Los cínicos. Ni hogar ni patria, ni ciudad ni ley 8.- El estoicismo. El estoico es un ciudadano del mundo. El cosmopolitismo. La stoa 9.- Las Meditaciones de Marco Aurel...

  3. Economía Política I, 2010-11

    OpenAIRE

    Antón Pérez, José Ignacio

    2010-01-01

    I. Materiales de clase: Teoría: 0. Conceptos básicos; 1. El problema económico; 2. Las ganancias derivadas del comercio; 3. Elementos básicos de la oferta y la demanda; 4. Elasticidades; 5. La medición del bienestar y la política económica; 6. La empresa: producción, costes y beneficios; 7. Las empresas en los mercados competitivos; Ejercicios: Ejercicios del Tema 2; Ejercicios del Tema 3; Ejercicios del Tema 4; Ejercicios del Tema 5; Ejercicios del Tema 6 y 7; Ejercicios de Repaso. II. Bibli...

  4. Development of safety and regulatory requirements for Korean next generation reactor - Development of human factors design review guidelines (II)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Lee, Hyun Chul; Cheon, Se Woo [Korea Atomic Energy Research Institute, Taejon (Korea)

    1999-02-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25. Human Factors Engineering Program Review Model' and '26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and the characteristics of the KNGR design, and reviewing the reference documents of NURGE-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides at KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system design review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we updated the guidelines by reviewing the literature related to alarm design that published after 1994. 12 refs., 11 figs., 2 tabs. (Author)

  5. An analysis of the human reliability on Three Mile Island II accident considering THERP and ATHEANA methodologies

    International Nuclear Information System (INIS)

    Fonseca, Renato Alves da; Alvim, Antonio Carlos Marques

    2005-01-01

    The research on the Analysis of the Human Reliability becomes more important every day, as well as the study of the human factors and the contributions of the same ones to the incidents and accidents, mainly in complex plants or of high technology. The analysis here developed it uses the methodologies THERP (Technique for Human Error Prediction) and ATHEANA (A Technique for Human Error Analysis), as well as, the tables and the cases presented in THERP Handbook and to develop a qualitative and quantitative study of an occurred nuclear accident. The chosen accident was it of Three Mile Island (TMI). The accident analysis has revealed a series of incorrect actions that resulted in the permanent loss of the reactor and shutdown of Unit 2. This study also aims at enhancing the understanding of the THERP and ATHEANA methods and at practical applications. In addition, it is possible to understand the influence of plant operational status on human failures and the influence of human failures on equipment of a system, in this case, a nuclear power plant. (author)

  6. Development of safety and regulatory requirements for Korean next generation reactor - Development of human factors design review guidelines (II)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Lee, Hyun Chul; Cheon, Se Woo [Korea Atomic Energy Research Institute, Taejon (Korea)

    1999-02-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25. Human Factors Engineering Program Review Model' and '26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and the characteristics of the KNGR design, and reviewing the reference documents of NURGE-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides at KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system design review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we updated the guidelines by reviewing the literature related to alarm design that published after 1994. 12 refs., 11 figs., 2 tabs. (Author)

  7. Judicialização da política e Sistema Interamericano de Direitos Humanos: uma investigação empírica da atuação das organizações da sociedade civil / Judicialization of Politics and Inter-American Human Rights system

    Directory of Open Access Journals (Sweden)

    Carolina Alves Vestena

    2011-09-01

    ção destes mecanismos de controle social pela sociedade civil organizada. Palavras-chave: Sistema Interamericano de Direitos Humanos, Judicialização da Política, Pesquisa Empírica, Organizações não governamentais. Abstract This article brings analysis on the third stage of the research lead by the group Human Rights, Judiciary and Society – DHPJS (in portuguese – about the justice system and the performance of its agents in Rio de Janeiro. Its focus is set on the usage of international human rights laws by national courts. During previous stages, judges (both of district and circuit courts were interviewed and asked about the usage of such norms in their decision-making process and about their education on the theme. This time, attention is brought to those recurring to the system, especially when organized collectively in civil associations. Our hypothesis sustains that judicial courts have been looked for as locations for disputes, both in an internal perspective (which may be proved by many theoretical outlooks as in an international one. The phenomenon identified in the national arena can be interpreted in the context of regional protection system for Human Rights: the Inter-American Court and Commission may be developing into a “para-judicial” stage in the concretization of those rights. This second hypothesis may be spoken of theoretically and proven empirically so as to check if civil organizations are used to turning their social struggles into cases before the mentioned system. The empirical research lead by the group supplies data for reflections on the hypothesis aside from showing threads to pursue. The group talked to 36 NGOs registered on ABONG – Brazilian Association of Non-Governmental Organizations –who aim at Human Rights protection so as to gather information on their articulation with both the national justice system and the regional one. The article presents possible connections between judicialization of politics and the regional

  8. Stimulation of Pol III-dependent 5S rRNA and U6 snRNA gene expression by AP-1 transcription factors.

    Science.gov (United States)

    Ahuja, Richa; Kumar, Vijay

    2017-07-01

    RNA polymerase III transcribes structurally diverse group of essential noncoding RNAs including 5S ribosomal RNA (5SrRNA) and U6 snRNA. These noncoding RNAs are involved in RNA processing and ribosome biogenesis, thus, coupling Pol III activity to the rate of protein synthesis, cell growth, and proliferation. Even though a few Pol II-associated transcription factors have been reported to participate in Pol III-dependent transcription, its activation by activator protein 1 (AP-1) factors, c-Fos and c-Jun, has remained unexplored. Here, we show that c-Fos and c-Jun bind to specific sites in the regulatory regions of 5S rRNA (type I) and U6 snRNA (type III) gene promoters and stimulate their transcription. Our chromatin immunoprecipitation studies suggested that endogenous AP-1 factors bind to their cognate promoter elements during the G1/S transition of cell cycle apparently synchronous with Pol III transcriptional activity. Furthermore, the interaction of c-Jun with histone acetyltransferase p300 promoted the recruitment of p300/CBP complex on the promoters and facilitated the occupancy of Pol III transcriptional machinery via histone acetylation and chromatin remodeling. The findings of our study, together, suggest that AP-1 factors are novel regulators of Pol III-driven 5S rRNA and U6 snRNA expression with a potential role in cell proliferation. © 2017 Federation of European Biochemical Societies.

  9. O conceito de liberdade política em Montesquieu

    Directory of Open Access Journals (Sweden)

    Maria Beatriz Nizza da Silva

    1969-06-01

    Full Text Available O primeiro passo na análise do conceito de liberdade política, tal como êle se nos apresenta em De l'esprit des lois, deverá assina-lar uma diferença, fundamental para Montesquieu, entre "liberdade filosófica" e "liberdade política".

  10. Los spots factor, esencial del marketing político

    Directory of Open Access Journals (Sweden)

    María de Jesús Origel Gutiérrez

    2000-01-01

    Full Text Available EI objetivo del presente trabajo es demostrar que en las elecciones presidenciales de julio de 2000, la forma de hacer política en México se modificó al introducir en las campanas electorales el marketing político y nuevas estrategias de comunicación, en especial los spots televisivos

  11. As armadilhas do tripé da política macroeconômica brasileira

    Directory of Open Access Journals (Sweden)

    ANDRÉ NASSIF

    2015-09-01

    Full Text Available RESUMOEste artigo analisa o chamado tripé da política macroeconômica brasileira, que desde 1999 tem combinado um regime de metas de inflação, um regime de taxa de câmbio flutuante e metas de superávit fiscal primário. A menos que o seu modus operandi seja alterado, o tripé não será capaz de libertar a economia brasileira de outra "possível trindade": altas taxas de juros reais, a apreciação da taxa de câmbio real e crescimento econômico muito baixo. Depois de analisar brevemente a base teórica sob o tripé macroeconômico, o artigo mostra por que este regime de política macroeconômica, se avaliado numa perspectiva de longo ou médio prazo, não tem sido capaz de garantir a estabilidade dos preços nem o crescimento econômico. Além da sugestão de romper com a estratégia brasileira de crescer com poupança externa, o documento também sugere três principais formas de mudar o modus operandi do tripé brasileiro: i aumentar o horizonte de tempo para atingir a meta de inflação, como tem sido o experiência da maioria dos países que adotam esse regime de política monetária; ii restaurar o papel anticíclico da política fiscal brasileira; e iii adotar uma combinação de mecanismos que visem prevenir que a moeda brasileira entre em uma nova tendência cíclica da apreciação em termos reais.

  12. Nhe I and Hinc II polymorphisms in the human laminin B1 chain gene on 7q22

    Energy Technology Data Exchange (ETDEWEB)

    Pikkarainen, T; Savolainen, E R; Tryggvason, K [Univ. of Oulu (Finland)

    1989-06-12

    pHL-40 and pHL-42 are overlapping cDNA clones that code for 4.2 kb of the 3{prime} end of the 5.5 kb mRNA. Nhe I detects a two allele polymorphism with fragments of 4.3 kb or 4.0 kb and an invariant band of 10.0 kb. Hinc II detects a two allele polymorphism with fragments of 6.6 kb or 5.5 kb and 1.1 kb and invariant bands of 7.8 kb, 4.0 kb, 3.3 kb, 2.3 kb and 0.6 kb. The allele frequency was studied in 60 chromosomes of unrelated Finnish individuals. The probe was localized to chromosome 7q22 by somatic cell and in situ hybridization. Co-dominant inheritance of the Nhe I RFLP was shown in one family and of the Hinc II RFLP in five families.

  13. NNDSS - Table II. Vibriosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Vibriosis - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year), and selected...

  14. NNDSS - Table II. Vibriosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Vibriosis - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year), and selected...

  15. Stimulation of the Angiotensin II AT2 Receptor is Anti-inflammatory in Human Lipopolysaccharide-Activated Monocytic Cells

    DEFF Research Database (Denmark)

    Menk, Mario; Graw, Jan Adriaan; von Haefen, Clarissa

    2015-01-01

    and the translational level over course of time. Treatment with C21 attenuated the expression of TNFα, IL-6, and IL-10 after LPS challenge in both cell lines in a time- and dose-dependent manner. We conclude that selective AT2 receptor stimulation acts anti-inflammatory in human monocytes. Modulation of cytokine......Recently, AT2 receptors have been discovered on the surface of human immunocompetent cells such as monocytes. Data on regulative properties of this receptor on the cellular immune response are poor. We hypothesized that direct stimulation of the AT2 receptor mediates anti-inflammatory responses...... in these cells. Human monocytic THP-1 and U937 cells were stimulated with lipopolysaccharide (LPS) and the selective AT2 receptor agonist Compound 21 (C21). Expression of pro- and anti-inflammatory cytokines IL-6, IL-10, tumor necrosis factor-α (TNFα), and IL-1β were analyzed on both the transcriptional...

  16. Política digital: El uso de Facebook en política electoral en Costa Rica (II

    Directory of Open Access Journals (Sweden)

    Roberto Cruz Romero

    2017-07-01

    Full Text Available Se presenta una continuación al trabajo realizado sobre el uso de Internet en procesos electorales, trazando paralelismos y subrayando las diferencias que subyacen entre la significancia simbólica de una elección presidencial y las elecciones municipales para la ciudadanía. Nuevamente, se recurre a un análisis del comportamiento en redes sociales, Facebook específicamente, y un análisis contextual de la realidad sociopolítica percibida en las distintas localidades, y en cada partido. Se estudiaron 26 partidos inscritos solamente a escala cantonal, y se profundizó en los casos de cinco partidos cantonales que obtuvieron la victoria en la respectiva alcaldía. Esto respalda y robustece la línea de investigación que desde el Programa Sociedad de la Información y el Conocimiento (PROSIC se ha trabajado, en aras de presentar el potencial de la tecnología en la democracia, como un elemento más en la construcción de una sociedad basada en la información y el conocimiento

  17. Survey of Current US Army POL Doctrine, Procedures, Personnel, and Equipment for the Supply and Inland Distribution of Bulk POL

    Science.gov (United States)

    1985-10-01

    Refueling Under Armor ......................... 34 Page i ,t .J APPENDICES A. POL Unit Missions and Capabilities ....................... A-I B. Roster...refueling Open versus closed port refueling Requirement for Refueling Under Armor Robotic refueler V % Page 34 S.< ’p. ". APPgeDI A-"" • " ’ ’ POL " it

  18. A política da Igreja Universal e seus reflexos nos campos religioso e político brasileiros

    Directory of Open Access Journals (Sweden)

    Oro Ari Pedro

    2003-01-01

    Full Text Available Este texto versa sobre a inserção da Igreja Universal do Reino de Deus (IURD na política nacional e seus efeitos nos campos religioso e político. Em razão da eficácia de seu carisma institucional, a Universal procedeu, dentro do próprio grupo religioso, a uma ressemantização do ato de votar em particular e da percepção da política em geral, inscrevendo-os em sua lógica religiosa. Isso é uma importante chave explicativa para o elevado grau de fidelidade de votos e o êxito político cada vez maior constatado nas últimas eleições. Ademais, a prática política da Universal está produzindo um efeito mimético em outra igrejas evangélicas, que tendem a imitar seu modelo de fazer política. Sua inserção política, sobretudo por intermédio do Partido Liberal, não passa despercebida pelos partidos, constituindo-se, assim, em um ator relevante na atual conjuntura política brasileira.

  19. Why is Organizing Human Resource Development so Problematic? Perspectives from the Learning-Network Theory (Part II)

    Science.gov (United States)

    Poell, Rob F.; Van Der Krogt, Ferd

    2017-01-01

    Purpose: Human resource development (HRD) is an important field within management. Developing employees is often regarded as an instrument to improve the internal labor market and support organizational change. Organizing HRD to these ends, however, is frequently a problematic affair, in terms of training effectiveness, participant motivation and…

  20. Why is organizing human resource development so problematic? : Perspectives from the learning-network theory (Part II)

    NARCIS (Netherlands)

    Poell, R.F.; van der Krogt, F.J.

    2017-01-01

    Purpose Human resource development (HRD) is an important field within management. Developing employees is often regarded as an instrument to improve the internal labor market and support organizational change. Organizing HRD to these ends, however, is frequently a problematic affair, in terms of