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Sample records for dead box protein

  1. Structure of the Yeast DEAD box protein Mss116p reveals two wedges that crimp RNA.

    Science.gov (United States)

    Del Campo, Mark; Lambowitz, Alan M

    2009-09-11

    The yeast DEAD box protein Mss116p is a general RNA chaperone that functions in mitochondrial group I and II intron splicing, translational activation, and RNA end processing. Here we determined high-resolution X-ray crystal structures of Mss116p complexed with an RNA oligonucleotide and ATP analogs AMP-PNP, ADP-BeF(3)(-), or ADP-AlF(4)(-). The structures show the entire helicase core acting together with a functionally important C-terminal extension. In all structures, the helicase core is in a closed conformation with a wedge alpha helix bending RNA 3' of the central bound nucleotides, as in previous DEAD box protein structures. Notably, Mss116p's C-terminal extension also bends RNA 5' of the central nucleotides, resulting in RNA crimping. Despite reported functional differences, we observe few structural changes in ternary complexes with different ATP analogs. The structures constrain models of DEAD box protein function and reveal a strand separation mechanism in which a protein uses two wedges to act as a molecular crimper.

  2. A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev

    International Nuclear Information System (INIS)

    HIV-1 Rev escorts unspliced viral mRNAs out of the nucleus of infected cells, which allows formation of infectious HIV-1 virions. We have identified a putative DEAD box (Asp-Glu-Ala-Asp) RNA helicase, DDX1, as a cellular co-factor of Rev, through yeast and mammalian two-hybrid systems using the N-terminal motif of Rev as 'bait'. DDX1 is not a functional homolog of HIV-1 Rev, but down-regulation of DDX1 resulted in an alternative splicing pattern of Rev-responsive element (RRE)-containing mRNA, and attenuation of Gag p24 antigen production from HLfb rev(-) cells rescued by exogenous Rev. Co-transfection of a DDX1 expression vector with HIV-1 significantly increased viral production. DDX1 binding to Rev, as well as to the RRE, strongly suggest that DDX1 affects Rev function through the Rev-RRE axis. Moreover, down-regulation of DDX1 altered the steady state subcellular distribution of Rev, from nuclear/nucleolar to cytoplasmic dominance. These findings indicate that DDX1 is a critical cellular co-factor for Rev function, which maintains the proper subcellular distribution of this lentiviral regulatory protein. Therefore, alterations in DDX1-Rev interactions could induce HIV-1 persistence and targeting DDX1 may lead to rationally designed and novel anti-HIV-1 strategies and therapeutics

  3. The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor

    Science.gov (United States)

    Bates, Gaynor J; Nicol, Samantha M; Wilson, Brian J; Jacobs, Anne-Marie F; Bourdon, Jean-Christophe; Wardrop, Julie; Gregory, David J; Lane, David P; Perkins, Neil D; Fuller-Pace, Frances V

    2005-01-01

    The DEAD box RNA helicase, p68, has been implicated in various cellular processes and has been shown to possess transcriptional coactivator function. Here, we show that p68 potently synergises with the p53 tumour suppressor protein to stimulate transcription from p53-dependent promoters and that endogenous p68 and p53 co-immunoprecipitate from nuclear extracts. Strikingly, RNAi suppression of p68 inhibits p53 target gene expression in response to DNA damage, as well as p53-dependent apoptosis, but does not influence p53 stabilisation or expression of non-p53-responsive genes. We also show, by chromatin immunoprecipitation, that p68 is recruited to the p21 promoter in a p53-dependent manner, consistent with a role in promoting transcriptional initiation. Interestingly, p68 knock-down does not significantly affect NF-κB activation, suggesting that the stimulation of p53 transcriptional activity is not due to a general transcription effect. This study represents the first report of the involvement of an RNA helicase in the p53 response, and highlights a novel mechanism by which p68 may act as a tumour cosuppressor in governing p53 transcriptional activity. PMID:15660129

  4. Structure of the SPRY domain of the human RNA helicase DDX1, a putative interaction platform within a DEAD-box protein

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    Kellner, Julian N.; Meinhart, Anton, E-mail: anton.meinhart@mpimf-heidelberg.mpg.de [Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg (Germany)

    2015-08-25

    The structure of the SPRY domain of the human RNA helicase DDX1 was determined at 2.0 Å resolution. The SPRY domain provides a putative protein–protein interaction platform within DDX1 that differs from other SPRY domains in its structure and conserved regions. The human RNA helicase DDX1 in the DEAD-box family plays an important role in RNA processing and has been associated with HIV-1 replication and tumour progression. Whereas previously described DEAD-box proteins have a structurally conserved core, DDX1 shows a unique structural feature: a large SPRY-domain insertion in its RecA-like consensus fold. SPRY domains are known to function as protein–protein interaction platforms. Here, the crystal structure of the SPRY domain of human DDX1 (hDSPRY) is reported at 2.0 Å resolution. The structure reveals two layers of concave, antiparallel β-sheets that stack onto each other and a third β-sheet beneath the β-sandwich. A comparison with SPRY-domain structures from other eukaryotic proteins showed that the general β-sandwich fold is conserved; however, differences were detected in the loop regions, which were identified in other SPRY domains to be essential for interaction with cognate partners. In contrast, in hDSPRY these loop regions are not strictly conserved across species. Interestingly, though, a conserved patch of positive surface charge is found that may replace the connecting loops as a protein–protein interaction surface. The data presented here comprise the first structural information on DDX1 and provide insights into the unique domain architecture of this DEAD-box protein. By providing the structure of a putative interaction domain of DDX1, this work will serve as a basis for further studies of the interaction network within the hetero-oligomeric complexes of DDX1 and of its recruitment to the HIV-1 Rev protein as a viral replication factor.

  5. Crystallization and preliminary X-ray diffraction of the DEAD-box protein Mss116p complexed with an RNA oligonucleotide and AMP-PNP

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    Del Campo, Mark; Lambowitz, Alan M.; (Texas)

    2009-09-02

    The Saccharomyces cerevisiae DEAD-box protein Mss116p is a general RNA chaperone which functions in mitochondrial group I and group II intron splicing, translation and RNA-end processing. For crystallization trials, full-length Mss116p and a C-terminally truncated protein (Mss116p/{Delta}598-664) were overproduced in Escherichia coli and purified to homogeneity. Mss116p exhibited low solubility in standard solutions ({le}1 mg ml{sup -1}), but its solubility could be increased by adding 50 mM L-arginine plus 50 mM L-glutamate and 50% glycerol to achieve concentrations of {approx}10 mg ml{sup -1}. Initial crystals were obtained by the microbatch method in the presence of a U{sub 10} RNA oligonucleotide and the ATP analog AMP-PNP and were then improved by using seeding and sitting-drop vapor diffusion. A cryocooled crystal of Mss116p/{Delta}598-664 in complex with AMP-PNP and U{sub 10} belonged to space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 88.54, b = 126.52, c = 55.52 {angstrom}, and diffracted X-rays to beyond 1.9 {angstrom} resolution using synchrotron radiation from sector 21 at the Advanced Photon Source.

  6. In vivo mapping of the functional regions of the DEAD-box helicase Vasa

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    Mehrnoush Dehghani

    2015-03-01

    Full Text Available The maternally expressed Drosophila melanogaster DEAD-box helicase Vasa (Vas is necessary for many cellular and developmental processes, including specification of primordial germ cells (pole cells, posterior patterning of the embryo, piRNA-mediated repression of transposon-encoded mRNAs, translational activation of gurken (grk mRNA, and completion of oogenesis itself. Vas protein accumulates in the perinuclear nuage in nurse cells soon after their specification, and then at stage 10 Vas translocates to the posterior pole plasm of the oocyte. We produced a series of transgenic constructs encoding eGFP-Vas proteins carrying mutations affecting different regions of the protein, and analyzed in vivo which Vas functions each could support. We identified novel domains in the N- and C-terminal regions of the protein that are essential for localization, transposon repression, posterior patterning, and pole cell specification. One such functional region, the most C-terminal seven amino acids, is specific to Vas orthologues and is thus critical to distinguishing Vas from other closely related DEAD-box helicases. Surprisingly, we also found that many eGFP-Vas proteins carrying mutations that would be expected to abrogate DEAD-box helicase function localized to the nuage and posterior pole, and retained the capacity to support oogenesis, although they did not function in embryonic patterning, pole cell specification, grk activation, or transposon repression. We conclude from these experiments that Vas, a multifunctional protein, uses different domains and different molecular associations to carry out its various cellular and developmental roles.

  7. Motif III in superfamily 2 "helicases" helps convert the binding energy of ATP into a high-affinity RNA binding site in the yeast DEAD-box protein Ded1.

    Science.gov (United States)

    Banroques, Josette; Doère, Monique; Dreyfus, Marc; Linder, Patrick; Tanner, N Kyle

    2010-03-05

    Motif III in the putative helicases of superfamily 2 is highly conserved in both its sequence and its structural context. It typically consists of the sequence alcohol-alanine-alcohol (S/T-A-S/T). Historically, it was thought to link ATPase activity with a "helicase" strand displacement activity that disrupts RNA or DNA duplexes. DEAD-box proteins constitute the largest family of superfamily 2; they are RNA-dependent ATPases and ATP-dependent RNA binding proteins that, in some cases, are able to disrupt short RNA duplexes. We made mutations of motif III (S-A-T) in the yeast DEAD-box protein Ded1 and analyzed in vivo phenotypes and in vitro properties. Moreover, we made a tertiary model of Ded1 based on the solved structure of Vasa. We used Ded1 because it has relatively high ATPase and RNA binding activities; it is able to displace moderately stable duplexes at a large excess of substrate. We find that the alanine and the threonine in the second and third positions of motif III are more important than the serine, but that mutations of all three residues have strong phenotypes. We purified the wild-type and various mutants expressed in Escherichia coli. We found that motif III mutations affect the RNA-dependent hydrolysis of ATP (k(cat)), but not the affinity for ATP (K(m)). Moreover, mutations alter and reduce the affinity for single-stranded RNA and subsequently reduce the ability to disrupt duplexes. We obtained intragenic suppressors of the S-A-C mutant that compensate for the mutation by enhancing the affinity for ATP and RNA. We conclude that motif III and the binding energy of gamma-PO(4) of ATP are used to coordinate motifs I, II, and VI and the two RecA-like domains to create a high-affinity single-stranded RNA binding site. It also may help activate the beta,gamma-phosphoanhydride bond of ATP. (c) 2009 Elsevier Ltd. All rights reserved.

  8. Evolution of the DEAD box helicase family in chicken: chickens have no DHX9 ortholog.

    Science.gov (United States)

    Sato, Haruko; Oshiumi, Hiroyuki; Takaki, Hiromi; Hikono, Hirokazu; Seya, Tsukasa

    2015-10-01

    Viral RNA represents a pattern molecule that can be recognized by RNA sensors in innate immunity. Humans and mice possess cytoplasmic DNA/RNA sensors for detecting viral replication. There are a number of DEAD (Asp-Glu-Ala-Asp; DExD/H) box-type helicases in mammals, among which retinoic acid-inducible gene 1 (RIG-I) and melanoma differentiation-associated protein 5 (MDA50) are indispensable for RNA sensing; however, they are functionally supported by a number of sensors that directly bind viral RNA or replicative RNA intermediates to convey signals to RIG-I and MDA5. Some DEAD box helicase members recognize DNA irrespective of the origin. These sensors transmit IFN-inducing signals through adaptors, including mitochondrial antiviral signaling. Viral double-stranded RNAs are reportedly sensed by the helicases DDX1, DDX21, DHX36, DHX9, DDX3, DDX41, LGP2 and DDX60, in addition to RIG-I and MDA5, and induce type I IFNs, thereby blocking viral replication. Humans and mice have all nucleic acid sensors listed here. In the RNA sensing system in chicken, it was found in the present study that most DEAD box helicases are conserved; however, DHX9 is genetically deficient in addition to reported RIG-I. Based on the current genome databases, similar DHX9 deficiency was observed in ducks and several other bird species. Because chicken, but not duck, was found to be deficient in RIG-I, the RNA-sensing system of chicken lacks RIG-I and DHX9 and is thus more fragile than that of duck or mammal. DHX9 may generally compensate for the function of RIG-I and deficiency of DHX9 possibly participates in exacerbations of viral infection such as influenza in chickens. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

  9. Structural and functional analysis of the human spliceosomal DEAD-box helicase Prp28

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    Möhlmann, Sina [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany); Mathew, Rebecca [Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, 37077 Göttingen (Germany); Neumann, Piotr; Schmitt, Andreas [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany); Lührmann, Reinhard [Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, 37077 Göttingen (Germany); Ficner, Ralf, E-mail: rficner@uni-goettingen.de [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany)

    2014-06-01

    The crystal structure of the helicase domain of the human spliceosomal DEAD-box protein Prp28 was solved by SAD. The binding of ADP and ATP by Prp28 was studied biochemically and analysed with regard to the crystal structure. The DEAD-box protein Prp28 is essential for pre-mRNA splicing as it plays a key role in the formation of an active spliceosome. Prp28 participates in the release of the U1 snRNP from the 5′-splice site during association of the U5·U4/U6 tri-snRNP, which is a crucial step in the transition from a pre-catalytic spliceosome to an activated spliceosome. Here, it is demonstrated that the purified helicase domain of human Prp28 (hPrp28ΔN) binds ADP, whereas binding of ATP and ATPase activity could not be detected. ATP binding could not be observed for purified full-length hPrp28 either, but within an assembled spliceosomal complex hPrp28 gains ATP-binding activity. In order to understand the structural basis for the ATP-binding deficiency of isolated hPrp28, the crystal structure of hPrp28ΔN was determined at 2.0 Å resolution. In the crystal the helicase domain adopts a wide-open conformation, as the two RecA-like domains are extraordinarily displaced from the productive ATPase conformation. Binding of ATP is hindered by a closed conformation of the P-loop, which occupies the space required for the γ-phosphate of ATP.

  10. A Cold-Inducible DEAD-Box RNA Helicase from Arabidopsis thaliana Regulates Plant Growth and Development under Low Temperature.

    Science.gov (United States)

    Liu, Yuelin; Tabata, Daisuke; Imai, Ryozo

    2016-01-01

    DEAD-box RNA helicases comprise a large family and are involved in a range of RNA processing events. Here, we identified one of the Arabidopsis thaliana DEAD-box RNA helicases, AtRH7, as an interactor of Arabidopsis COLD SHOCK DOMAIN PROTEIN 3 (AtCSP3), which is an RNA chaperone involved in cold adaptation. Promoter:GUS transgenic plants revealed that AtRH7 is expressed ubiquitously and that its levels of the expression are higher in rapidly growing tissues. Knockout mutant lines displayed several morphological alterations such as disturbed vein pattern, pointed first true leaves, and short roots, which resemble ribosome-related mutants of Arabidopsis. In addition, aberrant floral development was also observed in rh7 mutants. When the mutants were germinated at low temperature (12°C), both radicle and first leaf emergence were severely delayed; after exposure of seedlings to a long period of cold, the mutants developed aberrant, fewer, and smaller leaves. RNA blots and circular RT-PCR revealed that 35S and 18S rRNA precursors accumulated to higher levels in the mutants than in WT under both normal and cold conditions, suggesting the mutants are partially impaired in pre-rRNA processing. Taken together, the results suggest that AtRH7 affects rRNA biogenesis and plays an important role in plant growth under cold.

  11. A Cold-Inducible DEAD-Box RNA Helicase from Arabidopsis thaliana Regulates Plant Growth and Development under Low Temperature.

    Directory of Open Access Journals (Sweden)

    Yuelin Liu

    Full Text Available DEAD-box RNA helicases comprise a large family and are involved in a range of RNA processing events. Here, we identified one of the Arabidopsis thaliana DEAD-box RNA helicases, AtRH7, as an interactor of Arabidopsis COLD SHOCK DOMAIN PROTEIN 3 (AtCSP3, which is an RNA chaperone involved in cold adaptation. Promoter:GUS transgenic plants revealed that AtRH7 is expressed ubiquitously and that its levels of the expression are higher in rapidly growing tissues. Knockout mutant lines displayed several morphological alterations such as disturbed vein pattern, pointed first true leaves, and short roots, which resemble ribosome-related mutants of Arabidopsis. In addition, aberrant floral development was also observed in rh7 mutants. When the mutants were germinated at low temperature (12°C, both radicle and first leaf emergence were severely delayed; after exposure of seedlings to a long period of cold, the mutants developed aberrant, fewer, and smaller leaves. RNA blots and circular RT-PCR revealed that 35S and 18S rRNA precursors accumulated to higher levels in the mutants than in WT under both normal and cold conditions, suggesting the mutants are partially impaired in pre-rRNA processing. Taken together, the results suggest that AtRH7 affects rRNA biogenesis and plays an important role in plant growth under cold.

  12. microRNAs targeting DEAD-box helicases are involved in salinity stress response in rice (Oryza sativa L.

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    Macovei Anca

    2012-10-01

    Full Text Available Abstract Background Rice (Oryza sativa L., one of the most important food crop in the world, is considered to be a salt-sensitive crop. Excess levels of salt adversely affect all the major metabolic activities, including cell wall damage, cytoplasmic lysis and genomic stability. In order to cope with salt stress, plants have evolved high degrees of developmental plasticity, including adaptation via cascades of molecular networks and changes in gene expression profiles. Posttranscriptional regulation, through the activity of microRNAs, also plays an important role in the plant response to salinity conditions. MicroRNAs are small endogenous RNAs that modulate gene expression and are involved in the most essential physiological processes, including plant development and adaptation to environmental changes. Results In the present study, we investigated the expression profiles of osa-MIR414, osa-MIR408 and osa-MIR164e along with their targeted genes, under salinity stress conditions in wild type and transgenic rice plants ectopically expressing the PDH45 (Pea DNA Helicase gene. The present miRNAs were predicted to target the OsABP (ATP-Binding Protein, OsDSHCT (DOB1/SK12/helY-like DEAD-box Helicase and OsDBH (DEAD-Box Helicase genes, included in the DEAD-box helicase family. An in silico characterization of the proteins was performed and the miRNAs predicted targets were validated by RLM-5′RACE. The qRT-PCR analysis showed that the OsABP, OsDBH and OsDSHCT genes were up-regulated in response to 100 and 200 mM NaCl treatments. The present study also highlighted an increased accumulation of the gene transcripts in wild type plants, with the exception of the OsABP mRNA which showed the highest level (15.1-fold change compared to control in the transgenic plants treated with 200 mM NaCl. Salinity treatments also affected the expression of osa-MIR414, osa-MIR164e and osa-MIR408, found to be significantly down-regulated, although the changes in mi

  13. microRNAs targeting DEAD-box helicases are involved in salinity stress response in rice (Oryza sativa L.).

    Science.gov (United States)

    Macovei, Anca; Tuteja, Narendra

    2012-10-08

    Rice (Oryza sativa L.), one of the most important food crop in the world, is considered to be a salt-sensitive crop. Excess levels of salt adversely affect all the major metabolic activities, including cell wall damage, cytoplasmic lysis and genomic stability. In order to cope with salt stress, plants have evolved high degrees of developmental plasticity, including adaptation via cascades of molecular networks and changes in gene expression profiles. Posttranscriptional regulation, through the activity of microRNAs, also plays an important role in the plant response to salinity conditions. MicroRNAs are small endogenous RNAs that modulate gene expression and are involved in the most essential physiological processes, including plant development and adaptation to environmental changes. In the present study, we investigated the expression profiles of osa-MIR414, osa-MIR408 and osa-MIR164e along with their targeted genes, under salinity stress conditions in wild type and transgenic rice plants ectopically expressing the PDH45 (Pea DNA Helicase) gene. The present miRNAs were predicted to target the OsABP (ATP-Binding Protein), OsDSHCT (DOB1/SK12/helY-like DEAD-box Helicase) and OsDBH (DEAD-Box Helicase) genes, included in the DEAD-box helicase family. An in silico characterization of the proteins was performed and the miRNAs predicted targets were validated by RLM-5'RACE. The qRT-PCR analysis showed that the OsABP, OsDBH and OsDSHCT genes were up-regulated in response to 100 and 200 mM NaCl treatments. The present study also highlighted an increased accumulation of the gene transcripts in wild type plants, with the exception of the OsABP mRNA which showed the highest level (15.1-fold change compared to control) in the transgenic plants treated with 200 mM NaCl. Salinity treatments also affected the expression of osa-MIR414, osa-MIR164e and osa-MIR408, found to be significantly down-regulated, although the changes in miRNA expression were limited. Osa-MIR414, osa-MIR164

  14. DDX4 (DEAD box polypeptide 4) colocalizes with cancer stem cell marker CD133 in ovarian cancers

    International Nuclear Information System (INIS)

    Kim, Ki Hyung; Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun; Moon, Soo Hyun; Suh, Dong Soo; Yoon, Man Soo; Park, Eun-Sil; Jeong, Namkung; Eo, Wan-Kyu; Kim, Heung Yeol; Cha, Hee-Jae

    2014-01-01

    Highlights: • Germ cell marker DDX4 was significantly increased in ovarian cancer. • Ovarian cancer stem cell marker CD133 was significantly increased in ovarian cancer. • DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. • CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4. • Germ cell marker DDX4 has the potential of ovarian cancer stem cell marker. - Abstract: DDX4 (DEAD box polypeptide 4), characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), is an RNA helicase which is implicated in various cellular processes involving the alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. DDX4 is known to be a germ cell-specific protein and is used as a sorting marker of germline stem cells for the production of oocytes. A recent report about DDX4 in ovarian cancer showed that DDX4 is overexpressed in epithelial ovarian cancer and disrupts a DNA damage-induced G2 checkpoint. We investigated the relationship between DDX4 and ovarian cancer stem cells by analyzing the expression patterns of DDX4 and the cancer stem cell marker CD133 in ovarian cancers via tissue microarray. Both DDX4 and CD133 were significantly increased in ovarian cancer compared to benign tumors, and showed similar patterns of expression. In addition, DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. Furthermore, almost all CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4, suggesting a strong possibility that DDX4 plays an important role in cancer stem cells, and/or can be used as an ovarian cancer stem cell marker

  15. DDX4 (DEAD box polypeptide 4) colocalizes with cancer stem cell marker CD133 in ovarian cancers

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    Kim, Ki Hyung [Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan (Korea, Republic of); Biomedical Research Institute and Pusan Cancer Center, Pusan National University Hospital, Busan (Korea, Republic of); Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun [Department of Parasitology and Genetics, Kosin University College of Medicine, Busan (Korea, Republic of); Moon, Soo Hyun; Suh, Dong Soo; Yoon, Man Soo [Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan (Korea, Republic of); Biomedical Research Institute and Pusan Cancer Center, Pusan National University Hospital, Busan (Korea, Republic of); Park, Eun-Sil [Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, MA (United States); Jeong, Namkung [Department of Obstetrics and Gynecology, The Catholic University, Seoul (Korea, Republic of); Eo, Wan-Kyu [Department of Internal Medicine, Kyung Hee University, Seoul (Korea, Republic of); Kim, Heung Yeol, E-mail: hykyale@yahoo.com [Department of Obstetrics and Gynecology, Kosin University College of Medicine, Busan (Korea, Republic of); Cha, Hee-Jae, E-mail: hcha@kosin.ac.kr [Department of Parasitology and Genetics, Kosin University College of Medicine, Busan (Korea, Republic of); Institute for Medical Science, Kosin University College of Medicine, Busan (Korea, Republic of)

    2014-05-02

    Highlights: • Germ cell marker DDX4 was significantly increased in ovarian cancer. • Ovarian cancer stem cell marker CD133 was significantly increased in ovarian cancer. • DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. • CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4. • Germ cell marker DDX4 has the potential of ovarian cancer stem cell marker. - Abstract: DDX4 (DEAD box polypeptide 4), characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), is an RNA helicase which is implicated in various cellular processes involving the alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. DDX4 is known to be a germ cell-specific protein and is used as a sorting marker of germline stem cells for the production of oocytes. A recent report about DDX4 in ovarian cancer showed that DDX4 is overexpressed in epithelial ovarian cancer and disrupts a DNA damage-induced G2 checkpoint. We investigated the relationship between DDX4 and ovarian cancer stem cells by analyzing the expression patterns of DDX4 and the cancer stem cell marker CD133 in ovarian cancers via tissue microarray. Both DDX4 and CD133 were significantly increased in ovarian cancer compared to benign tumors, and showed similar patterns of expression. In addition, DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. Furthermore, almost all CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4, suggesting a strong possibility that DDX4 plays an important role in cancer stem cells, and/or can be used as an ovarian cancer stem cell marker.

  16. Structural and biochemical analyses of the DEAD-box ATPase Sub2 in association with THO or Yra1

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    Ren, Yi [Laboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States; Schmiege, Philip [Laboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States; Blobel, Günter [Laboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States

    2017-01-06

    mRNA is cotranscrptionally processed and packaged into messenger ribonucleoprotein particles (mRNPs) in the nucleus. Prior to export through the nuclear pore, mRNPs undergo several obligatory remodeling reactions. In yeast, one of these reactions involves loading of the mRNA-binding protein Yra1 by the DEAD-box ATPase Sub2 as assisted by the hetero-pentameric THO complex. To obtain molecular insights into reaction mechanisms, we determined crystal structures of two relevant complexes: a THO hetero-pentamer bound to Sub2 at 6.0 Å resolution; and Sub2 associated with an ATP analogue, RNA, and a C-terminal fragment of Yra1 (Yra1-C) at 2.6 Å resolution. We found that the 25 nm long THO clamps Sub2 in a half-open configuration; in contrast, when bound to the ATP analogue, RNA and Yra1-C, Sub2 assumes a closed conformation. Both THO and Yra1-C stimulated Sub2’s intrinsic ATPase activity. We propose that THO surveys common landmarks in each nuclear mRNP to localize Sub2 for targeted loading of Yra1.

  17. Structural and biochemical analyses of the DEAD-box ATPase Sub2 in association with THO or Yra1.

    Science.gov (United States)

    Ren, Yi; Schmiege, Philip; Blobel, Günter

    2017-01-06

    mRNA is cotranscrptionally processed and packaged into messenger ribonucleoprotein particles (mRNPs) in the nucleus. Prior to export through the nuclear pore, mRNPs undergo several obligatory remodeling reactions. In yeast, one of these reactions involves loading of the mRNA-binding protein Yra1 by the DEAD-box ATPase Sub2 as assisted by the hetero-pentameric THO complex. To obtain molecular insights into reaction mechanisms, we determined crystal structures of two relevant complexes: a THO hetero-pentamer bound to Sub2 at 6.0 Å resolution; and Sub2 associated with an ATP analogue, RNA, and a C-terminal fragment of Yra1 (Yra1-C) at 2.6 Å resolution. We found that the 25 nm long THO clamps Sub2 in a half-open configuration; in contrast, when bound to the ATP analogue, RNA and Yra1-C, Sub2 assumes a closed conformation. Both THO and Yra1-C stimulated Sub2's intrinsic ATPase activity. We propose that THO surveys common landmarks in each nuclear mRNP to localize Sub2 for targeted loading of Yra1.

  18. The DEAD/DEAH box helicase, DDX11, is essential for the survival of advanced melanomas

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    Bhattacharya Chitralekha

    2012-11-01

    Full Text Available Abstract Background Despite continuous efforts to identify genes that are pivotal regulators of advanced melanoma and closely related to it, to determine which of these genes have to be blocked in their function to keep this highly aggressive disease in check, it is far from clear which molecular pathway(s and specific genes therein, is the Achilles’ heel of primary and metastatic melanoma. In this report, we present data, which document that the DEAD-box helicase DDX11, which is required for sister chromatid cohesion, is a crucial gatekeeper for melanoma cell survival. Methods Performing immunohistochemistry and immunoblot analysis, we determined expression of DDX11 in melanoma tissues and cell lines. Following transfection of melanoma cells with a DDX11-specific siRNA, we conducted a qPCR analysis to determine downregulation of DDX11 in the transfected melanoma cells. In subsequent studies, which focused upon an analysis of fluorescently labeled as well as Giesma-stained chromosome spreads, a proliferation analysis and apoptosis assays, we determined the impact of suppressing DDX11 expression on melanoma cells representing advanced melanoma. Result The findings of the study presented herein document that DDX11 is upregulated with progression from noninvasive to invasive melanoma, and that it is expressed at high levels in advanced melanoma. Furthermore, and equally important, we demonstrate that blocking the expression of DDX11 leads not only to inhibition of melanoma cell proliferation and severe defects in chromosome segregation, but also drives melanoma cells rapidly into massive apoptosis. Conclusion To date, little is known as to whether helicases play a role in melanoma development and specifically, in the progression from early to advanced melanoma. In this report, we show that the helicase DDX11 is expressed at high levels in primary and metastatic melanoma, and that interfering with its expression leads to severe chromosome

  19. Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA

    DEFF Research Database (Denmark)

    Andersen, Christian Brix Folsted; Ballut, Lionel; Johansen, Jesper Sanderhoff

    2006-01-01

    exon junction core complex containing the DEAD-box adenosine triphosphatase (ATPase) eukaryotic initiation factor 4AIII (eIF4AIII) bound to an ATP analog, MAGOH, Y14, a fragment of MLN51, and a polyuracil mRNA mimic. eIF4AIII interacts with the phosphate-ribose backbone of six consecutive nucleotides...... and prevents part of the bound RNA from being double stranded. The MAGOH and Y14 subunits lock eIF4AIII in a prehydrolysis state, and activation of the ATPase probably requires only modest conformational changes in eIF4AIII motif I....

  20. Pea p68, a DEAD-box helicase, provides salinity stress tolerance in transgenic tobacco by reducing oxidative stress and improving photosynthesis machinery.

    Directory of Open Access Journals (Sweden)

    Narendra Tuteja

    Full Text Available The DEAD-box helicases are required mostly in all aspects of RNA and DNA metabolism and they play a significant role in various abiotic stresses, including salinity. The p68 is an important member of the DEAD-box proteins family and, in animal system, it is involved in RNA metabolism including pre-RNA processing and splicing. In plant system, it has not been well characterized. Here we report the cloning and characterization of p68 from pea (Pisum sativum and its novel function in salinity stress tolerance in plant.The pea p68 protein self-interacts and is localized in the cytosol as well as the surrounding of cell nucleus. The transcript of pea p68 is upregulated in response to high salinity stress in pea. Overexpression of p68 driven by constitutive cauliflower mosaic virus-35S promoter in tobacco transgenic plants confers enhanced tolerances to salinity stress by improving the growth, photosynthesis and antioxidant machinery. Under stress treatment, pea p68 overexpressing tobacco accumulated higher K+ and lower Na+ level than the wild-type plants. Reactive oxygen species (ROS accumulation was remarkably regulated by the overexpression of pea p68 under salinity stress conditions, as shown from TBARS content, electrolyte leakage, hydrogen peroxide accumulation and 8-OHdG content and antioxidant enzyme activities.To the best of our knowledge this is the first direct report, which provides the novel function of pea p68 helicase in salinity stress tolerance. The results suggest that p68 can also be exploited for engineering abiotic stress tolerance in crop plants of economic importance.

  1. DEAD-box helicase DDX27 regulates 3′ end formation of ribosomal 47S RNA and stably associates with the PeBoW-complex

    Energy Technology Data Exchange (ETDEWEB)

    Kellner, Markus; Rohrmoser, Michaela [Department of Molecular Epigenetics, Helmholtz Center Munich, Center for Integrated Protein Science Munich (CIPSM), Marchioninistr. 25, Munich 81377 (Germany); Forné, Ignasi [Adolf Butenandt Institute, Ludwig Maximilians University of Munich, Center for Integrated Protein Science Munich (CIPSM), Schillerstr. 44, Munich 80336 (Germany); Voss, Kirsten; Burger, Kaspar; Mühl, Bastian; Gruber-Eber, Anita [Department of Molecular Epigenetics, Helmholtz Center Munich, Center for Integrated Protein Science Munich (CIPSM), Marchioninistr. 25, Munich 81377 (Germany); Kremmer, Elisabeth [Institute of Molecular Immunology, Helmholtz Center Munich, Marchioninistr. 25, Munich 81377 (Germany); Imhof, Axel [Adolf Butenandt Institute, Ludwig Maximilians University of Munich, Center for Integrated Protein Science Munich (CIPSM), Schillerstr. 44, Munich 80336 (Germany); Eick, Dirk, E-mail: eick@helmholtz-muenchen.de [Department of Molecular Epigenetics, Helmholtz Center Munich, Center for Integrated Protein Science Munich (CIPSM), Marchioninistr. 25, Munich 81377 (Germany)

    2015-05-15

    PeBoW, a trimeric complex consisting of pescadillo (Pes1), block of proliferation (Bop1), and the WD repeat protein 12 (WDR12), is essential for processing and maturation of mammalian 5.8S and 28S ribosomal RNAs. Applying a mass spectrometric analysis, we identified the DEAD-box helicase DDX27 as stably associated factor of the PeBoW-complex. DDX27 interacts with the PeBoW-complex via an evolutionary conserved F×F motif in the N-terminal domain and is recruited to the nucleolus via its basic C-terminal domain. This recruitment is RNA-dependent and occurs independently of the PeBoW-complex. Interestingly, knockdown of DDX27, but not of Pes1, induces the accumulation of an extended form of the primary 47S rRNA. We conclude that DDX27 can interact specifically with the Pes1 and Bop1 but fulfils critical function(s) for proper 3′ end formation of 47S rRNA independently of the PeBoW-complex. - Highlights: • DEAD-box helicase DDX27 is a new constituent of the PeBoW-complex. • The N-terminal F×F motif of DDX27 interacts with the PeBoW components Pes1 and Bop1. • Nucleolar anchoring of DDX27 via its basic C-terminal domain is RNA dependent. • Knockdown of DDX27 induces a specific defect in 3′ end formation of 47S rRNA.

  2. The p68 and p72 DEAD box RNA helicases interact with HDAC1 and repress transcription in a promoter-specific manner

    Science.gov (United States)

    Wilson, Brian J; Bates, Gaynor J; Nicol, Samantha M; Gregory, David J; Perkins, Neil D; Fuller-Pace, Frances V

    2004-01-01

    Background p68 (Ddx5) and p72 (Ddx17) are highly related members of the DEAD box family and are established RNA helicases. They have been implicated in growth regulation and have been shown to be involved in both pre-mRNA and pre-rRNA processing. More recently, however, these proteins have been reported to act as transcriptional co-activators for estrogen-receptor alpha (ERα). Furthermore these proteins were shown to interact with co-activators p300/CBP and the RNA polymerase II holoenzyme. Taken together these reports suggest a role for p68 and p72 in transcriptional activation. Results In this report we show that p68 and p72 can, in some contexts, act as transcriptional repressors. Targeting of p68 or p72 to constitutive promoters leads to repression of transcription; this repression is promoter-specific. Moreover both p68 and p72 associate with histone deacetylase 1 (HDAC1), a well-established transcriptional repression protein. Conclusions It is therefore clear that p68 and p72 are important transcriptional regulators, functioning as co-activators and/or co-repressors depending on the context of the promoter and the transcriptional complex in which they exist. PMID:15298701

  3. The p68 and p72 DEAD box RNA helicases interact with HDAC1 and repress transcription in a promoter-specific manner

    Directory of Open Access Journals (Sweden)

    Nicol Samantha M

    2004-08-01

    Full Text Available Abstract Background p68 (Ddx5 and p72 (Ddx17 are highly related members of the DEAD box family and are established RNA helicases. They have been implicated in growth regulation and have been shown to be involved in both pre-mRNA and pre-rRNA processing. More recently, however, these proteins have been reported to act as transcriptional co-activators for estrogen-receptor alpha (ERα. Furthermore these proteins were shown to interact with co-activators p300/CBP and the RNA polymerase II holoenzyme. Taken together these reports suggest a role for p68 and p72 in transcriptional activation. Results In this report we show that p68 and p72 can, in some contexts, act as transcriptional repressors. Targeting of p68 or p72 to constitutive promoters leads to repression of transcription; this repression is promoter-specific. Moreover both p68 and p72 associate with histone deacetylase 1 (HDAC1, a well-established transcriptional repression protein. Conclusions It is therefore clear that p68 and p72 are important transcriptional regulators, functioning as co-activators and/or co-repressors depending on the context of the promoter and the transcriptional complex in which they exist.

  4. A DEAD box RNA helicase is essential for mRNA export and important for development and stress responses in Arabidopsis.

    Science.gov (United States)

    Gong, Zhizhong; Dong, Chun-Hai; Lee, Hojoung; Zhu, Jianhua; Xiong, Liming; Gong, Deming; Stevenson, Becky; Zhu, Jian-Kang

    2005-01-01

    An Arabidopsis thaliana mutant, cryophyte, was isolated and found to have an enhanced cold stress-induction of the master regulator of cold tolerance, C-repeat binding factor 2 (CBF2), and its downstream target genes. The mutant is more tolerant to chilling and freezing stresses but is more sensitive to heat stress. Under warm but not cold growth temperatures, the mutant has a reduced stature and flowers earlier. Under long day conditions, flowering of the mutant is insensitive to vernalization. The mutant is also hypersensitive to the phytohormone abscisic acid. The mutation was found in a DEAD box RNA helicase gene that is identical to the previously identified low expression of osmotically responsive genes 4 (LOS4) locus, which was defined by the los4-1 mutation that reduces cold regulation of CBFs and their target genes and renders Arabidopsis plants chilling sensitive. We show evidence suggesting that the CRYOPHYTE/LOS4 protein may be enriched in the nuclear rim. In situ poly(A) hybridization indicates that the export of poly(A)+ RNAs is blocked in the cryophyte/los4-2 mutant at warm or high temperatures but not at low temperatures, whereas the los4-1 mutation weakens mRNA export at both low and warm temperatures. These results demonstrate an important role of the CRYOPHYTE/LOS4 RNA helicase in mRNA export, plant development, and stress responses.

  5. Multiple modes of chromatin remodeling by Forkhead box proteins.

    Science.gov (United States)

    Lalmansingh, Avin S; Karmakar, Sudipan; Jin, Yetao; Nagaich, Akhilesh K

    2012-07-01

    Forkhead box (FOX) proteins represent a large family of transcriptional regulators unified by their DNA binding domain (DBD) known as a 'forkhead' or 'winged helix' domain. Over 40 FOX genes have been identified in the mammalian genome. FOX proteins share significant sequence similarities in the DBD which allow them to bind to a consensus DNA response element. However, their modes of action are quite diverse as they regulate gene expression by acting as pioneer factors, transcription factors, or both. This review focuses on the mechanisms of chromatin remodeling with an emphasis on three sub-classes-FOXA, FOXO, and FOXP members. FOXA proteins serve as pioneer factors to open up local chromatin structure and thereby increase accessibility of chromatin to factors regulating transcription. FOXP proteins, in contrast, function as classic transcription factors to recruit a variety of chromatin modifying enzymes to regulate gene expression. FOXO proteins represent a hybrid subclass having dual roles as pioneering factors and transcription factors. A subset of FOX proteins interacts with condensed mitotic chromatin and may function as 'bookmarking' agents to maintain transcriptional competence at specific genomic sites. The overall diversity in chromatin remodeling function by FOX proteins is related to unique structural motifs present within the DBD flanking regions that govern selective interactions with core histones and/or chromatin coregulatory proteins. This article is part of a Special Issue entitled: Chromatin in time and space. Published by Elsevier B.V.

  6. Binding of DEAD-box helicase Dhh1 to the 5'-untranslated region of ASH1 mRNA represses localized translation of ASH1 in yeast cells.

    Science.gov (United States)

    Zhang, Qianjun; Meng, Xiuhua; Li, Delin; Chen, Shaoyin; Luo, Jianmin; Zhu, Linjie; Singer, Robert H; Gu, Wei

    2017-06-09

    Local translation of specific mRNAs is regulated by dynamic changes in their subcellular localization, and these changes are due to complex mechanisms controlling cytoplasmic mRNA transport. The budding yeast Saccharomyces cerevisiae is well suited to studying these mechanisms because many of its transcripts are transported from the mother cell to the budding daughter cell. Here, we investigated the translational control of ASH1 mRNA after transport and localization. We show that although ASH1 transcripts were translated after they reached the bud tip, some mRNAs were bound by the RNA-binding protein Puf6 and were non-polysomal. We also found that the DEAD-box helicase Dhh1 complexed with the untranslated ASH1 mRNA and Puf6. Loss of Dhh1 affected local translation of ASH1 mRNA and resulted in delocalization of ASH1 transcript in the bud. Forcibly shifting the non-polysomal ASH1 mRNA into polysomes was associated with Dhh1 dissociation. We further demonstrated that Dhh1 is not recruited to ASH1 mRNA co-transcriptionally, suggesting that it could bind to ASH1 mRNA within the cytoplasm. Of note, Dhh1 bound to the 5'-UTR of ASH1 mRNA and inhibited its translation in vitro These results suggest that after localization to the bud tip, a portion of the localized ASH1 mRNA becomes translationally inactive because of binding of Dhh1 and Puf6 to the 5'- and 3'-UTRs of ASH1 mRNA. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Bioactive L acidissima protein hydrolysates using Box-Behnken design.

    Science.gov (United States)

    Sonawane, Sachin K; Arya, Shalini S

    2017-07-01

    This study examines the extraction and hydrolysis of proteins using single factor and Box-Behnken Design (BBD). From single factor tests, optimised extraction parameters were 1% alkali concentration, 40 °C temperature, 60 min time, and 1:20 solid to alkali ratio. Under these conditions; 924.31 mg/g of total protein was obtained from Limonia acidissima (L acidissima). The maximum degree of hydrolysis was 39.82% at pH 2, enzyme to substrate ratio 2.5% (w/w), and hydrolysis time was 42.41 min using BBD design. L acidissima seed protein hydrolysate showed 32.94% DPPH and 88.18% of ABTS activity at concentration of 100 µg/ml and 1 mg/ml, respectively. Reducing power of 0.16 and metal chelating activity of 87.39% was obtained from 5 mg/ml protein hydrolysates. This implied that L acidissima seed protein hydrolysate could be utilised in protein rich product or as protein supplements.

  8. High Mobility Group Box Protein-1 in Wound Repair

    Directory of Open Access Journals (Sweden)

    Mauro Patrone

    2012-09-01

    Full Text Available High-mobility group box 1 protein (HMGB1, a member of highly conserved non-histone DNA binding protein family, has been studied as transcription factor and growth factor. Secreted extracellularly by activated monocytes and macrophages or passively released by necrotic or damaged cells, extracellular HMGB1 is a potent mediator of inflammation. Extracellular HMGB1 has apparently contrasting biological actions: it sustains inflammation (with the possible establishment of autoimmunity or of self-maintaining tissue damage, but it also activates and recruits stem cells, boosting tissue repair. Here, we focus on the role of HMGB1 in physiological and pathological responses, the mechanisms by which it contributes to tissue repair and therapeutic strategies base on targeting HMGB1.

  9. Classification, expression pattern, and E3 ligase activity assay of rice U-box-containing proteins.

    Science.gov (United States)

    Zeng, Li-Rong; Park, Chan Ho; Venu, R C; Gough, Julian; Wang, Guo-Liang

    2008-09-01

    Ubiquitin ligases play a central role in determining the specificity of the ubiquitination system by selecting a myriad of appropriate candidate proteins for modification. The U-box is a recently identified, ubiquitin ligase activity-related protein domain that shows greater presence in plants than in other organisms. In this study, we identified 77 putative U-box proteins from the rice genome using a battery of whole genome analysis algorithms. Most of the U-box protein genes are expressed, as supported by the identification of their corresponding expressed sequence tags (ESTs), full-length cDNAs, or massively parallel signature sequencing (MPSS) tags. Using the same algorithms, we identified 61 U-box proteins from the Arabidopsis genome. The rice and Arabidopsis U-box proteins were classified into nine major classes based on their domain compositions. Comparison between rice and Arabidopsis U-box proteins indicates that the majority of rice and Arabidopsis U-box proteins have the same domain organizations. The inferred phylogeny established the homology between rice and Arabidopsis U-box/ARM proteins. Cell death assay using the rice protoplast system suggests that one rice U-box gene, OsPUB51, might act as a negative regulator of cell death signaling. In addition, the selected U-box proteins were found to be functional E3 ubiquitin ligases. The identification and analysis of rice U-box proteins hereby at the genomic level will help functionally characterize this class of E3 ubiquitin ligase in the future.

  10. Regulating the ethylene response of a plant by modulation of F-box proteins

    Science.gov (United States)

    Guo, Hongwei [Beijing, CN; Ecker, Joseph R [Carlsbad, CA

    2014-01-07

    The relationship between F-box proteins and proteins invovled in the ethylene response in plants is described. In particular, F-box proteins may bind to proteins involved in the ethylene response and target them for degradation by the ubiquitin/proteasome pathway. The transcription factor EIN3 is a key transcription factor mediating ethylne-regulated gene expression and morphological responses. EIN3 is degraded through a ubiquitin/proteasome pathway mediated by F-box proteins EBF1 and EBF2. The link between F-box proteins and the ethylene response is a key step in modulating or regulating the response of a plant to ethylene. Described herein are transgenic plants having an altered sensitivity to ethylene, and methods for making transgenic plant haing an althered sensitivity to ethylene by modulating the level of activity of F-box proteins. Methods of altering the ethylene response in a plant by modulating the activity or expression of an F-box protein are described. Also described are methods of identifying compounds that modulate the ethylene response in plants by modulating the level of F-box protein expression or activity.

  11. Crystal structure of Methanococcus jannaschii TATA box-binding protein.

    Science.gov (United States)

    Adachi, Naruhiko; Senda, Miki; Natsume, Ryo; Senda, Toshiya; Horikoshi, Masami

    2008-11-01

    As the archaeal transcription system consists of a eukaryotic-type transcription apparatus and bacterial-type regulatory transcription factors, analyses of the molecular interface between the transcription apparatus and regulatory transcription factors are critical to reveal the evolutionary change of the transcription system. TATA box-binding protein (TBP), the central components of the transcription apparatus are classified into three groups: eukaryotic, archaeal-I and archaeal-II TBPs. Thus, comparative functional analysis of these three groups of TBP is important for the study of the evolution of the transcription system. Here, we present the first crystal structure of an archaeal-II TBP from Methanococcus jannaschii. The highly conserved and group-specific conserved surfaces of TBP bind to DNA and TFIIB/TFB, respectively. The phylogenetic trees of TBP and TFIIB/TFB revealed that they evolved in a coupled manner. The diversified surface of TBP is negatively charged in the archaeal-II TBP, which is completely different from the case of eukaryotic and archaeal-I TBPs, which are positively charged and biphasic, respectively. This difference is responsible for the diversification of the regulatory functions of TBP during evolution.

  12. Forkhead Box Protein A2 (FOXA2) Protein Stability and Activity Are Regulated by Sumoylation

    OpenAIRE

    Belaguli, Narasimhaswamy S.; Zhang, Mao; Brunicardi, F. Charles; Berger, David H.

    2012-01-01

    The forkhead box protein A2 (FOXA2) is an important regulator of glucose and lipid metabolism and organismal energy balance. Little is known about how FOXA2 protein expression and activity are regulated by post-translational modifications. We have identified that FOXA2 is post-translationally modified by covalent attachment of a small ubiquitin related modifier-1 (SUMO-1) and mapped the sumoylation site to the amino acid lysine 6 (K6). Preventing sumoylation by mutating the SUMO acceptor K6 t...

  13. Role of indirect readout mechanism in TATA box binding protein-DNA interaction

    Science.gov (United States)

    Mondal, Manas; Choudhury, Devapriya; Chakrabarti, Jaydeb; Bhattacharyya, Dhananjay

    2015-03-01

    Gene expression generally initiates from recognition of TATA-box binding protein (TBP) to the minor groove of DNA of TATA box sequence where the DNA structure is significantly different from B-DNA. We have carried out molecular dynamics simulation studies of TBP-DNA system to understand how the DNA structure alters for efficient binding. We observed rigid nature of the protein while the DNA of TATA box sequence has an inherent flexibility in terms of bending and minor groove widening. The bending analysis of the free DNA and the TBP bound DNA systems indicate presence of some similar structures. Principal coordinate ordination analysis also indicates some structural features of the protein bound and free DNA are similar. Thus we suggest that the DNA of TATA box sequence regularly oscillates between several alternate structures and the one suitable for TBP binding is induced further by the protein for proper complex formation.

  14. The F-Box Protein Fbp1 Shapes the Immunogenic Potential of Cryptococcus neoformans

    Directory of Open Access Journals (Sweden)

    Jorge Masso-Silva

    2018-01-01

    Full Text Available Cryptococcus neoformans is the main etiologic agent of cryptococcal meningitis and causes a significant number of deadly infections per year. Although it is well appreciated that host immune responses are crucial for defense against cryptococcosis, our understanding of factors that control the development of effective immunity to this fungus remains incomplete. In previous studies, we identified the F-box protein Fbp1 as a novel determinant of C. neoformans virulence. In this study, we found that the hypovirulence of the fbp1Δ mutant is linked to the development of a robust host immune response. Infection with the fbp1Δ mutant induces a rapid influx of CCR2+ monocytes and their differentiation into monocyte-derived dendritic cells (mo-DCs. Depletion of CCR2+ monocytes and their derivative mo-DCs resulted in impaired activation of a protective inflammatory response and the rapid death of mice infected with the fbp1Δ mutant. Mice lacking B and T cells also developed fungal meningitis and succumbed to infection with the fbp1Δ mutant, demonstrating that adaptive immune responses to the fbp1Δ mutant help to maintain the long-term survival of the host. Adaptive immune responses to the fbp1Δ mutant were characterized by enhanced differentiation of Th1 and Th17 CD4+ T cells together with diminished Th2 responses compared to the H99 parental strain. Importantly, we found that the enhanced immunogenicity of fbp1Δ mutant yeast cells can be harnessed to confer protection against a subsequent infection with the virulent H99 parental strain. Altogether, our findings suggest that Fbp1 functions as a novel virulence factor that shapes the immunogenicity of C. neoformans.

  15. Functional redundancy and/or ongoing pseudogenization among F-box protein genes expressed in Arabidopsis male gametophyte.

    Science.gov (United States)

    Ikram, Sobia; Durandet, Monique; Vesa, Simona; Pereira, Serge; Guerche, Philippe; Bonhomme, Sandrine

    2014-06-01

    F-box protein genes family is one of the largest gene families in plants, with almost 700 predicted genes in the model plant Arabidopsis. F-box proteins are key components of the ubiquitin proteasome system that allows targeted protein degradation. Transcriptome analyses indicate that half of these F-box protein genes are found expressed in microspore and/or pollen, i.e., during male gametogenesis. To assess the role of F-box protein genes during this crucial developmental step, we selected 34 F-box protein genes recorded as highly and specifically expressed in pollen and isolated corresponding insertion mutants. We checked the expression level of each selected gene by RT-PCR and confirmed pollen expression for 25 genes, but specific expression for only 10 of the 34 F-box protein genes. In addition, we tested the expression level of selected F-box protein genes in 24 mutant lines and showed that 11 of them were null mutants. Transmission analysis of the mutations to the progeny showed that none of the single mutations was gametophytic lethal. These unaffected transmission efficiencies suggested leaky mutations or functional redundancy among F-box protein genes. Cytological observation of the gametophytes in the mutants confirmed these results. Combinations of mutations in F-box protein genes from the same subfamily did not lead to transmission defect either, further highlighting functional redundancy and/or a high proportion of pseudogenes among these F-box protein genes.

  16. Stepwise bending of DNA by a single TATA box binding protein

    DEFF Research Database (Denmark)

    Tolic-Nørrelykke, Simon F; Rasmussen, Mette B; Pavone, Francesco S

    2006-01-01

    The TATA-box binding protein (TBP) is required by all three eucaryotic RNA polymerases for the initiation of transcription from most promoters. TBP recognizes, binds to, and bends promoter sequences called "TATA-boxes" in the DNA. We present results from the study of individual Saccharomyces...... cerevisiae TBPs interacting with single DNA molecules containing a TATA-box. Using video microscopy, we observed the Brownian motion of the beads tethered by short surface-bound DNA. When TBP binds to and bends the DNA, the conformation of the DNA changes and the amplitude of Brownian motion of the tehtered...

  17. Changing MADS-Box Transcription Factor Protein-Protein Interactions as a Mechanism for Generating Floral Morphological Diversity.

    Science.gov (United States)

    Bartlett, Madelaine E

    2017-12-01

    Flowers display fantastic morphological diversity. Despite extreme variability in form, floral organ identity is specified by a core set of deeply conserved proteins-the floral MADS-box transcription factors. This indicates that while core gene function has been maintained, MADS-box transcription factors have evolved to regulate different downstream genes. Thus, the evolution of gene regulation downstream of the MADS-box transcription factors is likely central to the evolution of floral form. Gene regulation is determined by the combination of transcriptional regulators present at a particular cis-regulatory element at a particular time. Therefore, the interactions between transcription factors can be of profound importance in determining patterns of gene regulation. Here, after a short primer on flowers and floral morphology, I discuss the centrality of protein-protein interactions to MADS-box transcription factor function, and review the evidence that the evolution of MADS-box protein-protein interactions is a key driver in the evolution of gene regulation downstream of the MADS-box genes. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  18. Classification of EA1-box proteins and new insights into their role during reproduction in grasses.

    Science.gov (United States)

    Uebler, Susanne; Márton, Mihaela L; Dresselhaus, Thomas

    2015-12-01

    EA1-box protein classification. Success in reproduction and vegetative development in flowering plants strongly depends on precise cell-to-cell signaling events mediated by secreted peptides.A small peptide family named as EA1-like (EAL) has been first described 10 years ago and includes EA1 involved in pollen tubes attraction by the female gametophyte and EAL1-regulating germ cell identity in maize. EALs consist of an N-terminal endoplasmic reticulum-targeting motif, the highly conserved EA1-box and a short C-terminal alanine-rich domain. Whereas EAL peptides are exclusively found in the Gramineae, the EA1-box is widely distributed throughout the plant kingdom. Based on in silico analysis and subcellular localization studies, we report here a new classification of EA1-box proteins in flowering plants. They can be distinguished into three protein classes: the already defined EAL proteins, the EAG (EA1-box glycine-rich) proteins and the EAC (EA1-box containing)proteins. While fusion proteins of EAL and EAC classes locate to the secretory pathway, EAGs are cytoplasmic and locate also to the nucleus. Moreover, we further show that the third EAL protein of Zea mays, EAL2, appears to be also involved in processes related to late embryogenic development as its peptide level increases after formation of leaf primordia. Immunohistochemical studies indicate its presence in the scutellar parenchyma and around the vasculature, where it is secreted to the extracellular space. In conclusion, the members of the maize EAL family possess very diverse functions during reproduction and it will now be exciting to elucidate the functions of EAGs and EACs in plants.

  19. Forkhead box protein A2 (FOXA2 protein stability and activity are regulated by sumoylation.

    Directory of Open Access Journals (Sweden)

    Narasimhaswamy S Belaguli

    Full Text Available The forkhead box protein A2 (FOXA2 is an important regulator of glucose and lipid metabolism and organismal energy balance. Little is known about how FOXA2 protein expression and activity are regulated by post-translational modifications. We have identified that FOXA2 is post-translationally modified by covalent attachment of a small ubiquitin related modifier-1 (SUMO-1 and mapped the sumoylation site to the amino acid lysine 6 (K6. Preventing sumoylation by mutating the SUMO acceptor K6 to arginine resulted in downregulation of FOXA2 protein but not RNA expression in INS-1E insulinoma cells. K6R mutation also downregulated FOXA2 protein levels in HepG2 hepatocellular carcinoma cells, HCT116 colon cancer cells and LNCaP and DU145 prostate cancer cells. Further, interfering with FOXA2 sumoylation through siRNA mediated knockdown of UBC9, an essential SUMO E2 conjugase, resulted in downregulation of FOXA2 protein levels. Stability of sumoylation deficient FOXA2K6R mutant protein was restored when SUMO-1 was fused in-frame. FOXA2 sumoylation and FOXA2 protein levels were increased by PIAS1 SUMO ligase but not a SUMO ligase activity deficient PIAS1 mutant. Although expressed at lower levels, sumoylation deficient FOXA2K6R mutant protein was detectable in the nucleus indicating that FOXA2 nuclear localization is independent of sumoylation. Sumoylation increased the transcriptional activity of FOXA2 on Pdx-1 area I enhancer. Together, our results show that sumoylation regulates FOXA2 protein expression and activity.

  20. Forkhead box protein A2 (FOXA2) protein stability and activity are regulated by sumoylation.

    Science.gov (United States)

    Belaguli, Narasimhaswamy S; Zhang, Mao; Brunicardi, F Charles; Berger, David H

    2012-01-01

    The forkhead box protein A2 (FOXA2) is an important regulator of glucose and lipid metabolism and organismal energy balance. Little is known about how FOXA2 protein expression and activity are regulated by post-translational modifications. We have identified that FOXA2 is post-translationally modified by covalent attachment of a small ubiquitin related modifier-1 (SUMO-1) and mapped the sumoylation site to the amino acid lysine 6 (K6). Preventing sumoylation by mutating the SUMO acceptor K6 to arginine resulted in downregulation of FOXA2 protein but not RNA expression in INS-1E insulinoma cells. K6R mutation also downregulated FOXA2 protein levels in HepG2 hepatocellular carcinoma cells, HCT116 colon cancer cells and LNCaP and DU145 prostate cancer cells. Further, interfering with FOXA2 sumoylation through siRNA mediated knockdown of UBC9, an essential SUMO E2 conjugase, resulted in downregulation of FOXA2 protein levels. Stability of sumoylation deficient FOXA2K6R mutant protein was restored when SUMO-1 was fused in-frame. FOXA2 sumoylation and FOXA2 protein levels were increased by PIAS1 SUMO ligase but not a SUMO ligase activity deficient PIAS1 mutant. Although expressed at lower levels, sumoylation deficient FOXA2K6R mutant protein was detectable in the nucleus indicating that FOXA2 nuclear localization is independent of sumoylation. Sumoylation increased the transcriptional activity of FOXA2 on Pdx-1 area I enhancer. Together, our results show that sumoylation regulates FOXA2 protein expression and activity.

  1. Conserved features of complexes of TATA-box binding proteins with DNA.

    Science.gov (United States)

    Zanegina, Olga; Aksianov, Evgeniy; Alexeevski, Andrei V; Karyagina, Anna; Spirin, Sergei

    2016-04-01

    A comparative analysis of all available structures of complexes of TATA-box binding proteins (TBPs) with DNA is performed. Conserved features of DNA-protein interaction are described, including nine amino acid residues that form conserved hydrogen bonds, 13 residues participating in formation of two conserved hydrophobic clusters at DNA-protein interface, and four conserved water-mediated contacts. Partial symmetry of conserved contacts reflects quasi-symmetry of TBP structure.

  2. The Me31B DEAD-box helicase localizes to postsynaptic foci and regulates expression of a CaMKII reporter mRNA in dendrites of Drosophila olfactory projection neurons

    Directory of Open Access Journals (Sweden)

    Jens Hillebrand

    2010-11-01

    Full Text Available mRNP granules at adult central synapses are postulated to regulate local mRNA translation and synapse plasticity. However, they are very poorly characterized in vivo. Here, in Drosophila olfactory synapses, we present early observations and characterization of candidate synaptic mRNP particles, one of which contains a widely conserved, DEAD-box helicase, Me31B. In Drosophila, Me31B is required for translational repression of maternal and miRNA-target mRNAs. A role in neuronal translational control is primarily suggested by Me31B’s localization, in cultured primary neurons, to neuritic mRNP granules that contain: i various translational regulators; ii CaMKII mRNA; and iii several P-body markers including the mRNA hydrolases, Dcp1 and Pcm/Xrn-1. In adult neurons, Me31B localizes to P-body like cytoplasmic foci/particles in neuronal soma. In addition it is present to synaptic foci that may lack RNA degradative enzymes and localize predominantly to dendritic elements of olfactory sensory and projection neurons. MARCM clones of projection-neurons mutant for Me31B show loss of both Me31B and Dcp1-positive dendritic puncta, suggesting potential interactions between these granule types. In projection neurons, expression of validated hairpin-RNAi constructs against Me31B causes visible knockdown of endogenous protein, as assessed by the brightness and number of Me31B puncta. Knockdown of Me31B also causes a substantial elevation in observed levels of a translational reporter of CaMKII, a postsynaptic protein whose mRNA has been shown to be localized to projection neuron dendrites and to be translationally regulated, at least in part through the miRNA pathway. Thus, neuronal Me31B is present in dendritic particles in vivo and is required for repression of a translationally regulated synaptic mRNA.

  3. The Vertebrate Protein Dead End Maintains Primordial Germ Cell Fate by Inhibiting Somatic Differentiation.

    Science.gov (United States)

    Gross-Thebing, Theresa; Yigit, Sargon; Pfeiffer, Jana; Reichman-Fried, Michal; Bandemer, Jan; Ruckert, Christian; Rathmer, Christin; Goudarzi, Mehdi; Stehling, Martin; Tarbashevich, Katsiaryna; Seggewiss, Jochen; Raz, Erez

    2017-12-18

    Maintaining cell fate relies on robust mechanisms that prevent the differentiation of specified cells into other cell types. This is especially critical during embryogenesis, when extensive cell proliferation, patterning, and migration events take place. Here we show that vertebrate primordial germ cells (PGCs) are protected from reprogramming into other cell types by the RNA-binding protein Dead end (Dnd). PGCs knocked down for Dnd lose their characteristic morphology and adopt various somatic cell fates. Concomitantly, they gain a gene expression profile reflecting differentiation into cells of different germ layers, in a process that we could direct by expression of specific cell-fate determinants. Importantly, we visualized these events within live zebrafish embryos, which provide temporal information regarding cell reprogramming. Our results shed light on the mechanisms controlling germ cell fate maintenance and are relevant for the formation of teratoma, a tumor class composed of cells from more than one germ layer. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Cyclin B1 Destruction Box-Mediated Protein Instability: The Enhanced Sensitivity of Fluorescent-Protein-Based Reporter Gene System

    Directory of Open Access Journals (Sweden)

    Chao-Hsun Yang

    2013-01-01

    Full Text Available The periodic expression and destruction of several cyclins are the most important steps for the exact regulation of cell cycle. Cyclins are degraded by the ubiquitin-proteasome system during cell cycle. Besides, a short sequence near the N-terminal of cyclin B called the destruction box (D-box; CDB is also required. Fluorescent-protein-based reporter gene system is insensitive to analysis because of the overly stable fluorescent proteins. Therefore, in this study, we use human CDB fused with both enhanced green fluorescent protein (EGFP at C-terminus and red fluorescent protein (RFP, DsRed at N-terminus in the transfected human melanoma cells to examine the effects of CDB on different fluorescent proteins. Our results indicated that CDB-fused fluorescent protein can be used to examine the slight gene regulations in the reporter gene system and have the potential to be the system for screening of functional compounds in the future.

  5. Effects of Quercetin Supplementation on Lipid and Protein Metabolism after Classic Boxing Training

    Science.gov (United States)

    Demirci, Nevzat

    2017-01-01

    The metabolic fitness (MF) is a component of athletes' physical conditioning. This study aims to investigate the effects of quercetin supplementation on Turkish Junior athletes' lipid and protein metabolism relating to MF after one month classic boxing training. Totally 20 voluntary junior male athletes were separated into two equal groups as the…

  6. Biochemical function of typical and variant Arabidopsis thaliana U-box E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Wiborg, Jakob; O'Shea, Charlotte; Skriver, Karen

    2008-01-01

    respectively, but no productive interaction was observed with the UBC15 E2 tested. The activity of AtPUB54 [Arabidopsis thaliana (thale cress) plant U-box 54 protein] was dependent on Trp(266) in the E2-binding cleft, and the E2 selectivity was changed by substitution of this position. The function...... of the distant U-box protein, AtPUB49, representing a large family of eukaryotic proteins containing a U-box linked to a cyclophilin-like peptidyl-prolyl cis-trans isomerase domain, was characterized biochemically. AtPUB49 functioned both as a prolyl isomerase and a chaperone by catalysing cis.......g. co-existence or interactions with additional domains. The biochemical functions of AtPUB49 suggest that the protein can be involved in folding or degradation of protein substrates. Similar functions can also be retained within a protein complex with separate chaperone and U-box proteins....

  7. The F-box protein FBXO44 mediates BRCA1 ubiquitination and degradation.

    Science.gov (United States)

    Lu, Yunzhe; Li, Jiezhi; Cheng, Dongmei; Parameswaran, Balaji; Zhang, Shaohua; Jiang, Zefei; Yew, P Renee; Peng, Junmin; Ye, Qinong; Hu, Yanfen

    2012-11-30

    BRCA1 mutations account for a significant proportion of familial breast and ovarian cancers. In addition, reduced BRCA1 protein is associated with sporadic cancer cases in these tissues. At the cellular level, BRCA1 plays a critical role in multiple cellular functions such as DNA repair and cell cycle checkpoint control. Its protein level is regulated in a cell cycle-dependent manner. However, regulation of BRCA1 protein stability is not fully understood. Our earlier study showed that the amino terminus of BRCA1 harbors a degron sequence that is sufficient and necessary for conferring BRCA1 degradation. In the current study, we used mass spectrometry to identify Skp1 that regulates BRCA1 protein stability. Small interfering RNA screening that targets all human F-box proteins uncovered FBXO44 as an important protein that influences BRCA1 protein level. The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro. Furthermore, the N terminus of BRCA1 mediates the interaction between BRCA1 and FBXO44. Overexpression of SCF(FBXO44) reduces BRCA1 protein level. Taken together, our work strongly suggests that SCF(FBXO44) is an E3 ubiquitin ligase responsible for BRCA1 degradation. In addition, FBXO44 expression pattern in breast carcinomas suggests that SCF(FBXO44)-mediated BRCA1 degradation might contribute to sporadic breast tumor development.

  8. The F-box Protein FBXO44 Mediates BRCA1 Ubiquitination and Degradation*

    Science.gov (United States)

    Lu, Yunzhe; Li, Jiezhi; Cheng, Dongmei; Parameswaran, Balaji; Zhang, Shaohua; Jiang, Zefei; Yew, P. Renee; Peng, Junmin; Ye, Qinong; Hu, Yanfen

    2012-01-01

    BRCA1 mutations account for a significant proportion of familial breast and ovarian cancers. In addition, reduced BRCA1 protein is associated with sporadic cancer cases in these tissues. At the cellular level, BRCA1 plays a critical role in multiple cellular functions such as DNA repair and cell cycle checkpoint control. Its protein level is regulated in a cell cycle-dependent manner. However, regulation of BRCA1 protein stability is not fully understood. Our earlier study showed that the amino terminus of BRCA1 harbors a degron sequence that is sufficient and necessary for conferring BRCA1 degradation. In the current study, we used mass spectrometry to identify Skp1 that regulates BRCA1 protein stability. Small interfering RNA screening that targets all human F-box proteins uncovered FBXO44 as an important protein that influences BRCA1 protein level. The Skp1-Cul1-F-box-protein44 (SCFFBXO44) complex ubiquitinates full-length BRCA1 in vitro. Furthermore, the N terminus of BRCA1 mediates the interaction between BRCA1 and FBXO44. Overexpression of SCFFBXO44 reduces BRCA1 protein level. Taken together, our work strongly suggests that SCFFBXO44 is an E3 ubiquitin ligase responsible for BRCA1 degradation. In addition, FBXO44 expression pattern in breast carcinomas suggests that SCFFBXO44-mediated BRCA1 degradation might contribute to sporadic breast tumor development. PMID:23086937

  9. Structural Analysis of the G-Box Domain of the Microcephaly Protein CPAP Suggests a Role in Centriole Architecture

    Science.gov (United States)

    Hatzopoulos, Georgios N.; Erat, Michèle C.; Cutts, Erin; Rogala, Kacper B.; Slater, Leanne M.; Stansfeld, Philip J.; Vakonakis, Ioannis

    2013-01-01

    Summary Centrioles are evolutionarily conserved eukaryotic organelles composed of a protein scaffold surrounded by sets of microtubules organized with a 9-fold radial symmetry. CPAP, a centriolar protein essential for microtubule recruitment, features a C-terminal domain of unknown structure, the G-box. A missense mutation in the G-box reduces affinity for the centriolar shuttling protein STIL and causes primary microcephaly. Here, we characterize the molecular architecture of CPAP and determine the G-box structure alone and in complex with a STIL fragment. The G-box comprises a single elongated β sheet capable of forming supramolecular assemblies. Structural and biophysical studies highlight the conserved nature of the CPAP-STIL complex. We propose that CPAP acts as a horizontal “strut” that joins the centriolar scaffold with microtubules, whereas G-box domains form perpendicular connections. PMID:24076405

  10. Epididymosomes transfer epididymal sperm binding protein 1 (ELSPBP1) to dead spermatozoa during epididymal transit in bovine.

    Science.gov (United States)

    D'Amours, Olivier; Frenette, Gilles; Bordeleau, Louis-Jean; Allard, Nancy; Leclerc, Pierre; Blondin, Patrick; Sullivan, Robert

    2012-10-01

    Previously, we showed that epididymal sperm binding protein 1 (ELSPBP1) characterizes spermatozoa already dead before ejaculation in bovine. In this study, we investigated the presence of ELSPBP1 in bull genital tract as well as its acquisition by spermatozoa during epididymal transit. As assessed by real-time RT-PCR, ELSPBP1 was highly expressed in the caput and the corpus epididymis but was present in lower expression levels in the testis and the cauda epididymis. Immunohistochemistry revealed the same expression pattern. However, Western blot on tissue homogenates showed some discrepancies, as ELSPBP1 was found in a comparable concentration all along the epididymis. This difference was due to the presence of ELSPBP1 in the epididymal fluid. In both caput and cauda epididymal fluid, ELSPBP1 was associated with the epididymosomes, small membranous vesicles secreted by epithelial cells of the epididymis and implicated in the transfer of proteins to spermatozoa. As assessed by immunocytometry, ELSPBP1 was found on a subset of dead spermatozoa in caput epididymis but was found on all dead spermatozoa in cauda epididymis. To assess ELSPBP1 acquisition by spermatozoa, caput epididymal spermatozoa were incubated with cauda epididymosomes under various conditions. ELSPBP1 detection by immunocytometry assay revealed that only spermatozoa already dead before incubation were receptive to ELSPBP1 transfer by epididymosomes. This receptivity was enhanced by the presence of zinc in the incubation medium. This specificity for a sperm subpopulation suggests that an underlying mechanism is involved and that ELSPBP1 could be a tag for the recognition of dead spermatozoa during epididymal transit.

  11. Roles of F-box proteins in human digestive system tumors (Review).

    Science.gov (United States)

    Gong, Jian; Lv, Liang; Huo, Jirong

    2014-12-01

    F-box proteins (FBPs), the substrate-recognition subunit of E3 ubiquitin (Ub) ligase, are the important components of Ub proteasome system (UPS). FBPs are involved in multiple cellular processes through ubiquitylation and subsequent degradation of their target proteins. Many studies have described the roles of FBPs in human cancers. Digestive system tumors account for a large proportion of all the tumors, and their mortality is very high. This review summarizes for the first time the roles of FBPs in digestive system tumorige-nesis and tumor progression, aiming at finding new routes for the rational design of targeted anticancer therapies in digestive system tumors.

  12. The TATA box regulates TATA-binding protein (TBP) dynamics in vivo.

    Science.gov (United States)

    Tora, Laszlo; Timmers, H Th Marc

    2010-06-01

    Early work established the TATA box as the predominant DNA element of core promoters which directed accurate transcription initiation by RNA polymerase II. This element is recognized by TATA-binding protein (TBP), the central DNA-binding subunit of TFIID. In vitro binding and structural experiments indicate that TBP has a strong preference for TATA and induces severe DNA bending. Recent in vivo studies in Saccharomyces cerevisiae indicate that TBP turnover is higher at TATA-containing than at TATA-less promoters; this turnover seems to be regulated by NC2 and Mot1p. We propose that bending of TATA by TBP acts in synergy with NC2 and Mot1p to release TBP more rapidly from TATA promoters in vivo, thus providing a rationale for the predominance of TATA boxes in highly regulated promoters versus constitutively active TATA-less promoters. Copyright 2010 Elsevier Ltd. All rights reserved.

  13. Development of a system for the study of protein-protein interactions in planta: characterization of a TATA-box binding protein complex in Oryza sativa.

    Science.gov (United States)

    Zhong, Jingping; Haynes, Paul A; Zhang, Shiping; Yang, Xinping; Andon, Nancy L; Eckert, Donna; Yates, John R; Wang, Xun; Budworth, Paul

    2003-01-01

    We describe a simple, rapid method for protein complex purification in planta. Using a biotin peptide as an affinity tag with TATA-box binding protein (TBP), 86 unique proteins present in the purified complex were identified by tandem mass spectrometry. We identified proteins known to be associated with TBP, and many other proteins involved in pre-mRNA processing and chromatin remodeling. The identification of these novel protein-protein associations will upon further investigations provide new insights into the mechanisms of mRNA transcription and pre-mRNA processing.

  14. A soybean MADS-box protein modulates floral organ numbers, petal identity and sterility.

    Science.gov (United States)

    Huang, Fang; Xu, Guangli; Chi, Yingjun; Liu, Haicui; Xue, Qian; Zhao, Tuanjie; Gai, Junyi; Yu, Deyue

    2014-04-02

    The MADS-box transcription factors play fundamental roles in reproductive developmental control. Although the roles of many plant MADS-box proteins have been extensively studied, there are almost no functional studies of them in soybean, an important protein and oil crop in the world. In addition, the MADS-box protein orthologs may have species-specific functions. Controlling male fertility is an important goal in plant hybrid breeding but is difficult in some crops like soybean. The morphological structure of soybean flowers prevents the cross-pollination. Understanding the molecular mechanisms for floral development will aid in engineering new sterile materials that could be applied in hybrid breeding programs in soybean. Through microarray analysis, a flower-enriched gene in soybean was selected and designated as GmMADS28. GmMADS28 belongs to AGL9/SEP subfamily of MADS-box proteins, localized in nucleus and showed specific expression patterns in floral meristems as well as stamen and petal primordia. Expression of GmMADS28 in the stamens and petals of a soybean mutant NJS-10Hfs whose stamens are converted into petals was higher than in those of wild-type plants. Constitutive expression of GmMADS28 in tobacco promoted early flowering and converted stamens and sepals to petals. Interestingly, transgenic plants increased the numbers of sepal, petal and stamen from five to six and exhibited male sterility due to the shortened and curly filaments and the failure of pollen release from the anthers. The ectopic expression of GmMADS28 was found to be sufficient to activate expression of tobacco homologs of SOC1, LEAFY, AGL8/FUL, and DEF. In addition, we observed the interactions of GmMADS28 with soybean homologs of SOC1, AP1, and AGL8/FUL proteins. In this study, we observed the roles of GmMADS28 in the regulation of floral organ number and petal identity. Compared to other plant AGL9/SEP proteins, GmMADS28 specifically regulates floral organ number, filament length and

  15. Nopaline-type Ti plasmid of Agrobacterium encodes a VirF-like functional F-box protein.

    Science.gov (United States)

    Lacroix, Benoît; Citovsky, Vitaly

    2015-11-20

    During Agrobacterium-mediated genetic transformation of plants, several bacterial virulence (Vir) proteins are translocated into the host cell to facilitate infection. One of the most important of such translocated factors is VirF, an F-box protein produced by octopine strains of Agrobacterium, which presumably facilitates proteasomal uncoating of the invading T-DNA from its associated proteins. The presence of VirF also is thought to be involved in differences in host specificity between octopine and nopaline strains of Agrobacterium, with the current dogma being that no functional VirF is encoded by nopaline strains. Here, we show that a protein with homology to octopine VirF is encoded by the Ti plasmid of the nopaline C58 strain of Agrobacterium. This protein, C58VirF, possesses the hallmarks of functional F-box proteins: it contains an active F-box domain and specifically interacts, via its F-box domain, with SKP1-like (ASK) protein components of the plant ubiquitin/proteasome system. Thus, our data suggest that nopaline strains of Agrobacterium have evolved to encode a functional F-box protein VirF.

  16. The F-box protein MAX2 functions as a positive regulator of photomorphogenesis in Arabidopsis.

    Science.gov (United States)

    Shen, Hui; Luong, Phi; Huq, Enamul

    2007-12-01

    Light is vital for plant growth and development. To respond to ambient light signals, plants are equipped with an array of photoreceptors, including phytochromes that sense red (R)/far-R (FR) regions and cryptochromes and phototropins that respond to the ultraviolet-A/blue (B) region of the light spectrum, respectively. Several positively and negatively acting components in light-signaling pathways have been identified using genetic approaches; however, the pathways are not saturated. Here, we characterize a new mutant named pleiotropic photosignaling (pps), isolated from a genetic screen under continuous R light. pps has longer hypocotyls and slightly smaller cotyledons under continuous R, FR, and B light compared to that of the wild type. pps is also hyposensitive to both R and FR light-induced seed germination. Although photosynthetic marker genes are constitutively expressed in pps in the dark at high levels, the expression of early light-regulated genes is reduced in the pps seedlings compared to wild-type seedlings under R light. PPS encodes MAX2/ORE9 (for MORE AXILLARY BRANCHES2/ORESARA9), an F-box protein involved in inflorescence architecture and senescence. MAX2 is expressed ubiquitously in the seedling stage. However, its expression is restricted to vascular tissues and meristems at adult stages. MAX2 is also localized to the nucleus. As an F-box protein, MAX2 is predicted to be a component of the SCF (for SKP, Cullin, and F-box protein) complex involved in regulated proteolysis. These results suggest that SCF(MAX2) plays critical roles in R, FR, and B light-signaling pathways. In addition, MAX2 might regulate multiple targets at different developmental stages to optimize plant growth and development.

  17. Characterization of an AGAMOUS-like MADS box protein, a probable constituent of flowering and fruit ripening regulatory system in banana.

    Directory of Open Access Journals (Sweden)

    Swarup Roy Choudhury

    Full Text Available The MADS-box family of genes has been shown to play a significant role in the development of reproductive organs, including dry and fleshy fruits. In this study, the molecular properties of an AGAMOUS like MADS box transcription factor in banana cultivar Giant governor (Musa sp, AAA group, subgroup Cavendish has been elucidated. We have detected a CArG-box sequence binding AGAMOUS MADS-box protein in banana flower and fruit nuclear extracts in DNA-protein interaction assays. The protein fraction in the DNA-protein complex was analyzed by mass spectrometry and using this information we have obtained the full length cDNA of the corresponding protein. The deduced protein sequence showed ~95% amino acid sequence homology with MA-MADS5, a MADS-box protein described previously from banana. We have characterized the domains of the identified AGAMOUS MADS-box protein involved in DNA binding and homodimer formation in vitro using full-length and truncated versions of affinity purified recombinant proteins. Furthermore, in order to gain insight about how DNA bending is achieved by this MADS-box factor, we performed circular permutation and phasing analysis using the wild type recombinant protein. The AGAMOUS MADS-box protein identified in this study has been found to predominantly accumulate in the climacteric fruit pulp and also in female flower ovary. In vivo and in vitro assays have revealed specific binding of the identified AGAMOUS MADS-box protein to CArG-box sequence in the promoters of major ripening genes in banana fruit. Overall, the expression patterns of this MADS-box protein in banana female flower ovary and during various phases of fruit ripening along with the interaction of the protein to the CArG-box sequence in the promoters of major ripening genes lead to interesting assumption about the possible involvement of this AGAMOUS MADS-box factor in banana fruit ripening and floral reproductive organ development.

  18. Characterization of an AGAMOUS-like MADS box protein, a probable constituent of flowering and fruit ripening regulatory system in banana.

    Science.gov (United States)

    Roy Choudhury, Swarup; Roy, Sujit; Nag, Anish; Singh, Sanjay Kumar; Sengupta, Dibyendu N

    2012-01-01

    The MADS-box family of genes has been shown to play a significant role in the development of reproductive organs, including dry and fleshy fruits. In this study, the molecular properties of an AGAMOUS like MADS box transcription factor in banana cultivar Giant governor (Musa sp, AAA group, subgroup Cavendish) has been elucidated. We have detected a CArG-box sequence binding AGAMOUS MADS-box protein in banana flower and fruit nuclear extracts in DNA-protein interaction assays. The protein fraction in the DNA-protein complex was analyzed by mass spectrometry and using this information we have obtained the full length cDNA of the corresponding protein. The deduced protein sequence showed ~95% amino acid sequence homology with MA-MADS5, a MADS-box protein described previously from banana. We have characterized the domains of the identified AGAMOUS MADS-box protein involved in DNA binding and homodimer formation in vitro using full-length and truncated versions of affinity purified recombinant proteins. Furthermore, in order to gain insight about how DNA bending is achieved by this MADS-box factor, we performed circular permutation and phasing analysis using the wild type recombinant protein. The AGAMOUS MADS-box protein identified in this study has been found to predominantly accumulate in the climacteric fruit pulp and also in female flower ovary. In vivo and in vitro assays have revealed specific binding of the identified AGAMOUS MADS-box protein to CArG-box sequence in the promoters of major ripening genes in banana fruit. Overall, the expression patterns of this MADS-box protein in banana female flower ovary and during various phases of fruit ripening along with the interaction of the protein to the CArG-box sequence in the promoters of major ripening genes lead to interesting assumption about the possible involvement of this AGAMOUS MADS-box factor in banana fruit ripening and floral reproductive organ development.

  19. Characterization of an AGAMOUS-like MADS Box Protein, a Probable Constituent of Flowering and Fruit Ripening Regulatory System in Banana

    Science.gov (United States)

    Roy Choudhury, Swarup; Roy, Sujit; Nag, Anish; Singh, Sanjay Kumar; Sengupta, Dibyendu N.

    2012-01-01

    The MADS-box family of genes has been shown to play a significant role in the development of reproductive organs, including dry and fleshy fruits. In this study, the molecular properties of an AGAMOUS like MADS box transcription factor in banana cultivar Giant governor (Musa sp, AAA group, subgroup Cavendish) has been elucidated. We have detected a CArG-box sequence binding AGAMOUS MADS-box protein in banana flower and fruit nuclear extracts in DNA-protein interaction assays. The protein fraction in the DNA-protein complex was analyzed by mass spectrometry and using this information we have obtained the full length cDNA of the corresponding protein. The deduced protein sequence showed ∼95% amino acid sequence homology with MA-MADS5, a MADS-box protein described previously from banana. We have characterized the domains of the identified AGAMOUS MADS-box protein involved in DNA binding and homodimer formation in vitro using full-length and truncated versions of affinity purified recombinant proteins. Furthermore, in order to gain insight about how DNA bending is achieved by this MADS-box factor, we performed circular permutation and phasing analysis using the wild type recombinant protein. The AGAMOUS MADS-box protein identified in this study has been found to predominantly accumulate in the climacteric fruit pulp and also in female flower ovary. In vivo and in vitro assays have revealed specific binding of the identified AGAMOUS MADS-box protein to CArG-box sequence in the promoters of major ripening genes in banana fruit. Overall, the expression patterns of this MADS-box protein in banana female flower ovary and during various phases of fruit ripening along with the interaction of the protein to the CArG-box sequence in the promoters of major ripening genes lead to interesting assumption about the possible involvement of this AGAMOUS MADS-box factor in banana fruit ripening and floral reproductive organ development. PMID:22984496

  20. An experimental verification of the predicted effects of promoter TATA-box polymorphisms associated with human diseases on interactions between the TATA boxes and TATA-binding protein.

    Science.gov (United States)

    Savinkova, Ludmila; Drachkova, Irina; Arshinova, Tatyana; Ponomarenko, Petr; Ponomarenko, Mikhail; Kolchanov, Nikolay

    2013-01-01

    Human genome sequencing has resulted in a great body of data, including a stunningly large number of single nucleotide polymorphisms (SNPs) with unknown phenotypic manifestations. Identification and comprehensive analysis of regulatory SNPs in human gene promoters will help quantify the effects of these SNPs on human health. Based on our experimental and computer-aided study of SNPs in TATA boxes and the use of literature data, we have derived an equation for TBP/TATA equilibrium binding in three successive steps: TATA-binding protein (TBP) sliding along DNA due to their nonspecific affinity for each other ↔ recognition of the TATA box ↔ stabilization of the TBP/TATA complex. Using this equation, we have analyzed TATA boxes containing SNPs associated with human diseases and made in silico predictions of changes in TBP/TATA affinity. An electrophoretic mobility shift assay (EMSA)-based experimental study performed under the most standardized conditions demonstrates that the experimentally measured values are highly correlated with the predicted values: the coefficient of linear correlation, r, was 0.822 at a significance level of αTATA boxes (δ= -ln[K(D,TATAMut)]-(-ln[K(D,TATAMut)])). It has been demonstrated that the SNPs associated with increased risk of human diseases such as α-, β- and δ-thalassemia, myocardial infarction and thrombophlebitis, changes in immune response, amyotrophic lateral sclerosis, lung cancer and hemophilia B Leyden cause 2-4-fold changes in TBP/TATA affinity in most cases. The results obtained strongly suggest that the TBP/TATA equilibrium binding equation derived can be used for analysis of TATA-box sequences and identification of SNPs with a potential of being functionally important.

  1. A Nitrilase-Like Protein Interacts with GCC Box DNA-Binding Proteins Involved in Ethylene and Defense Responses1

    Science.gov (United States)

    Xu, Ping; Narasimhan, Meena L.; Samson, Teresa; Coca, Maria A.; Huh, Gyung-Hye; Zhou, Jianmin; Martin, Gregory B.; Hasegawa, Paul M.; Bressan, Ray A.

    1998-01-01

    Ethylene-responsive element-binding proteins (EREBPs) of tobacco (Nicotiana tabacum L.) bind to the GCC box of many pathogenesis-related (PR) gene promoters, including osmotin (PR-5). The two GCC boxes on the osmotin promoter are known to be required, but not sufficient, for maximal ethylene responsiveness. EREBPs participate in the signal transduction pathway leading from exogenous ethylene application and pathogen infection to PR gene induction. In this study EREBP3 was used as bait in a yeast two-hybrid interaction trap with a tobacco cDNA library as prey to isolate signal transduction pathway intermediates that interact with EREBPs. One of the strongest interactors was found to encode a nitrilase-like protein (NLP). Nitrilase is an enzyme involved in auxin biosynthesis. NLP interacted with other EREBP family members, namely tobacco EREBP2 and tomato (Lycopersicon esculentum L.) Pti4/5/6. The EREBP2-EREBP3 interaction with NLP required part of the DNA-binding domain. The specificity of interaction was further confirmed by protein-binding studies in solution. We propose that the EREBP-NLP interaction serves to regulate PR gene expression by sequestration of EREBPs in the cytoplasm. PMID:9808731

  2. Guideline for making application dossiers for novel proteins; Novel food dossiers: from black box to tool box

    NARCIS (Netherlands)

    Wagenberg, van C.P.A.; Janssens, B.; Kalk, C.; Sluis, van der A.; Noordam, M.Y.; Spiegel, van der M.

    2014-01-01

    This document describes when a new protein intended to market for human consumption is considered to be a novel food protein (novel protein) and when it is not, when an application dossier for authorisation must be made and when, in general, an application dossier for notification might be

  3. TBP-like protein (TLP) interferes with Taspase1-mediated processing of TFIIA and represses TATA box gene expression.

    Science.gov (United States)

    Suzuki, Hidefumi; Isogai, Momoko; Maeda, Ryo; Ura, Kiyoe; Tamura, Taka-Aki

    2015-07-27

    TBP-TFIIA interaction is involved in the potentiation of TATA box-driven promoters. TFIIA activates transcription through stabilization of TATA box-bound TBP. The precursor of TFIIA is subjected to Taspase1-directed processing to generate α and β subunits. Although this processing has been assumed to be required for the promoter activation function of TFIIA, little is known about how the processing is regulated. In this study, we found that TBP-like protein (TLP), which has the highest affinity to TFIIA among known proteins, affects Taspase1-driven processing of TFIIA. TLP interfered with TFIIA processing in vivo and in vitro, and direct binding of TLP to TFIIA was essential for inhibition of the processing. We also showed that TATA box promoters are specifically potentiated by processed TFIIA. Processed TFIIA, but not unprocessed TFIIA, associated with the TATA box. In a TLP-knocked-down condition, not only the amounts of TATA box-bound TFIIA but also those of chromatin-bound TBP were significantly increased, resulting in the stimulation of TATA box-mediated gene expression. Consequently, we suggest that TLP works as a negative regulator of the TFIIA processing and represses TFIIA-governed and TATA-dependent gene expression through preventing TFIIA maturation. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Anabolic Properties of High Mobility Group Box Protein-1 in Human Periodontal Ligament Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Michael Wolf

    2014-01-01

    Full Text Available High mobility group box protein-1 (HMGB1 is mainly recognized as a chemoattractant for macrophages in the initial phase of host response to pathogenic stimuli. However, recent findings provide evidence for anabolic properties in terms of enhanced proliferation, migration, and support of wound healing capacity of mesenchymal cells suggesting a dual role of the cytokine in the regulation of immune response and subsequent regenerative processes. Here, we examined potential anabolic effects of HMGB1 on human periodontal ligament (PDL cells in the regulation of periodontal remodelling, for example, during orthodontic tooth movement. Preconfluent human PDL cells (hPDL were exposed to HMGB1 protein and the influence on proliferation, migration, osteogenic differentiation, and biomineralization was determined by MTS assay, real time PCR, immunofluorescence cytochemistry, ELISA, and von Kossa staining. HMGB1 protein increased hPDL cell proliferation, migration, osteoblastic marker gene expression, and protein production as well as mineralized nodule formation significantly. The present findings support the dual character of HMGB1 with anabolic therapeutic potential that might support the reestablishment of the structural and functional integrity of the periodontium following periodontal trauma such as orthodontic tooth movement.

  5. Nucleoplasmic Nup98 controls gene expression by regulating a DExH/D-box protein.

    Science.gov (United States)

    Capitanio, Juliana S; Montpetit, Ben; Wozniak, Richard W

    2018-01-01

    The nucleoporin Nup98 has been linked to the regulation of transcription and RNA metabolism, 1-3 but the mechanisms by which Nup98 contributes to these processes remains largely undefined. Recently, we uncovered interactions between Nup98 and several DExH/D-box proteins (DBPs), a protein family well-known for modulating gene expression and RNA metabolism. 4-6 Analysis of Nup98 and one of these DBPs, DHX9, showed that they directly interact, their association is facilitated by RNA, and Nup98 binding stimulates DHX9 ATPase activity. 7 Furthermore, these proteins were dependent on one another for their proper association with a subset of gene loci to control transcription and modulate mRNA splicing. 7 On the basis of these observations, we proposed that Nup98 functions to regulate DHX9 activity within the nucleoplasm. 7 Since Nup98 is associated with several DBPs, regulation of DHX9 by Nup98 may represent a paradigm for understanding how Nup98, and possibly other FG-Nup proteins, could direct the diverse cellular activities of multiple DBPs.

  6. A new F-box protein 7 gene mutation causing typical Parkinson's disease.

    Science.gov (United States)

    Lohmann, Ebba; Coquel, Anne-Sophie; Honoré, Aurélie; Gurvit, Hakan; Hanagasi, Hasmet; Emre, Murat; Leutenegger, Anne L; Drouet, Valérie; Sahbatou, Mourad; Guven, Gamze; Erginel-Unaltuna, Nihan; Deleuze, Jean-Francois; Lesage, Suzanne; Brice, Alexis

    2015-07-01

    Recessive mutations in the F-box protein 7 gene (FBXO7; PARK15) have been identified as a cause of the parkinsonian-pyramidal syndrome. Here, we report clinical and genetic findings in a Turkish family with novel FBXO7 mutations. Whole exome and targeted Sanger sequencing were performed for genetic analysis in a family with two members affected by Parkinson's disease (PD). All family members underwent detailed clinical, mental, and neurological examination. The new p.L34R (c.101 T>G) FBXO7 mutation was detected in a homozygous state in two Turkish sibs with typical levodopa-responsive PD. This is the first time a FBXO7 mutation has been identified that causes a phenotype compatible with typical idiopathic PD and presents with some of its common nonmotor features, such as rapid eye movement sleep behavior disorder, depression, and anxiety. © 2015 International Parkinson and Movement Disorder Society.

  7. Regulation of Autophagy-Related Protein and Cell Differentiation by High Mobility Group Box 1 Protein in Adipocytes

    Directory of Open Access Journals (Sweden)

    Huanhuan Feng

    2016-01-01

    Full Text Available High mobility group box 1 protein (HMGB1 is a molecule related to the development of inflammation. Autophagy is vital to maintain cellular homeostasis and protect against inflammation of adipocyte injury. Our recent work focused on the relationship of HMGB1 and autophagy in 3T3-L1 cells. In vivo experimental results showed that, compared with the normal-diet group, the high-fat diet mice displayed an increase in adipocyte size in the epididymal adipose tissues. The expression levels of HMGB1 and LC3II also increased in epididymal adipose tissues in high-fat diet group compared to the normal-diet mice. The in vitro results indicated that HMGB1 protein treatment increased LC3II formation in 3T3-L1 preadipocytes in contrast to that in the control group. Furthermore, LC3II formation was inhibited through HMGB1 knockdown by siRNA. Treatment with the HMGB1 protein enhanced LC3II expression after 2 and 4 days but decreased the expression after 8 and 10 days among various differentiation stages of adipocytes. By contrast, FABP4 expression decreased on the fourth day and increased on the eighth day. Hence, the HMGB1 protein modulated autophagy-related proteins and lipid-metabolism-related genes in adipocytes and could be a new target for treatment of obesity and related metabolic diseases.

  8. Differential stability of TATA box binding proteins from archaea with different optimal growth temperatures

    Science.gov (United States)

    Kopitz, Annette; Soppa, Jörg; Krejtschi, Carsten; Hauser, Karin

    2009-09-01

    The TATA box binding protein (TBP) is involved in promoter recognition, the first step of transcription initiation. TBP is universally conserved and essential in archaea and eukaryotes. In archaea, TBPs have to be stable and to function in species that cover an extremely wide range of optimal growth temperatures (OGTs), from below 0 °C to more than 100 °C. Thus, the archaeal TBP family is ideally suited to study the evolutionary adaptation of proteins to an extremely wide range of temperatures. We characterized the thermostability of one mesophilic and one thermophilic TBP by infrared spectroscopy. Transition temperatures ( Tms) of thermal unfolding have been determined using TBPs from Methanosarcina mazei (OGT 37 °C) and from Methanothermobacter thermautotrophicus (OGT 65 °C). Furthermore, the influence of protein and salt concentration on thermostability has been characterized. Together with previous studies, our results reveal that the Tms of archaeal TBPs are closely correlated with the OGTs of the respective species. Noteworthy, this is also true for the TBP from M. mazei representing the first characterized TBP from a mesophilic archaeon. In contrast, the only characterized eukaryotic TBP of the mesophilic plant Arabidopsis thaliana has a Tm more than 40 °C above the OGT.

  9. Potentiation of NMDA receptor-dependent cell responses by extracellular high mobility group box 1 protein.

    Directory of Open Access Journals (Sweden)

    Marco Pedrazzi

    Full Text Available BACKGROUND: Extracellular high mobility group box 1 (HMGB1 protein can operate in a synergistic fashion with different signal molecules promoting an increase of cell Ca(2+ influx. However, the mechanisms responsible for this effect of HMGB1 are still unknown. PRINCIPAL FINDINGS: Here we demonstrate that, at concentrations of agonist per se ineffective, HMGB1 potentiates the activation of the ionotropic glutamate N-methyl-D-aspartate receptor (NMDAR in isolated hippocampal nerve terminals and in a neuroblastoma cell line. This effect was abolished by the NMDA channel blocker MK-801. The HMGB1-facilitated NMDAR opening was followed by activation of the Ca(2+-dependent enzymes calpain and nitric oxide synthase in neuroblastoma cells, resulting in an increased production of NO, a consequent enhanced cell motility, and onset of morphological differentiation. We have also identified NMDAR as the mediator of HMGB1-stimulated murine erythroleukemia cell differentiation, induced by hexamethylenebisacetamide. The potentiation of NMDAR activation involved a peptide of HMGB1 located in the B box at the amino acids 130-139. This HMGB1 fragment did not overlap with binding sites for other cell surface receptors of HMGB1, such as the advanced glycation end products or the Toll-like receptor 4. Moreover, in a competition assay, the HMGB1((130-139 peptide displaced the NMDAR/HMGB1 interaction, suggesting that it comprised the molecular and functional site of HMGB1 regulating the NMDA receptor complex. CONCLUSION: We propose that the multifunctional cytokine-like molecule HMGB1 released by activated, stressed, and damaged or necrotic cells can facilitate NMDAR-mediated cell responses, both in the central nervous system and in peripheral tissues, independently of other known cell surface receptors for HMGB1.

  10. Immunoregulatory Forkhead Box Protein p3-Positive Lymphocytes Are Associated with Overall Survival in Patients with Pancreatic Neuroendocrine Tumors

    NARCIS (Netherlands)

    Reuver, P.R.; Mehta, S.; Gill, P.; Andrici, J.; D'Urso, L.; Clarkson, A.; Mittal, A.; Hugh, T.J.; Samra, J.S.; Gill, A.J.

    2016-01-01

    BACKGROUND: Forkhead box protein p3-positive (FoxP3(+)) regulatory T cells (Tregs) suppress host T-cell-mediated immune responses, limit surveillance against cancers, and have been associated with a poor prognosis. STUDY DESIGN: This study aims to identify the prognostic significance of FoxP3(+)

  11. Contributions of high mobility group box protein in experimental and clinical acute lung injury.

    Science.gov (United States)

    Ueno, Hiroshi; Matsuda, Tomoyuki; Hashimoto, Satoru; Amaya, Fumimasa; Kitamura, Yoshihiro; Tanaka, Masaki; Kobayashi, Atsuko; Maruyama, Ikuro; Yamada, Shingo; Hasegawa, Naoki; Soejima, Junko; Koh, Hidefumi; Ishizaka, Akitoshi

    2004-12-15

    This study was performed to examine the putative role of high mobility group box (HMGB) protein in the pathogenesis of acute lung injury (ALI). Observations were made (1) in 21 patients who were septic with ALI and 15 patients with normal lung function and (2) in a mouse model 24 hours after intratracheal instillation of lipopolysaccharide (LPS). The concentrations of HMGB1 were increased in plasma and lung epithelial lining fluid of patients with ALI and mice instilled with LPS. LPS-induced ALI was mitigated by anti-HMGB1 antibody. Although this protein was not detected in the plasma of control humans or mice, the concentrations of HMGB1 in lung epithelial lining fluid or in bronchoalveolar lavage fluid were unexpectedly high. The nuclear expression of HMGB1 was apparent in epithelial cells surrounding terminal bronchioles in normal mice, whereas its nuclear and cytoplasmic expression was observed in alveolar macrophages in LPS-instilled mice. Lung instillation of HMGB2 did not cause as much inflammation as HMGB1. Extracellular HMGB1 may play a key role in the pathogenesis of clinical and experimental ALI. However, its expression in normal airways is noteworthy and suggests that it also plays a physiologic role in the lung.

  12. The Y-Box Binding Protein 1 Suppresses Alzheimer's Disease Progression in Two Animal Models.

    Science.gov (United States)

    Bobkova, N V; Lyabin, D N; Medvinskaya, N I; Samokhin, A N; Nekrasov, P V; Nesterova, I V; Aleksandrova, I Y; Tatarnikova, O G; Bobylev, A G; Vikhlyantsev, I M; Kukharsky, M S; Ustyugov, A A; Polyakov, D N; Eliseeva, I A; Kretov, D A; Guryanov, S G; Ovchinnikov, L P

    2015-01-01

    The Y-box binding protein 1 (YB-1) is a member of the family of DNA- and RNA binding proteins. It is involved in a wide variety of DNA/RNA-dependent events including cell proliferation and differentiation, stress response, and malignant cell transformation. Previously, YB-1 was detected in neurons of the neocortex and hippocampus, but its precise role in the brain remains undefined. Here we show that subchronic intranasal injections of recombinant YB-1, as well as its fragment YB-11-219, suppress impairment of spatial memory in olfactory bulbectomized (OBX) mice with Alzheimer's type degeneration and improve learning in transgenic 5XFAD mice used as a model of cerebral amyloidosis. YB-1-treated OBX and 5XFAD mice showed a decreased level of brain β-amyloid. In OBX animals, an improved morphological state of neurons was revealed in the neocortex and hippocampus; in 5XFAD mice, a delay in amyloid plaque progression was observed. Intranasally administered YB-1 penetrated into the brain and could enter neurons. In vitro co-incubation of YB-1 with monomeric β-amyloid (1-42) inhibited formation of β-amyloid fibrils, as confirmed by electron microscopy. This suggests that YB-1 interaction with β-amyloid prevents formation of filaments that are responsible for neurotoxicity and neuronal death. Our data are the first evidence for a potential therapeutic benefit of YB-1 for treatment of Alzheimer's disease.

  13. The Y-Box Binding Protein 1 Suppresses Alzheimer's Disease Progression in Two Animal Models.

    Directory of Open Access Journals (Sweden)

    N V Bobkova

    Full Text Available The Y-box binding protein 1 (YB-1 is a member of the family of DNA- and RNA binding proteins. It is involved in a wide variety of DNA/RNA-dependent events including cell proliferation and differentiation, stress response, and malignant cell transformation. Previously, YB-1 was detected in neurons of the neocortex and hippocampus, but its precise role in the brain remains undefined. Here we show that subchronic intranasal injections of recombinant YB-1, as well as its fragment YB-11-219, suppress impairment of spatial memory in olfactory bulbectomized (OBX mice with Alzheimer's type degeneration and improve learning in transgenic 5XFAD mice used as a model of cerebral amyloidosis. YB-1-treated OBX and 5XFAD mice showed a decreased level of brain β-amyloid. In OBX animals, an improved morphological state of neurons was revealed in the neocortex and hippocampus; in 5XFAD mice, a delay in amyloid plaque progression was observed. Intranasally administered YB-1 penetrated into the brain and could enter neurons. In vitro co-incubation of YB-1 with monomeric β-amyloid (1-42 inhibited formation of β-amyloid fibrils, as confirmed by electron microscopy. This suggests that YB-1 interaction with β-amyloid prevents formation of filaments that are responsible for neurotoxicity and neuronal death. Our data are the first evidence for a potential therapeutic benefit of YB-1 for treatment of Alzheimer's disease.

  14. The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity to replication stress.

    Science.gov (United States)

    Zhang, You-Wei; Brognard, John; Coughlin, Chris; You, Zhongsheng; Dolled-Filhart, Marisa; Aslanian, Aaron; Manning, Gerard; Abraham, Robert T; Hunter, Tony

    2009-08-28

    ATR and Chk1 are two key protein kinases in the replication checkpoint. Activation of ATR-Chk1 has been extensively investigated, but checkpoint termination and replication fork restart are less well understood. Here, we report that DNA damage not only activates Chk1, but also exposes a degron-like region at the carboxyl terminus of Chk1 to an Fbx6-containing SCF (Skp1-Cul1-F box) E3 ligase, which mediates the ubiquitination and degradation of Chk1 and, in turn, terminates the checkpoint. The protein levels of Chk1 and Fbx6 showed an inverse correlation in both cultured cancer cells and in human breast tumor tissues. Further, we show that low levels of Fbx6 and consequent impairment of replication stress-induced Chk1 degradation are associated with cancer cell resistance to the chemotherapeutic agent, camptothecin. We propose that Fbx6-dependent Chk1 degradation contributes to S phase checkpoint termination and that a defect in this mechanism might increase tumor cell resistance to certain anticancer drugs.

  15. Increased serum levels of high mobility group box 1 protein in patients with autistic disorder.

    Science.gov (United States)

    Emanuele, Enzo; Boso, Marianna; Brondino, Natascia; Pietra, Stefania; Barale, Francesco; Ucelli di Nemi, Stefania; Politi, Pierluigi

    2010-05-30

    High mobility group box 1 (HMGB1) is a highly conserved, ubiquitous protein that functions as an activator for inducing the immune response and can be released from neurons after glutamate excitotoxicity. The objective of the present study was to measure serum levels of HMGB1 in patients with autistic disorder and to study their relationship with clinical characteristics. We enrolled 22 adult patients with autistic disorder (mean age: 28.1+/-7.7 years) and 28 age- and gender-matched healthy controls (mean age: 28.7+/-8.1 years). Serum levels of HMGB1 were measured by enzyme-linked immunosorbent assay (ELISA). Compared with healthy subjects, serum levels of HMGB1 were significantly higher in patients with autistic disorder (10.8+/-2.6 ng/mL versus 5.6+/-2.5 ng/mL, respectively, P<0.001). After adjustment for potential confounders, serum HMGB1 levels were independently associated with their domain A scores in the Autism Diagnostic Interview-Revised, which reflects their impairments in social interaction. These results suggest that HMGB1 levels may be affected in autistic disorder. Increased HMGB1 may be a biological correlate of the impaired reciprocal social interactions in this neurodevelopmental disorder. Copyright 2010 Elsevier Inc. All rights reserved.

  16. Apple F-box Protein MdMAX2 Regulates Plant Photomorphogenesis and Stress Response

    Directory of Open Access Journals (Sweden)

    Jian-Ping An

    2016-11-01

    Full Text Available MAX2 (MORE AXILLARY GROWTH2 is involved in diverse physiological processes, including photomorphogenesis, the abiotic stress response, as well as karrikin and strigolactone signaling-mediated shoot branching. In this study, MdMAX2, an F-box protein that is a homolog of Arabidopsis MAX2, was identified and characterized. Overexpression of MdMAX2 in apple calli enhanced the accumulation of anthocyanin. Ectopic expression of MdMAX2 in Arabidopsis exhibited photomorphogenesis phenotypes, including increased anthocyanin content and decreased hypocotyl length. Further study indicated that MdMAX2 might promote plant photomorphogenesis by affecting the auxin signaling as well as other plant hormones. Transcripts of MdMAX2 were noticeably up-regulated in response to NaCl and Mannitol treatments. Moreover, compared with the wild type, the MdMAX2-overexpressing apple calli and Arabidopsis exhibited increased tolerance to salt and drought stresses. Taken together, these results suggest that MdMAX2 plays a positive regulatory role in plant photomorphogenesis and stress response.

  17. Y-box protein-1/p18 fragment identifies malignancies in patients with chronic liver disease

    International Nuclear Information System (INIS)

    Tacke, Frank; Kanig, Nicolas; En-Nia, Abdelaziz; Kaehne, Thilo; Eberhardt, Christiane S; Shpacovitch, Victoria; Trautwein, Christian; Mertens, Peter R

    2011-01-01

    Immunohistochemical detection of cold shock proteins is predictive for deleterious outcome in various malignant diseases. We recently described active secretion of a family member, denoted Y-box (YB) protein-1. We tested the clinical and diagnostic value of YB-1 protein fragment p18 (YB-1/p18) detection in blood for malignant diseases. We used a novel monoclonal anti-YB-1 antibody to detect YB-1/p18 by immunoblotting in plasma samples of healthy volunteers (n = 33), patients with non-cancerous, mostly inflammatory diseases (n = 60), hepatocellular carcinoma (HCC; n = 25) and advanced solid tumors (n = 20). YB-1/p18 was then tested in 111 patients with chronic liver diseases, alongside established tumor markers and various diagnostic measures, during evaluation for potential liver transplantation. We developed a novel immunoblot to detect the 18 kD fragment of secreted YB-1 in human plasma (YB-1/p18) that contains the cold-shock domains (CSD) 1-3 of the full-length protein. YB-1/p18 was detected in 11/25 HCC and 16/20 advanced carcinomas compared to 0/33 healthy volunteers and 10/60 patients with non-cancerous diseases. In 111 patients with chronic liver disease, YB-1/p18 was detected in 20 samples. Its occurrence was not associated with advanced Child stages of liver cirrhosis or liver function. In this cohort, YB-1/p18 was not a good marker for HCC, but proved most powerful in detecting malignancies other than HCC (60% positive) with a lower rate of false-positive results compared to established tumor markers. Alpha-fetoprotein (AFP) was most sensitive in detecting HCC, but simultaneous assessment of AFP, CA19-9 and YB-1/p18 improved overall identification of HCC patients. Plasma YB-1/p18 can identify patients with malignancies, independent of acute inflammation, renal impairment or liver dysfunction. The detection of YB-1/p18 in human plasma may have potential as a tumor marker for screening of high-risk populations, e.g. before organ transplantation, and should

  18. A DNA-binding protein from Candida albicans that binds to the RPG box of Saccharomyces cerevisiae and the telomeric repeat sequence of C. albicans.

    Science.gov (United States)

    Ishii, N; Yamamoto, M; Lahm, H W; Iizumi, S; Yoshihara, F; Nakayama, H; Arisawa, M; Aoki, Y

    1997-02-01

    Electromobility shift assays with a DNA probe containing the Saccharomyces cerevisiae ENO1 RPG box identified a specific DNA-binding protein in total protein extracts of Candida albicans. The protein, named Rbf1p (RPG-box-binding protein 1), bound to other S. cerevisiae RPG boxes, although the nucleotide recognition profile was not completely the same as that of S. cerevisiae Rap 1p (repressor-activator protein 1), an RPG-box-binding protein. The repetitive sequence of the C. albicans chromosomal telomere also competed with RPG-box binding to Rbf1p. For further analysis, we purified Rbf1p 57,600-fold from C. albicans total protein extracts, raised mAbs against the purified protein and immunologically cloned the gene, whose ORF specified a protein of 527 aa. The bacterially expressed protein showed RPG-box-binding activity with the same profile as that of the purified one. The Rbf1p, containing two glutamine-rich regions that are found in many transcription factors, showed transcriptional activation capability in S. cerevisiae and was predominantly observed in nuclei. These results suggest that Rbf1p is a transcription factor with telomere-binding activity in C. albicans.

  19. Baculovirus F-Box Protein LEF-7 Modifies the Host DNA Damage Response To Enhance Virus Multiplication

    Science.gov (United States)

    Mitchell, Jonathan K.; Byers, Nathaniel M.

    2013-01-01

    The DNA damage response (DDR) of a host organism represents an effective antiviral defense that is frequently manipulated and exploited by viruses to promote multiplication. We report here that the large DNA baculoviruses, which require host DDR activation for optimal replication, encode a conserved replication factor, LEF-7, that manipulates the DDR via a novel mechanism. LEF-7 suppresses DDR-induced accumulation of phosphorylated host histone variant H2AX (γ-H2AX), a critical regulator of the DDR. LEF-7 was necessary and sufficient to block γ-H2AX accumulation caused by baculovirus infection or DNA damage induced by means of pharmacological agents. Deletion of LEF-7 from the baculovirus genome allowed γ-H2AX accumulation during virus DNA synthesis and impaired both very late viral gene expression and production of infectious progeny. Thus, LEF-7 is essential for efficient baculovirus replication. We determined that LEF-7 is a nuclear F-box protein that interacts with host S-phase kinase-associated protein 1 (SKP1), suggesting that LEF-7 acts as a substrate recognition component of SKP1/Cullin/F-box (SCF) complexes for targeted protein polyubiquitination. Site-directed mutagenesis demonstrated that LEF-7's N-terminal F-box is necessary for γ-H2AX repression and Autographa californica multiple nucleopolyhedrovirus (AcMNPV) replication events. We concluded that LEF-7 expedites virus replication most likely by selective manipulation of one or more host factors regulating the DDR, including γ-H2AX. Thus, our findings indicate that baculoviruses utilize a unique strategy among viruses for hijacking the host DDR by using a newly recognized F-box protein. PMID:24027328

  20. Successful immunotherapy of autoimmune cholangitis by adoptive transfer of forkhead box protein 3+ regulatory T cells

    Science.gov (United States)

    Tanaka, H; Zhang, W; Yang, G-X; Ando, Y; Tomiyama, T; Tsuneyama, K; Leung, P; Coppel, R L; Ansari, A A; Lian, Z X; Ridgway, W M; Joh, T; Gershwin, M E

    2014-01-01

    Treatment of primary biliary cirrhosis (PBC) has lagged behind that of other autoimmune diseases. In this study we have addressed the potential utility of immunotherapy using regulatory T cells (Treg) to treat murine autoimmune cholangitis. In particular, we have taken advantage of our ability to produce portal inflammation and bile duct cell loss by transfer of CD8+ T cells from the dominant negative form of transforming growth factor beta receptor type II (dnTGF-βRII) mice to recombination-activating gene (Rag)1–/– recipients. We then used this robust established adoptive transfer system and co-transferred CD8+ T cells from dnTGF-βRII mice with either C57BL/6 or dnTGF-βRII forkhead box protein 3 (FoxP3+) T cells. Recipient mice were monitored for histology, including portal inflammation and intralobular biliary cell damage, and also included a study of the phenotypical changes in recipient lymphoid populations and local and systemic cytokine production. Importantly, we report herein that adoptive transfer of Treg from C57BL/6 but not dnTGF-βRII mice significantly reduced the pathology of autoimmune cholangitis, including decreased portal inflammation and bile duct damage as well as down-regulation of the secondary inflammatory response. Further, to define the mechanism of action that explains the differential ability of C57BL/6 Treg versus dnTGF-βRII Treg on the ability to down-regulate autoimmune cholangitis, we noted significant differential expression of glycoprotein A repetitions predominant (GARP), CD73, CD101 and CD103 and a functionally significant increase in interleukin (IL)-10 in Treg from C57BL/6 compared to dnTGF-βRII mice. Our data reflect the therapeutic potential of wild-type CD4+ FoxP3+ Treg in reducing the excessive T cell responses of autoimmune cholangitis, which has significance for the potential immunotherapy of PBC. PMID:25041369

  1. Successful immunotherapy of autoimmune cholangitis by adoptive transfer of forkhead box protein 3(+) regulatory T cells.

    Science.gov (United States)

    Tanaka, H; Zhang, W; Yang, G-X; Ando, Y; Tomiyama, T; Tsuneyama, K; Leung, P; Coppel, R L; Ansari, A A; Lian, Z X; Ridgway, W M; Joh, T; Gershwin, M E

    2014-11-01

    Treatment of primary biliary cirrhosis (PBC) has lagged behind that of other autoimmune diseases. In this study we have addressed the potential utility of immunotherapy using regulatory T cells (Treg ) to treat murine autoimmune cholangitis. In particular, we have taken advantage of our ability to produce portal inflammation and bile duct cell loss by transfer of CD8(+) T cells from the dominant negative form of transforming growth factor beta receptor type II (dnTGF-βRII) mice to recombination-activating gene (Rag)1(-/-) recipients. We then used this robust established adoptive transfer system and co-transferred CD8(+) T cells from dnTGF-βRII mice with either C57BL/6 or dnTGF-βRII forkhead box protein 3 (FoxP3(+) ) T cells. Recipient mice were monitored for histology, including portal inflammation and intralobular biliary cell damage, and also included a study of the phenotypical changes in recipient lymphoid populations and local and systemic cytokine production. Importantly, we report herein that adoptive transfer of Treg from C57BL/6 but not dnTGF-βRII mice significantly reduced the pathology of autoimmune cholangitis, including decreased portal inflammation and bile duct damage as well as down-regulation of the secondary inflammatory response. Further, to define the mechanism of action that explains the differential ability of C57BL/6 Treg versus dnTGF-βRII Treg on the ability to down-regulate autoimmune cholangitis, we noted significant differential expression of glycoprotein A repetitions predominant (GARP), CD73, CD101 and CD103 and a functionally significant increase in interleukin (IL)-10 in Treg from C57BL/6 compared to dnTGF-βRII mice. Our data reflect the therapeutic potential of wild-type CD4(+) FoxP3(+) Treg in reducing the excessive T cell responses of autoimmune cholangitis, which has significance for the potential immunotherapy of PBC. © 2014 British Society for Immunology.

  2. Non–SCF-type F-box protein Roy1/Ymr258c interacts with a Rab5-like GTPase Ypt52 and inhibits Ypt52 function

    OpenAIRE

    Liu, Yuan; Nakatsukasa, Kunio; Kotera, Michiko; Kanada, Akira; Nishimura, Takashi; Kishi, Tsutomu; Mimura, Satoru; Kamura, Takumi

    2011-01-01

    Skp1/Cul1/F-box (SCF)–type F-box proteins are a component of the Cullin-RING SCF ubiquitin E3 ligase, which is involved in numerous cellular processes. However, the function of non–SCF-type F-box proteins remains largely unknown. The Rab5-like small guanosine 5′-triphosphatase Vps21/Ypt51 is a key regulator of intracellular transportation; however, deletion of its isoforms, Ypt52 and Ypt53, results in only a modest inhibition of intracellular trafficking. The function of these proteins theref...

  3. The divergently transcribed genes encoding yeast ribosomal proteins L46 and S24 are activated by shared RPG-boxes.

    Science.gov (United States)

    Kraakman, L S; Mager, W H; Maurer, K T; Nieuwint, R T; Planta, R J

    1989-12-11

    Transcription of the majority of the ribosomal protein (rp) genes in yeast is activated through common cis-acting elements, designated RPG-boxes. These elements have been shown to act as specific binding sites for the protein factor TUF/RAP1/GRF1 in vitro. Two such elements occur in the intergenic region separating the divergently transcribed genes encoding L46 and S24. To investigate whether the two RPG-boxes mediate transcription activation of both the L46 and S24 gene, two experimental strategies were followed: cloning of the respective genes on multicopy vectors and construction of fusion genes. Cloning of the L46 + S24 gene including the intergenic region in a multicopy yeast vector indicated that both genes are transcriptionally active. Using constructs in which only the S24 or the L46 gene is present, with or without the intergenic region, we obtained evidence that the intergenic region is indispensable for transcription activation of either gene. To demarcate the element(s) responsible for this activation, fusions of the intergenic region in either orientation to the galK reporter gene were made. Northern analysis of the levels of hybrid mRNA demonstrated that the intergenic region can serve as an heterologous promoter when it is in the 'S24-orientation'. Surprisingly, however, when fused in the reverse orientation the intergenic region did hardly confer transcription activity on the fusion gene. Furthermore, a 274 bp FnuDII-FnuDII fragment from the intergenic region that contains the RPG-boxes, could replace the naturally occurring upstream activation site (UASrpg) of the L25 rp-gene only when inserted in the 'S24-orientation'. Removal of 15 bp from the FnuDII fragment appeared to be sufficient to obtain transcription activation in the 'L46 orientation' as well. Analysis of a construct in which the RPG-boxes were selectively deleted from the promoter region of the L46 gene indicated that the RPG-boxes are needed for efficient transcriptional activation of

  4. F-box protein RcyA controls turnover of the kinesin-7 motor KipA in Aspergillus nidulans.

    Science.gov (United States)

    Herrero, Saturnino; Takeshita, Norio; Fischer, Reinhard

    2014-08-01

    Fungal filamentous growth depends on continuous membrane insertion at the tip, the delivery of membrane-bound positional markers, and the secretion of enzymes for cell wall biosynthesis. This is achieved through exocytosis. At the same time, polarized growth requires membrane and protein recycling through endocytosis. Endocytic vesicles are thought to enter the protein degradation pathway or recycle their content to the cell surface. In Saccharomyces cerevisiae, the Rcy1 F-box protein is involved in the recycling process of a v-SNARE protein. We identified a Rcy1 orthologue, RcyA, in the filamentous fungus Aspergillus nidulans as a protein interacting with the KipA kinesin-7 motor protein in a yeast two-hybrid screen. The interaction was confirmed through bimolecular fluorescence complementation. RcyA possesses an F-box domain at the N terminus and a prenylation (CaaX) motif at the C terminus. RcyA shows also similarity to Sec10, a component of the exocyst complex. The RcyA protein localized to the hyphal tip and forming septa, likely through transportation on secretory vesicles and partially on early endosomes, but independently of KipA. Deletion of rcyA did not cause severe morphological changes but caused partial defects in the recycling of the SynA v-SNARE protein and the positioning of the cell end markers TeaA and TeaR. In addition, deletion of rcyA led to increased concentrations of the KipA protein, whereas the transcript concentration was unaffected. These results suggest that RcyA probably labels KipA for degradation and thereby controls the protein amount of KipA. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  5. A photo-responsive F-box protein FOF2 regulates floral initiation by promoting FLC expression in Arabidopsis.

    Science.gov (United States)

    He, Reqing; Li, Xinmei; Zhong, Ming; Yan, Jindong; Ji, Ronghuan; Li, Xu; Wang, Qin; Wu, Dan; Sun, Mengsi; Tang, Dongying; Lin, Jianzhong; Li, Hongyu; Liu, Bin; Liu, Hongtao; Liu, Xuanming; Zhao, Xiaoying; Lin, Chentao

    2017-09-01

    Floral initiation is regulated by various genetic pathways in response to light, temperature, hormones and developmental status; however, the molecular mechanisms underlying the interactions between different genetic pathways are not fully understood. Here, we show that the photoresponsive gene FOF2 (F-box of flowering 2) negatively regulates flowering. FOF2 encodes a putative F-box protein that interacts specifically with ASK14, and its overexpression results in later flowering under both long-day and short-day photoperiods. Conversely, transgenic plants expressing the F-box domain deletion mutant of FOF2 (FOF2ΔF), or double loss of function mutant of FOF2 and FOL1 (FOF2-LIKE 1) present early flowering phenotypes. The late flowering phenotype of the FOF2 overexpression lines is suppressed by the flc-3 loss-of-function mutation. Furthermore, FOF2 mRNA expression is regulated by autonomous pathway gene FCA, and the repressive effect of FOF2 in flowering can be overcome by vernalization. Interestingly, FOF2 expression is regulated by light. The protein level of FOF2 accumulates in response to light, whereas it is degraded under dark conditions via the 26S proteasome pathway. Our findings suggest a possible mechanistic link between light conditions and the autonomous floral promotion pathway in Arabidopsis. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  6. Protein interactions of MADS box transcription factors involved in flowering in Lolium perenne

    NARCIS (Netherlands)

    Ciannamea, S.; Kaufmann, K.; Frau, M.; Nougalli Tonaco, I.A.; Petersen, K.; Nielsen, K.K.; Angenent, G.C.; Immink, G.H.

    2006-01-01

    Regulation of flowering time is best understood in the dicot model species Arabidopsis thaliana. Molecular analyses revealed that genes belonging to the MADS box transcription factor family play pivotal regulatory roles in both the vernalization- and photoperiod-regulated flowering pathways. Here

  7. Forkhead Box Protein 1 (Foxa1) and the Sumoylation Pathway that Regulates Foxa1 Stability are Potential Targets for Breast Cancer Treatment

    National Research Council Canada - National Science Library

    Belaguli, Narasimhaswamy S

    2007-01-01

    .... In contrast to the related forkhead box protein A2 (Foxa2) in which the K6R mutation induced protein destabilization, mutation of the conserved K6 sumoylation site did not strongly affect the stability of the Foxa1 protein...

  8. Forkhead box protein O3 transcription factor negatively regulates autophagy in human cancer cells by inhibiting forkhead box protein O1 expression and cytosolic accumulation.

    Directory of Open Access Journals (Sweden)

    Wan Long Zhu

    Full Text Available FoxO proteins are important regulators in cellular metabolism and are recognized to be nodes in multiple signaling pathways, most notably those involving PI3K/AKT and mTOR. FoxO proteins primarily function as transcription factors, but recent study suggests that cytosolic FoxO1 participates in the regulation of autophagy. In the current study, we find that cytosolic FoxO1 indeed stimulates cellular autophagy in multiple cancer cell lines, and that it regulates not only basal autophagy but also that induced by rapamycin and that in response to nutrient deprivation. These findings illustrate the importance of FoxO1 in cell metabolism regulation independent of its transcription factor function. In contrast to FoxO1, we find the closely related FoxO3a is a negative regulator of autophagy in multiple cancer cell lines, a previously unrecognized function for this protein, different from its function in benign fibroblast and muscle cells. The induction of autophagy by the knockdown of FoxO3a was found not to be mediated through the suppression of mTORC1 signaling; rather, the regulatory role of FoxO3a on autophagy was determined to be through its ability to transcriptionally suppress FoxO1. This complicated interplay of FoxO1 and FoxO3a suggests a complex checks- and balances-relationship between FoxO3a and FoxO1 in regulating autophagy and cell metabolism.

  9. A Role for the F-Box Protein HAWAIIAN SKIRT in Plant microRNA Function.

    Science.gov (United States)

    Lang, Patricia L M; Christie, Michael D; Dogan, Ezgi S; Schwab, Rebecca; Hagmann, Jörg; van de Weyer, Anna-Lena; Scacchi, Emanuele; Weigel, Detlef

    2018-01-01

    As regulators of gene expression in multicellular organisms, microRNAs (miRNAs) are crucial for growth and development. Although a plethora of factors involved in their biogenesis and action in Arabidopsis ( Arabidopsis thaliana ) has been described, these processes and their fine-tuning are not fully understood. Here, we used plants expressing an artificial miRNA target mimic (MIM) to screen for negative regulators of miR156. We identified a new mutant allele of the F-box gene HAWAIIAN SKIRT ( HWS ; At3G61590), hws - 5 , as a suppressor of the MIM156 -induced developmental and molecular phenotypes. In hws plants, levels of some endogenous miRNAs are increased and their mRNA targets decreased. Plants constitutively expressing full-length HWS-but not a truncated version lacking the F-box domain-display morphological and molecular phenotypes resembling those of mutants defective in miRNA biogenesis and activity. In combination with such mutants, hws loses its delayed floral organ abscission ("skirt") phenotype, suggesting epistasis. Also, the hws transcriptome profile partially resembles those of well-known miRNA mutants hyl1 - 2 , se - 3 , and ago1 - 27 , pointing to a role in a common pathway. We thus propose HWS as a novel, F-box dependent factor involved in miRNA function. © 2018 American Society of Plant Biologists. All Rights Reserved.

  10. Iron-regulatory proteins DmdR1 and DmdR2 of Streptomyces coelicolor form two different DNA-protein complexes with iron boxes.

    OpenAIRE

    Flores, Francisco J; Martín, Juan F

    2004-01-01

    In high G+C Gram-positive bacteria, the control of expression of genes involved in iron metabolism is exerted by a DmdR [divalent (bivalent) metal-dependent regulatory protein] in the presence of Fe2+ or other bivalent ions. The dmdR1 and dmdR2 genes of Streptomyces coelicolor were overexpressed in Escherichia coli and the DmdR1 and DmdR2 proteins were purified to homogeneity. Electrophoretic mobility-shift assays showed that both DmdR1 and DmdR2 bind to the 19-nt tox and desA iron boxes form...

  11. Deadly medicine.

    Science.gov (United States)

    Bachrach, Susan

    2007-01-01

    This article discusses the methods the United States Holocaust Memorial Museum used to make an exhibition on the complex history of Nazi eugenics accessible to the museum's mass public and at the same time, provocative for special audiences consisting of professionals and students from the biomedical fields. Deadly Medicine: Creating the Master Race showed how both eugenics and related "euthanasia" programs in Nazi Germany helped pave the road to the Holocaust. The exhibition implicitly evoked the present-day appeal of biological explanations for human behavior and of new visions of human perfection. Educational programs used the exhibition as a springboard for discussions of bioethics and medical ethics.

  12. A calmodulin-binding/CGCG box DNA-binding protein family involved in multiple signaling pathways in plants

    Science.gov (United States)

    Yang, Tianbao; Poovaiah, B. W.

    2002-01-01

    We reported earlier that the tobacco early ethylene-responsive gene NtER1 encodes a calmodulin-binding protein (Yang, T., and Poovaiah, B. W. (2000) J. Biol. Chem. 275, 38467-38473). Here we demonstrate that there is one NtER1 homolog as well as five related genes in Arabidopsis. These six genes are rapidly and differentially induced by environmental signals such as temperature extremes, UVB, salt, and wounding; hormones such as ethylene and abscisic acid; and signal molecules such as methyl jasmonate, H(2)O(2), and salicylic acid. Hence, they were designated as AtSR1-6 (Arabidopsis thaliana signal-responsive genes). Ca(2+)/calmodulin binds to all AtSRs, and their calmodulin-binding regions are located on a conserved basic amphiphilic alpha-helical motif in the C terminus. AtSR1 targets the nucleus and specifically recognizes a novel 6-bp CGCG box (A/C/G)CGCG(G/T/C). The multiple CGCG cis-elements are found in promoters of genes such as those involved in ethylene signaling, abscisic acid signaling, and light signal perception. The DNA-binding domain in AtSR1 is located on the N-terminal 146 bp where all AtSR1-related proteins share high similarity but have no similarity to other known DNA-binding proteins. The calmodulin-binding nuclear proteins isolated from wounded leaves exhibit specific CGCG box DNA binding activities. These results suggest that the AtSR gene family encodes a family of calmodulin-binding/DNA-binding proteins involved in multiple signal transduction pathways in plants.

  13. A human Polycomb isoform lacking the Pc box does not participate to PRC1 complexes but forms protein assemblies and represses transcription

    DEFF Research Database (Denmark)

    Völkel, Pamela; Le Faou, Perrine; Vandamme, Julien

    2012-01-01

    and alternative splicing events, the human CBX2 locus produces two transcripts: a 5-exon transcript that encodes the 532-amino acid CBX2-1 isoform that contains the conserved chromodomain and Pc box and a 4-exon transcript encoding a shorter isoform, CBX2-2, lacking the Pc box but still possessing a chromodomain....... Using biochemical approaches and a novel in vivo imaging assay, we show that the short CBX2-2 isoform lacking the Pc box, does not participate in PRC1 protein complexes, but self-associates in vivo and forms complexes of high molecular weight. Furthermore, the CBX2 short isoform is still able to repress...

  14. Identifying the substrate proteins of U-box E3s E4B and CHIP by orthogonal ubiquitin transfer.

    Science.gov (United States)

    Bhuripanyo, Karan; Wang, Yiyang; Liu, Xianpeng; Zhou, Li; Liu, Ruochuan; Duong, Duc; Zhao, Bo; Bi, Yingtao; Zhou, Han; Chen, Geng; Seyfried, Nicholas T; Chazin, Walter J; Kiyokawa, Hiroaki; Yin, Jun

    2018-01-01

    E3 ubiquitin (UB) ligases E4B and carboxyl terminus of Hsc70-interacting protein (CHIP) use a common U-box motif to transfer UB from E1 and E2 enzymes to their substrate proteins and regulate diverse cellular processes. To profile their ubiquitination targets in the cell, we used phage display to engineer E2-E4B and E2-CHIP pairs that were free of cross-reactivity with the native UB transfer cascades. We then used the engineered E2-E3 pairs to construct "orthogonal UB transfer (OUT)" cascades so that a mutant UB (xUB) could be exclusively used by the engineered E4B or CHIP to label their substrate proteins. Purification of xUB-conjugated proteins followed by proteomics analysis enabled the identification of hundreds of potential substrates of E4B and CHIP in human embryonic kidney 293 cells. Kinase MAPK3 (mitogen-activated protein kinase 3), methyltransferase PRMT1 (protein arginine N -methyltransferase 1), and phosphatase PPP3CA (protein phosphatase 3 catalytic subunit alpha) were identified as the shared substrates of the two E3s. Phosphatase PGAM5 (phosphoglycerate mutase 5) and deubiquitinase OTUB1 (ovarian tumor domain containing ubiquitin aldehyde binding protein 1) were confirmed as E4B substrates, and β-catenin and CDK4 (cyclin-dependent kinase 4) were confirmed as CHIP substrates. On the basis of the CHIP-CDK4 circuit identified by OUT, we revealed that CHIP signals CDK4 degradation in response to endoplasmic reticulum stress.

  15. Molecular Cloning of a cDNA Encoding for Taenia solium TATA-Box Binding Protein 1 (TsTBP1) and Study of Its Interactions with the TATA-Box of Actin 5 and Typical 2-Cys Peroxiredoxin Genes.

    Science.gov (United States)

    Rodríguez-Lima, Oscar; García-Gutierrez, Ponciano; Jiménez, Lucía; Zarain-Herzberg, Ángel; Lazzarini, Roberto; Landa, Abraham

    2015-01-01

    TATA-box binding protein (TBP) is an essential regulatory transcription factor for the TATA-box and TATA-box-less gene promoters. We report the cloning and characterization of a full-length cDNA that encodes a Taenia solium TATA-box binding protein 1 (TsTBP1). Deduced amino acid composition from its nucleotide sequence revealed that encodes a protein of 238 residues with a predicted molecular weight of 26.7 kDa, and a theoretical pI of 10.6. The NH2-terminal domain shows no conservation when compared with to pig and human TBP1s. However, it shows high conservation in size and amino acid identity with taeniids TBP1s. In contrast, the TsTBP1 COOH-terminal domain is highly conserved among organisms, and contains the amino acids involved in interactions with the TATA-box, as well as with TFIIA and TFIIB. In silico TsTBP1 modeling reveals that the COOH-terminal domain forms the classical saddle structure of the TBP family, with one α-helix at the end, not present in pig and human. Native TsTBP1 was detected in T. solium cysticerci´s nuclear extract by western blot using rabbit antibodies generated against two synthetic peptides located in the NH2 and COOH-terminal domains of TsTBP1. These antibodies, through immunofluorescence technique, identified the TBP1 in the nucleus of cells that form the bladder wall of cysticerci of Taenia crassiceps, an organism close related to T. solium. Electrophoretic mobility shift assays using nuclear extracts from T. solium cysticerci and antibodies against the NH2-terminal domain of TsTBP1 showed the interaction of native TsTBP1 with the TATA-box present in T. solium actin 5 (pAT5) and 2-Cys peroxiredoxin (Ts2-CysPrx) gene promoters; in contrast, when antibodies against the anti-COOH-terminal domain of TsTBP1 were used, they inhibited the binding of TsTBP1 to the TATA-box of the pAT5 promoter gene.

  16. Antiapoptotic Effect of Recombinant HMGB1 A-box Protein via Regulation of microRNA-21 in Myocardial Ischemia-Reperfusion Injury Model in Rats.

    Science.gov (United States)

    Han, Qiang; Zhang, Hua-Yong; Zhong, Bei-Long; Zhang, Bing; Chen, Hua

    2016-04-01

    The ~80 amino acid A box DNA-binding domain of high mobility group box 1 (HMGB1) protein antagonizes proinflammatory responses during myocardial ischemia reperfusion (I/R) injury. The exact role of microRNA-21 (miR-21) is unknown, but its altered levels are evident in I/R injury. This study examined the roles of HMGB1 A-box and miR-21 in rat myocardial I/R injury model. Sixty Sprague-Dawley rats were randomly divided into six equal groups: (1) Sham; (2) I/R; (3) Ischemic postconditioning (IPost); (4) AntagomiR-21 post-treatment; (5) Recombinant HMGB1 A-box pretreatment; and (6) Recombinant HMGB1 A-box + antagomiR-21 post-treatment. Hemodynamic indexes, arrhythmia scores, ischemic area and infarct size, myocardial injury, and related parameters were studied. Expression of miR-21 was detected by real-time quantitative polymerase chain reaction (qRT-PCR) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to quantify apoptosis. Left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal rate of pressure rise (+dp/dtmax), and decline (-dp/dtmax) showed clear reduction upon treatment with recombinant HMGB1 A-box. Arrhythmia was relieved and infarct area decreased in the group pretreated with recombinant HMGB1 A-box, compared with other groups. Circulating lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels increased in response to irreversible cellular injury, while creatine kinase MB isoenzymes (CK-MB) and superoxide dismutase (SOD) activities were reduced in the I/R group, which was reversed following recombinant HMGB1 A-box treatment. Interestingly, pretreatment with recombinant HMGB1 A-box showed the most dramatic reductions in miR-21 levels, compared with other groups. Significantly reduced apoptotic index (AI) was seen in recombinant HMGB1 A-box pretreatment group and recombinant HMGB1 A-box + antagomiR-21 post-treatment group, with the former showing a more

  17. Cyclin-like F-box protein plays a role in growth and development of the three model species Medicago truncatula, Lotus japonicus, and Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Boycheva I

    2015-08-01

    Full Text Available Irina Boycheva,1 Valya Vassileva,2 Miglena Revalska,1 Grigor Zehirov,2 Anelia Iantcheva1 1Department of Functional Genetics Legumes, 2AgroBioInstitute, Department of Plant Stress Molecular Biology, Institute of Plant Physiology and Genetics, Sofia, Bulgaria Abstract: In eukaryotes, F-box proteins are one of the main components of the SCF complex that belongs to the family of ubiquitin E3 ligases, which catalyze protein ubiquitination and maintain the balance between protein synthesis and degradation. In the present study, we clarified the role and function of the gene encoding cyclin-like F-box protein from Medicago truncatula using transgenic plants of the model species M. truncatula, Lotus japonicas, and Arabidopsis thaliana generated by Agrobacterium-mediated transformation. Morphological and transcriptional analyses combined with flow cytometry and histochemistry demonstrated the participation of this protein in many aspects of plant growth and development, including processes of indirect somatic embryogenesis and symbiotic nodulation. The cyclin-like F-box gene showed expression in all plant organs and tissues comprised of actively dividing cells. The observed variations in root and hypocotyl growth, leaf and silique development, ploidy levels, and leaf parameters in the obtained transgenic lines demonstrated the effects of this gene on organ development. Furthermore, knockdown of cyclin-like F-box led to accumulation of higher levels of the G2/M transition-specific gene cyclin B1:1 (CYCB1:1, suggesting its possible role in cell cycle control. Together, the collected data suggest a similar role of the cyclin-like F-box protein in the three model species, providing evidence for the functional conservation of the studied gene. Keywords: cyclin-like F-box, model legumes, Arabidopsis thaliana, plant growth, plant development, cell cycle

  18. Evaluation of cyclooxygenase protein expression in traumatized versus normal tissues from eastern box turtles (Terrapene carolina carolina).

    Science.gov (United States)

    Royal, Lillian W; Lascelles, B Duncan X; Lewbart, Gregory A; Correa, Maria T; Jones, Samuel L

    2012-06-01

    This pilot study was designed to determine whether cyclooxygenase (COX)-1, COX-2, or both are expressed in normal turtle tissues and whether level of expression changes when tissue becomes inflamed. Five eastern box turtles, Terrapene carolina carolina, that either died or were euthanatized due to disease or injuries were used for this work. Tissues were obtained from the five turtles. Western blot analysis was used to evaluate tissues for COX-1 and COX-2 proteins. Densiometric analysis was used to compare Western blot bands within each turtle. COX-1 and COX-2 were found in the liver, kidney, grossly normal muscle, and grossly traumatized (inflamed) muscle of all study turtles. In all cases, COX-1 and COX-2 proteins were increased in traumatized muscle over grossly normal nontraumatized muscle. The highest levels of COX-1 and COX-2 proteins were found in kidney and liver. There was no statistical difference between the amount of COX-1 protein in liver and kidney, but traumatized muscle compared with grossly normal muscle had significantly greater COX-1 but not COX 2 protein concentrations. There was no statistical difference between the amount of COX-2 protein in liver and kidney. Traumatized muscle expressed nonstatistically significant greater amounts of COX-2 compared with grossly normal muscle. COX-1 and COX-2 proteins are expressed in turtle tissues, and both isoforms are upregulated during inflammation of muscle tissue. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) that block both COX isoforms might be more efficacious than COX-2-selective drugs. This work suggests that NSAIDs should be evaluated for potential liver and kidney toxicity in turtles.

  19. Plasma electrophoretic profiles and hemoglobin binding protein reference intervals in the eastern box turtle (Terrapene carolina carolina) and influences of age, sex, season, and location.

    Science.gov (United States)

    Flower, Jennifer E; Byrd, John; Cray, Carolyn; Allender, Matthew C

    2014-12-01

    Evaluation of plasma electrophoretic profiles and acute phase protein concentrations may play a valuable role in health assessment of reptiles; however, little is known about reference intervals in free-ranging eastern box turtles (Terrapene carolina carolina). The purpose of this study was to establish reference intervals of protein electrophoretic profiles and hemoglobin binding protein ([HBP] as determined by a haptoglobin assay) in free-ranging eastern box turtles and to assess any possible correlations between varying age class (adults vs. juvenile), sex (male, female, or unknown), season (spring, summer, or fall), or location (Tennessee vs. Illinois). Blood samples were obtained from 324 eastern box turtles from 2010 to 2012 at three sites in Illinois and one site in Tennessee, USA. Significant differences were observed with total protein (sex, season, state, Illinois location), albumin (age class, season, state, Illinois location), α-1 globulins (sex, season, Illinois location), α-2 globulins (sex, season, state, Illinois location), β globulins (age class, sex, season, state, Illinois location), γ globulins (sex, season state, Illinois location), and hemoglobin binding protein (age class, sex, state, Illinois location). The use of electrophoretic profiles and acute phase proteins is a relatively new concept in reptilian medicine, and this study allowed for establishment of references intervals in the eastern box turtle and emphasized differences that occured based on age, sex, season, and location. Future research in this area can now build on these data to determine changes in population health over time or alterations due to specific environmental or disease threats.

  20. Neuronal expression of TATA box-binding protein containing expanded polyglutamine in knock-in mice reduces chaperone protein response by impairing the function of nuclear factor-Y transcription factor.

    Science.gov (United States)

    Huang, Shanshan; Ling, Joseph J; Yang, Su; Li, Xiao-Jiang; Li, Shihua

    2011-07-01

    The polyglutamine diseases consist of nine neurodegenerative disorders including spinocerebellar ataxia type 17 that is caused by a polyglutamine tract expansion in the TATA box-binding protein. In all polyglutamine diseases, polyglutamine-expanded proteins are ubiquitously expressed throughout the body but cause selective neurodegeneration. Understanding the specific effects of polyglutamine-expanded proteins, when expressed at the endogenous levels, in neurons is important for unravelling the pathogenesis of polyglutamine diseases. However, addressing this important issue using mouse models that either overly or ubiquitously express mutant polyglutamine proteins in the brain and body has proved difficult. To investigate the pathogenesis of spinocerebellar ataxia 17, we generated a conditional knock-in mouse model that expresses one copy of the mutant TATA box-binding protein gene, which encodes a 105-glutamine repeat, selectively in neuronal cells at the endogenous level. Neuronal expression of mutant TATA box-binding protein causes age-dependent neurological symptoms in mice and the degeneration of cerebellar Purkinje cells. Mutant TATA box-binding protein binds more tightly to the transcription factor nuclear factor-Y, inhibits its association with the chaperone protein promoter, as well as the promoter activity and reduces the expression of the chaperones Hsp70, Hsp25 and HspA5, and their response to stress. These findings demonstrate how mutant TATA box-binding protein at the endogenous level affects neuronal function, with important implications for the pathogenesis and treatment of polyglutamine diseases.

  1. A bifunctional archaeal protein that is a component of 30S ribosomal subunits and interacts with C/D box small RNAs

    Directory of Open Access Journals (Sweden)

    Andrea Ciammaruconi

    2008-01-01

    Full Text Available We have identified a novel archaeal protein that apparently plays two distinct roles in ribosome metabolism. It is a polypeptide of about 18 kDa (termed Rbp18 that binds free cytosolic C/D box sRNAs in vivo and in vitro and behaves as a structural ribosomal protein, specifically a component of the 30S ribosomal subunit. As Rbp18 is selectively present in Crenarcheota and highly thermophilic Euryarchaeota, we propose that it serves to protect C/D box sRNAs from degradation and perhaps to stabilize thermophilic 30S subunits.

  2. Deadly progress

    International Nuclear Information System (INIS)

    Nader, R.; Abbotts, J.

    1978-01-01

    Nuclear power plants are safe, they help to get through the future bottle-neck in the field of energy, nuclear power plants provide for cheap electrical power and support economic growth - these are the sedative formulae which have been used for years to close the populations eyes towards the real problems. In this book, the American lawyer Ralph Nader and the nuclear chemist John Abbots not only oppose this myth of atomic safety, but they also defeat this theory with numerous technical, economic, and political details. Having realized the fact that the development of atomic energy can no longer be prevented by warnings of independent experts, but only by massive protests by the population - i.e. the protest by informed persons-, they give an understandable introduction to the techniques of atomic energy, construction of nuclear power plants, radioactive radiation, safety, etc. Furthermore, they inform about the social, political, and economic background of the nuclear power forcing. Nader and Abbots show the uncertainty of science, they bring secret documents about failures already occured and point out the catastrophic consequences of possible defects. The result of the thorough study: A 'technologic Vietnam' impends both USA and all other nuclear power countries, if the population won't struggle against this dead-end programme of the governments. (orig./HP) [de

  3. Virtual Box

    DEFF Research Database (Denmark)

    Davis, Hilary; Skov, Mikael B.; Stougaard, Malthe

    2007-01-01

    . This paper reports on the design, implementation and initial evaluation of Virtual Box. Virtual Box attempts to create a physical and engaging context in order to support reciprocal interactions with expressive content. An implemented version of Virtual Box is evaluated in a location-aware environment...

  4. RNA polymerase II components and Rrn7 form a preinitiation complex on the HomolD box to promote ribosomal protein gene expression in Schizosaccharomyces pombe.

    Science.gov (United States)

    Montes, Matías; Moreira-Ramos, Sandra; Rojas, Diego A; Urbina, Fabiola; Käufer, Norbert F; Maldonado, Edio

    2017-02-01

    In Schizosaccharomyces pombe, ribosomal protein gene (RPG) promoters contain a TATA box analog, the HomolD box, which is bound by the Rrn7 protein. Despite the importance of ribosome biogenesis for cell survival, the mechanisms underlying RPG transcription remain unknown. In this study, we found that components of the RNA polymerase II (RNAPII) system, consisting of the initiation or general transcription factors (GTFs) TFIIA, IIB, IIE, TATA-binding protein (TBP) and the RNAPII holoenzyme, interacted directly with Rrn7 in vitro, and were able to form a preinitiation complex (PIC) on the HomolD box. PIC complex formation follows an ordered pathway on these promoters. The GTFs and RNAPII can also be cross-linked to HomolD-containing promoters in vivo. In an in vitro reconstituted transcription system, RNAPII components and Rrn7 were necessary for HomolD-directed transcription. The Mediator complex was required for basal transcription from those promoters in whole cell extract (WCE). The Med17 subunit of Mediator also can be cross-linked to the promoter region of HomolD-containing promoters in vivo, suggesting the presence of the Mediator complex on HomolD box-containing promoters. Together, these data show that components of the RNAPII machinery and Rrn7 participate in the PIC assembly on the HomolD box, thereby directing RPG transcription. © 2017 Federation of European Biochemical Societies.

  5. High mobility group box-1 protein in patients with suspected community-acquired infections and sepsis

    DEFF Research Database (Denmark)

    Gaïni, Shahin; Pedersen, Svend Stenvang; Koldkjær, Ole

    2007-01-01

    measured with a commercially available enzyme-linked immunosorbent assay (ELISA). Procalcitonin levels were measured with a TRACE (time-resolved amplified cryptate emission) assay. Lipopolysaccharide-binding protein and interleukin-6 were measured with a chemiluminiscent immunometric assay. Soluble...

  6. Love the dead, fear the dead

    DEFF Research Database (Denmark)

    Seebach, Sophie Hooge

    2017-01-01

    The dead are everywhere in the landscape in Acholi, northern Uganda. In the homes, the dead are present through their gravesites, situated next to houses and huts, and as spiritual presences in their family’s daily lives. In the bush, the dead are present as a constant potentiality, in the form o...

  7. Elr-type proteins protect Xenopus Dead end mRNA from miR-18-mediated clearance in the soma.

    Science.gov (United States)

    Koebernick, Katja; Loeber, Jana; Arthur, Patrick Kobina; Tarbashevich, Katsiaryna; Pieler, Tomas

    2010-09-14

    Segregation of the future germ line defines a crucial cell fate decision during animal development. In Xenopus, germ cells are specified by inheritance of vegetally localized maternal determinants, including a group of specific mRNAs. Here, we show that the vegetal localization elements (LE) of Xenopus Dead end (XDE) and of several other germ-line-specific, vegetally localized transcripts mediate germ cell-specific stabilization and somatic clearance of microinjected reporter mRNA in Xenopus embryos. The part of XDE-LE critical for somatic RNA clearance exhibits homology to zebrafish nanos1 and appears to be targeted by Xenopus miR-18 for somatic mRNA clearance. Xenopus Elr-type proteins of the vegetal localization complex can alleviate somatic RNA clearance of microinjected XDE-LE and endogenous XDE mRNA. ElrB1 synergizes with Xenopus Dead end protein in the stabilization of XDE-LE mRNA. Taken together, our findings unveil a functional link of vegetal mRNA localization and the protection of germ-line mRNAs from somatic clearance.

  8. The Agrobacterium tumefaciens virulence protein VirE3 is a transcriptional activator of the F-box gene VBF.

    Science.gov (United States)

    Niu, Xiaolei; Zhou, Meiliang; Henkel, Christiaan V; van Heusden, G Paul H; Hooykaas, Paul J J

    2015-12-01

    During Agrobacterium tumefaciens-mediated transformation of plant cells a part of the tumour-inducing plasmid, T-DNA, is integrated into the host genome. In addition, a number of virulence proteins are translocated into the host cell. The virulence protein VirE3 binds to the Arabidopsis thaliana pBrp protein, a plant-specific general transcription factor of the TFIIB family. To study a possible role for VirE3 in transcriptional regulation, we stably expressed virE3 in A. thaliana under control of a tamoxifen-inducible promoter. By RNA sequencing we showed that upon expression of virE3 the RNA levels of 607 genes were increased more than three-fold and those of 132 genes decreased more than three-fold. One of the strongly activated genes was that encoding VBF (At1G56250), an F-box protein that may affect the levels of the VirE2 and VIP1 proteins. Using Arabidopsis cell suspension protoplasts we showed that VirE3 stimulates the VBF promoter, especially when co-expressed with pBrp. Although pBrp is localized at the external surface of plastids, co-expression of VirE3 and pBrp in Arabidopsis cell suspension protoplasts resulted in the accumulation of pBrp in the nucleus. Our results suggest that VirE3 affects the transcriptional machinery of the host cell to favour the transformation process. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  9. Functional characterization of the ER stress induced X-box-binding protein-1 (Xbp-1 in the porcine system

    Directory of Open Access Journals (Sweden)

    Jin Dong-Il

    2011-05-01

    Full Text Available Abstract Background The unfolded protein response (UPR is an evolutionary conserved adaptive reaction for increasing cell survival under endoplasmic reticulum (ER stress conditions. X-box-binding protein-1 (Xbp1 is a key transcription factor of UPR that activates genes involved in protein folding, secretion, and degradation to restore ER function. The UPR induced by ER stress was extensively studied in diseases linked to protein misfolding and aggregations. However, in the porcine system, genes in the UPR pathway were not investigated. In this study, we isolated and characterized the porcine Xbp1 (pXbp1 gene in ER stress using porcine embryonic fibroblast (PEF cells and porcine organs. ER stress was induced by the treatment of tunicamycin and cell viability was investigated by the MTT assay. For cloning and analyzing the expression pattern of pXbp1, RT-PCR analysis and Western blot were used. Knock-down of pXbp1 was performed by the siRNA-mediated gene silencing. Results We found that the pXbp1 mRNA was the subject of the IRE1α-mediated unconventional splicing by ER stress. Knock-down of pXbp1 enhanced ER stress-mediated cell death in PEF cells. In adult organs, pXbp1 mRNA and protein were expressed and the spliced forms were detected. Conclusions It was first found that the UPR mechanisms and the function of pXbp1 in the porcine system. These results indicate that pXbp1 plays an important role during the ER stress response like other animal systems and open a new opportunity for examining the UPR pathway in the porcine model system.

  10. The expanding functions of cellular helicases: the tombusvirus RNA replication enhancer co-opts the plant eIF4AIII-like AtRH2 and the DDX5-like AtRH5 DEAD-box RNA helicases to promote viral asymmetric RNA replication.

    Directory of Open Access Journals (Sweden)

    Nikolay Kovalev

    2014-04-01

    Full Text Available Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC, template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3' terminal promoter region in the viral minus-strand (-RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5' proximal RIII(- replication enhancer (REN element in the TBSV (-RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (-RNA could unwind the dsRNA structure within the RIII(- REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(- REN in stimulation of plus-strand (+RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(- REN that promotes bringing the 5' and 3' terminal (-RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+-strand synthesis, thus resulting in asymmetrical viral replication.

  11. The expanding functions of cellular helicases: the tombusvirus RNA replication enhancer co-opts the plant eIF4AIII-like AtRH2 and the DDX5-like AtRH5 DEAD-box RNA helicases to promote viral asymmetric RNA replication.

    Science.gov (United States)

    Kovalev, Nikolay; Nagy, Peter D

    2014-04-01

    Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3' terminal promoter region in the viral minus-strand (-)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5' proximal RIII(-) replication enhancer (REN) element in the TBSV (-)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (-)RNA could unwind the dsRNA structure within the RIII(-) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(-) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(-) REN that promotes bringing the 5' and 3' terminal (-)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.

  12. Full trans-activation mediated by the immediate-early protein of equine herpesvirus 1 requires a consensus TATA box, but not its cognate binding sequence.

    Science.gov (United States)

    Kim, Seong K; Shakya, Akhalesh K; O'Callaghan, Dennis J

    2016-01-04

    The immediate-early protein (IEP) of equine herpesvirus 1 (EHV-1) has extensive homology to the IEP of alphaherpesviruses and possesses domains essential for trans-activation, including an acidic trans-activation domain (TAD) and binding domains for DNA, TFIIB, and TBP. Our data showed that the IEP directly interacted with transcription factor TFIIA, which is known to stabilize the binding of TBP and TFIID to the TATA box of core promoters. When the TATA box of the EICP0 promoter was mutated to a nonfunctional TATA box, IEP-mediated trans-activation was reduced from 22-fold to 7-fold. The IEP trans-activated the viral promoters in a TATA motif-dependent manner. Our previous data showed that the IEP is able to repress its own promoter when the IEP-binding sequence (IEBS) is located within 26-bp from the TATA box. When the IEBS was located at 100 bp upstream of the TATA box, IEP-mediated trans-activation was very similar to that of the minimal IE(nt -89 to +73) promoter lacking the IEBS. As the distance from the IEBS to the TATA box decreased, IEP-mediated trans-activation progressively decreased, indicating that the IEBS located within 100 bp from the TATA box sequence functions as a distance-dependent repressive element. These results indicated that IEP-mediated full trans-activation requires a consensus TATA box of core promoters, but not its binding to the cognate sequence (IEBS). Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Phenobarbital-dependent protein binding to Barbie box-like sequences in the coding region of cytochrome P450BM-3 gene from Bacillus megaterium.

    Science.gov (United States)

    Gaidamakova, E K; Alpatov, O V; Ischenko, I V; Kovalenko, S P; Lyakhovich, V V

    1996-12-12

    Phenobarbital-dependent protein binding was shown to occur to DNA fragments from the coding region of the cytochrome P450BM-3 gene from Bacillus megaterium. Incubation of the DNA fragments from the coding region of the gene with total cell extract from Bacillus megaterium revealed two DNA regions with protein-binding capacity: +237/+318 and +319/+425 considering 'O' as the start of cytochrome P450BM-3 translation. DNaseI footprint analysis of the fragment +319/+425 with the total cell extract showed that some protein(s) protected DNA stretches from the position +373 up to the position +389 on the transcribed strand and from the position +378 up to the position +398 on the non-transcribed strand. DNaseI footprint analysis of the fragment +237/+318 revealed the protection in the region +262/+277 on the non-transcribed strand. Three regions protected by cell extract protein(s) from DNaseI hydrolysis (+262/+277, +373/+389 and +378/+398) appeared to be strongly homologous to the Barbie box sequence. Barbie-box-like sequences were found in the majority of regulatory regions of phenobarbital-inducible genes whose regulatory sequences had been reported (Fulco et al., 1994). Our results suggest that a functional role of Barbie box sequence takes place not only in regulatory but also in the coding region of the gene. In line with that hypothesis we analyzed all cytochrome P450 genes in respect to the presence of Barbie box-like sequences in their coding parts. At least one cytochrome P450 gene (CYP6A1, phenobarbital-inducible gene from Musca domestica) was shown to contain Barbie box sequence in the coding part of the gene.

  14. Protein Interaction Screening for the Ankyrin Repeats and Suppressor of Cytokine Signaling (SOCS) Box (ASB) Family Identify Asb11 as a Novel Endoplasmic Reticulum Resident Ubiquitin Ligase

    DEFF Research Database (Denmark)

    Andresen, Christina Aaen; Smedegaard, Stine; Sylvestersen, Kathrine Beck

    2014-01-01

    The Ankyrin and SOCS (Suppressor of Cytokine Signaling) box (ASB) family of proteins function as the substrate recognition subunit in a subset of Elongin-Cullin-SOCS (ECS) E3 ubiquitin ligases. Despite counting with 18 members in humans, the identity of the physiological targets of the Asb protei...

  15. The Y-Box Binding Protein 1 Suppresses Alzheimer’s Disease Progression in Two Animal Models

    Science.gov (United States)

    Bobkova, N. V.; Lyabin, D. N.; Medvinskaya, N. I.; Samokhin, A. N.; Nekrasov, P. V.; Nesterova, I. V.; Aleksandrova, I. Y.; Tatarnikova, O. G.; Bobylev, A. G.; Vikhlyantsev, I. M.; Kukharsky, M. S.; Ustyugov, A. A.; Polyakov, D. N.; Eliseeva, I. A.; Kretov, D. A.; Guryanov, S. G.; Ovchinnikov, L. P.

    2015-01-01

    The Y-box binding protein 1 (YB-1) is a member of the family of DNA- and RNA binding proteins. It is involved in a wide variety of DNA/RNA-dependent events including cell proliferation and differentiation, stress response, and malignant cell transformation. Previously, YB-1 was detected in neurons of the neocortex and hippocampus, but its precise role in the brain remains undefined. Here we show that subchronic intranasal injections of recombinant YB-1, as well as its fragment YB-11−219, suppress impairment of spatial memory in olfactory bulbectomized (OBX) mice with Alzheimer’s type degeneration and improve learning in transgenic 5XFAD mice used as a model of cerebral amyloidosis. YB-1-treated OBX and 5XFAD mice showed a decreased level of brain β-amyloid. In OBX animals, an improved morphological state of neurons was revealed in the neocortex and hippocampus; in 5XFAD mice, a delay in amyloid plaque progression was observed. Intranasally administered YB-1 penetrated into the brain and could enter neurons. In vitro co-incubation of YB-1 with monomeric β-amyloid (1–42) inhibited formation of β-amyloid fibrils, as confirmed by electron microscopy. This suggests that YB-1 interaction with β-amyloid prevents formation of filaments that are responsible for neurotoxicity and neuronal death. Our data are the first evidence for a potential therapeutic benefit of YB-1 for treatment of Alzheimer’s disease. PMID:26394155

  16. Integral membrane proteins in proteomics. How to break open the black box?

    Science.gov (United States)

    Vit, O; Petrak, J

    2017-02-05

    Integral membrane proteins (IMPs) are coded by 20-30% of human genes and execute important functions - transmembrane transport, signal transduction, cell-cell communication, cell adhesion to the extracellular matrix, and many other processes. Due to their hydrophobicity, low expression and lack of trypsin cleavage sites in their transmembrane segments, IMPs have been generally under-represented in routine proteomic analyses. However, the field of membrane proteomics has changed markedly in the past decade, namely due to the introduction of filter assisted sample preparation (FASP), the establishment of cell surface capture (CSC) protocols, and the development of methods that enable analysis of the hydrophobic transmembrane segments. This review will summarize the recent developments in the field and outline the most successful strategies for the analysis of integral membrane proteins. Integral membrane proteins (IMPs) are attractive therapeutic targets mostly due to their many important functions. However, our knowledge of the membrane proteome is severely limited to effectively exploit their potential. This is mostly due to the lack of appropriate techniques or methods compatible with the typical features of IMPs, namely hydrophobicity, low expression and lack of trypsin cleavage sites. This review summarizes the most recent development in membrane proteomics and outlines the most successful strategies for their large-scale analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Schistosoma mansoni: Heterologous complementation of a yeast null mutant by SmRbx, a protein similar to a RING box protein involved in ubiquitination.

    Science.gov (United States)

    Santos, Débora N; Aguiar, Pedro H N; Lobo, Francisco P; Mourão, Marina M; Tambor, José H M; Valadão, Analina F; Vilas-Boas, Adlane; Nobrega, Francisco G; LoVerde, Philip T; Macedo, Andréa M; Pena, Sérgio D J; Machado, Carlos R; Franco, Glória R

    2007-08-01

    The SCF (Skp1-Cul1-F-box) complex is one of the several E3 ligase enzymes and it catalyzes protein ubiquitination and degradation by the 26S proteasome. Rbx1 is a member of the SCF complex in humans and HRT1 is its yeast orthologue. A cDNA encoding a Schistosoma mansoni Rbx1 homolog was cloned and functionally characterized. Heterologous functional complementation in yeast showed that the worm SmRbx gene was able to complement the HRT1yeast null mutation. Gene deletion constructs for N- and C-termini truncated proteins were used to transform hrt1(-) yeast mutant strains, allowing us to observe that regions reported to be involved in the interaction with cullin1 (Cul1) were essential for SmRbx function. Yeast two-hybrid assays using SmRbx and yeast Cul1 confirmed that SmRbx, but not the mutant SmRbxDelta24N, lacking the N-terminus of the protein, was capable of interacting with Cul1. These results suggest that SmRbx protein is involved in the SCF complex formation.

  18. Circulating pathogen-associated molecular pattern - binding proteins and High Mobility Group Box protein 1 in nascent metabolic syndrome: implications for cellular Toll-like receptor activity.

    Science.gov (United States)

    Jialal, I; Rajamani, U; Adams-Huet, B; Kaur, H

    2014-09-01

    The Metabolic Syndrome, (MetS) a global epidemic, is a state of low grade chronic inflammation and confers an increased risk for diabetes and CVD. We have previously reported increased activity of the pathogen recognition receptors, Toll-like receptors (TLRs), TLR2 and TLR4 in MetS. We hypothesized that increased TLR activity in MetS is due in part to increased levels of circulating PAMP-binding proteins, soluble CD14 (sCD14), lipopolysaccharide binding protein (LBP) and the damage associated molecular pattern (DAMP), High Mobility Group Box protein 1 (HMGB-1). We measured sCD14, LBP and HMGB-1 in fasting plasma from nascent MetS (n = 37) and healthy control subjects (n = 32) by ELISA. We also investigated the effects of sCD14 and LBP on TLR4 activity in human aortic endothelial cells (HAECs). Following adjustment for body mass index and waist circumference, sCD14, LBP and HMGB-1 levels remained significantly increased in MetS. Also their levels increased with increasing numbers of MetS risk factors. Only sCD14 correlated significantly with monocyte TLR4 protein and activity. None of these soluble biomarkers correlated with TLR2 protein. Both sCD14 and HMGB-1 correlated significantly with HOMA-IR. In LPS primed HAECs, sCD14 compared to LBP, resulted in a greater increase in both TLR4 abundance and inflammatory biomediators (NF-κB, IL-1β, IL-8 and TNF-α). Thus, we make the novel observation that sCD14 reflects increased monocyte TLR4 protein and activity in nascent MetS and by contributing to increased cellular inflammation could explain, in part, the increased risk for diabetes and CVD. Published by Elsevier Ireland Ltd.

  19. Bento Boxes

    Science.gov (United States)

    Hasio, Cindy

    2010-01-01

    Bento boxes are common objects in Japanese culture, designed to hold enough lunch for one person. They have individual compartments and sometimes multiple tiers for rice, vegetables, and other side dishes. They are made of materials ranging from wood, cloth, aluminum, or plastic. In general, the greater the number of foods, the better the box is…

  20. The F-box-containing protein UFO and AGAMOUS participate in antagonistic pathways governing early petal development in Arabidopsis.

    Science.gov (United States)

    Durfee, Tim; Roe, Judith L; Sessions, R Allen; Inouye, Carla; Serikawa, Kyle; Feldmann, Kenneth A; Weigel, Detlef; Zambryski, Patricia C

    2003-07-08

    The UNUSUAL FLORAL ORGANS (UFO) gene is required for multiple processes in the developing Arabidopsis flower, including the proper patterning and identity of both petals and stamens. The gene encodes an F-box-containing protein, UFO, which interacts physically and genetically with the Skp1 homolog, ASK1. In this report, we describe four ufo alleles characterized by the absence of petals, which uncover another role for UFO in promoting second whorl development. This UFO-dependent pathway is required regardless of the second whorl organ to be formed, arguing that it affects a basic process acting in parallel with those establishing organ identity. However, the pathway is dispensable in the absence of AGAMOUS (AG), a known inhibitor of petal development. In situ hybridization results argue that AG is not transcribed in the petal region, suggesting that it acts non-cell-autonomously to inhibit second whorl development in ufo mutants. These results are combined into a genetic model explaining early second whorl initiation/proliferation, in which UFO functions to inhibit an AG-dependent activity.

  1. Cellular localization of Y-box binding protein 1 in brain tissue of rats, macaques, and humans

    Directory of Open Access Journals (Sweden)

    Horn Anja

    2009-03-01

    Full Text Available Abstract Background The Y-box binding protein 1 (YB-1 is considered to be one of the key regulators of transcription and translation. However, so far only limited knowledge exists regarding its cellular distribution in the adult brain. Results Analysis of YB-1 immunolabelling as well as double-labelling with the neuronal marker NeuN in rat brain tissue revealed a predominant neuronal expression in the dentate gyrus, the cornu ammonis pyramidal cell layer, layer III of the piriform cortex as well as throughout all layers of the parahippocampal cortex. In the hilus of the hippocampus single neurons expressed YB-1. The neuronal expression pattern was comparable in the hippocampus and parahippocampal cortex of adult macaques and humans. Double-labelling of YB-1 with the endothelial cell marker Glut-1, the multidrug transporter P-glycoprotein, and the astrocytic marker GFAP did not indicate a co-localization. Following status epilepticus in rats, no induction of YB-1 occurred in brain capillary endothelial cells and neurons. Conclusion In conclusion, our study demonstrates that YB-1 is predominantly expressed in neurons in the adult brain of rats, macaques and humans. Lack of a co-localization with Glut-1 and P-glycoprotein argues against a direct role of YB-1 in the regulation of blood-brain barrier P-glycoprotein.

  2. Increased expression of high mobility group box protein 1 and vascular endothelial growth factor in placenta previa.

    Science.gov (United States)

    Xie, Han; Qiao, Ping; Lu, Yi; Li, Ying; Tang, Yuping; Huang, Yiying; Bao, Yirong; Ying, Hao

    2017-12-01

    Placenta previa is often associated with preterm delivery, reduced birth weight, a higher frequency of placental accreta and postpartum haemorrhage, and increased likelihood of blood transfusion. The present study aimed to examine the expression of high mobility group box protein 1 (HMGB1) in the placenta of women with or without placenta previa. The study group consisted of placental tissues obtained from women with or without placenta previa. The expression levels of HMGB1 and vascular endothelial growth factor (VEGF) were evaluated in the placental tissues using reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemistry. The mRNA expression levels of HMGB1 and VEGF were significantly increased in the placenta previa group compared with in the normal group. In addition, the placenta previa group exhibited increased HMGB1 and VEGF staining in vascular endothelial cells and trophoblasts. There were no significant differences in the expression of HMGB1 or VEGF between groups with or without placenta accreta or postpartum haemorrhage. The present study hypothesised that the increased expression of HMGB1 in the placenta may be associated with the pathogenesis of placenta previa by regulating the expression of the proangiogenic factor VEGF.

  3. WsMAGO2, a duplicated MAGO NASHI protein with fertility attributes interacts with MPF2-like MADS-box proteins.

    Science.gov (United States)

    Ihsan, Humera; Khan, Muhammad Ramzan; Ajmal, Wajya; Ali, Ghulam Muhammad

    2015-05-01

    WsMAGO2 a duplicated protein in Withania through interactions with MPF2-like proteins affects male fertility by producing fewer flowers and aborted non-viable pollens/seeds regulated by anther-specific GAATTTGTGA motif. The MAGO NASHIs are highly conserved genes that encode proteins known to be involved in RNA physiology and many other developmental processes including germ cell differentiation in animals. However, their structural and functional implications in plants as fertility function proteins remained fragmented. MAGO (shorter name of MAGO NASHI) proteins form heterodimers with MPF2-like MADS-box proteins which are recruited in calyx identity and male fertility in Solanaceous plants. Four MAGO genes namely WsMAGO1 and WsMAGO2 and TaMAGO1 and TaMAGO2 were isolated from Withania somnifera and Tubocapsicum anomalum, respectively. These genes have duplicated probably due to whole genome duplication event. Dysfunction of WsMAGO2 through double-stranded RNAi in Withania revealed suppression of RNA transcripts, non-viable pollens, fewer flowers and aborted non-viable seeds in the developing berry suggesting a role of this protein in many traits particularly male fertility. WsMAGO2 flaunted stronger yeast 2-hybrid interactions with MPF2-like proteins WSA206, WSB206 and TAB201 than other MAGO counterparts. The native transcripts of WsMAGO2 culminated in stamens and seed-bearing berries though other MAGO orthologs also exhibited expression albeit at lower level. Coding sequences of the two orthologs are highly conserved, but they differ substantially in their upstream promoter regions. Remarkably, WsMAGO2 promoter is enriched with many anther-specific cis-motifs common in fertility function genes promoters. Among them, disruption of GAATTTGTGA abolished YFP/GUS gene expression in anthers alluding towards its involvement in regulating expression of MAGO in anther. Our findings support a possible recruitment of WsMAGO2 in fertility trait in Withania. These genes have

  4. Characterization of novel roles of a HMG-box protein PoxHmbB in biomass-degrading enzyme production by Penicillium oxalicum.

    Science.gov (United States)

    Xiong, Ya-Ru; Zhao, Shuai; Fu, Li-Hao; Liao, Xu-Zhong; Li, Cheng-Xi; Yan, Yu-Si; Liao, Lu-Sheng; Feng, Jia-Xun

    2018-04-01

    High-mobility group (HMG)-box proteins are involved in chromatin organization in eukaryotes, especially in sex determination and regulation of mitochondrial DNA compaction. Although a novel HMG-box protein, PoxHmbB, had been initially identified to be required for filter paper cellulase activity by Penicillium oxalicum, the biological roles of HMG-box proteins in biomass-degrading enzyme production have not been systematically explored. The P. oxalicum mutant ∆PoxHmbB lost 34.7-86.5% of cellulase (endoglucanase, p-nitrophenyl-β-cellobiosidase, and p-nitrophenyl-β-glucopyranosidase) activities and 60.3% of xylanase activity following Avicel induction, whereas it exhibited about onefold increase in amylase activity following soluble corn starch induction. Furthermore, ∆PoxHmbB presented delayed conidiation and hyphae growth. Transcriptomic profiling and real-time quantitative reverse transcription-PCR revealed that PoxHmbB regulated the expression of major genes encoding plant biomass-degrading enzymes such as PoxCel7A-2, PoxCel5B, PoxBgl3A, PoxXyn11B, and PoxGA15A, as well as those involved in conidiation such as PoxBrlA. In vitro binding experiments further confirmed that PoxHmbB directly binds to the promoter regions of these major genes. These results further indicate the diversity of the biological functions of HMG-box proteins and provide a novel and promising engineering target for improving plant biomass-degrading enzyme production in filamentous fungi.

  5. Non–SCF-type F-box protein Roy1/Ymr258c interacts with a Rab5-like GTPase Ypt52 and inhibits Ypt52 function

    Science.gov (United States)

    Liu, Yuan; Nakatsukasa, Kunio; Kotera, Michiko; Kanada, Akira; Nishimura, Takashi; Kishi, Tsutomu; Mimura, Satoru; Kamura, Takumi

    2011-01-01

    Skp1/Cul1/F-box (SCF)–type F-box proteins are a component of the Cullin-RING SCF ubiquitin E3 ligase, which is involved in numerous cellular processes. However, the function of non–SCF-type F-box proteins remains largely unknown. The Rab5-like small guanosine 5′-triphosphatase Vps21/Ypt51 is a key regulator of intracellular transportation; however, deletion of its isoforms, Ypt52 and Ypt53, results in only a modest inhibition of intracellular trafficking. The function of these proteins therefore remains largely elusive. Here we analyze the role of a previously uncharacterized non–SCF-type F-box protein, Roy1/Ymr258c, in cell growth and intracellular transport in Saccharomyces cerevisiae. Roy1 binds to Ypt52 under physiological conditions, and Skp1 is indispensable for the association of Roy1 with Ypt52. The vps21Δ yeast cells exhibit severe deficiencies in cell growth and intracellular trafficking, whereas simultaneous deletion of roy1 alleviates the defects caused by deletion of vps21. However, additional disruption of ypt52 in roy1Δvps21Δ cells largely suppresses the cell growth and trafficking observed in roy1Δvps21Δ cells. We demonstrate that Roy1 interacts with guanosine 5′-diphosphate–bound and nucleotide-free Ypt52 and thereby inhibits the formation of guanosine 5′-triphosphate–bound, active Ypt52. These results thus indicate that Roy1 negatively modulates cell viability and intracellular transport by suppressing Ypt52. PMID:21389113

  6. Non-SCF-type F-box protein Roy1/Ymr258c interacts with a Rab5-like GTPase Ypt52 and inhibits Ypt52 function.

    Science.gov (United States)

    Liu, Yuan; Nakatsukasa, Kunio; Kotera, Michiko; Kanada, Akira; Nishimura, Takashi; Kishi, Tsutomu; Mimura, Satoru; Kamura, Takumi

    2011-05-01

    Skp1/Cul1/F-box (SCF)-type F-box proteins are a component of the Cullin-RING SCF ubiquitin E3 ligase, which is involved in numerous cellular processes. However, the function of non-SCF-type F-box proteins remains largely unknown. The Rab5-like small guanosine 5'-triphosphatase Vps21/Ypt51 is a key regulator of intracellular transportation; however, deletion of its isoforms, Ypt52 and Ypt53, results in only a modest inhibition of intracellular trafficking. The function of these proteins therefore remains largely elusive. Here we analyze the role of a previously uncharacterized non-SCF-type F-box protein, Roy1/Ymr258c, in cell growth and intracellular transport in Saccharomyces cerevisiae. Roy1 binds to Ypt52 under physiological conditions, and Skp1 is indispensable for the association of Roy1 with Ypt52. The vps21Δ yeast cells exhibit severe deficiencies in cell growth and intracellular trafficking, whereas simultaneous deletion of roy1 alleviates the defects caused by deletion of vps21. However, additional disruption of ypt52 in roy1Δvps21Δ cells largely suppresses the cell growth and trafficking observed in roy1Δvps21Δ cells. We demonstrate that Roy1 interacts with guanosine 5'-diphosphate-bound and nucleotide-free Ypt52 and thereby inhibits the formation of guanosine 5'-triphosphate-bound, active Ypt52. These results thus indicate that Roy1 negatively modulates cell viability and intracellular transport by suppressing Ypt52.

  7. Markedly Increased High-Mobility Group Box 1 Protein in a Patient with Small-for-Size Syndrome

    Directory of Open Access Journals (Sweden)

    Darren G. Craig

    2014-01-01

    Full Text Available Background. Small-for-size syndrome (SFSS occurs in the presence of insufficient liver mass to maintain normal function after liver transplantation. Murine mortality following 85% hepatectomy can be reduced by the use of soluble receptor for advanced glycation end products (sRAGE to scavenge damage-associated molecular patterns and prevent their engagement with membrane-bound RAGE. Aims. To explore serum levels of sRAGE, high-mobility group box-1 (HMGB1 protein, and other soluble inflammatory mediators in a fatal case of SFSS. Methods. Serum levels of HMGB1, sRAGE, IL-18, and other inflammatory mediators were measured by ELISA in a case of SFSS, and the results were compared with 8 patients with paracetamol-induced acute liver failure (ALF and 6 healthy controls (HC. Results. HMGB1 levels were markedly higher in the SFSS patient (92.1 ng/mL compared with the ALF patients (median (IQR 11.4 (3.7–14.8 ng/mL and HC (1.42 (1.38–1.56 ng/mL. In contrast, sRAGE levels were lower in the SFSS patient (1.88 ng/mL compared with the ALF patients (3.53 (2.66–12.37 ng/mL and were similar to HC levels (1.40 (1.23–1.89 ng/mL. Conclusion. These results suggest an imbalance between pro- and anti-inflammatory innate immune pathways in SFSS. Modulation of the HMGB1-RAGE axis may represent a future therapeutic avenue in this condition.

  8. Autoantibodies to box A of high mobility group box 1 in systemic lupus erythematosus

    NARCIS (Netherlands)

    Schaper, F.; de Leeuw, K.; Horst, G.; Maas, F.; Bootsma, H.; Heeringa, P.; Limburg, P. C.; Westra, J.

    Autoantibodies to nuclear structures are a hallmark of systemic lupus erythematosus (SLE), including autoantibodies to nuclear protein high mobility group box 1 (HMGB1). HMGB1 consists of three separate domains: box A, box B and an acidic tail. Recombinant box A acts as a competitive antagonist for

  9. Autoantibodies to box A of high mobility group box 1 in systemic lupus erythematosus

    NARCIS (Netherlands)

    Schaper, F.; Leeuw, K. de; Horst, G. ter; Maas, F.; Bootsma, H.; Heeringa, P.; Limburg, P.C.; Westra, J.

    2017-01-01

    Autoantibodies to nuclear structures are a hallmark of systemic lupus erythematosus (SLE), including autoantibodies to nuclear protein high mobility group box 1 (HMGB1). HMGB1 consists of three separate domains: box A, box B and an acidic tail. Recombinant box A acts as a competitive antagonist for

  10. [Effects of exogenous high mobility group protein box 1 on angiogenesis in ischemic zone of early scald wounds of rats].

    Science.gov (United States)

    Dai, L; Guo, X; Huang, H J; Liao, X M; Luo, X Q; Li, D; Zhou, H; Gao, X C; Tan, M Y

    2018-04-20

    Objective: To observe effects of exogenous high mobility group protein box 1 (HMGB1) on angiogenesis in ischemic zone of early scald wounds of rats. Methods: Thirty-six Sprague-Dawley rats were divided into HMGB1 group and simple scald (SS) group according to the random number table, with 18 rats in each group. Comb-like copper mould was placed on the back of rats for 20 s after being immersed in 100 ℃ hot water for 3 to 5 min to make three ischemic zones of wound. Immediately after scald, rats in HMGB1 group were subcutaneously injected with 0.4 μg HMGB1 and 0.1 mL phosphate buffer solution (PBS), and rats in SS group were subcutaneously injected with 0.1 mL PBS from boarders of ischemic zone of scald wound. At post scald hour (PSH) 24, 48, and 72, 6 rats in each group were collected. Protein expressions of vascular endothelial growth factor (VEGF) in ischemic zone of wound at PSH 24, 48, and 72 and protein expressions of CD31 in ischemic zone of wound at PSH 48 and 72 were detected by immunohistochemistry. The number of microvessel in CD31 immunohistochemical sections of ischemic zone of wound at PSH 48 and 72 was calculated after observing by the microscope. The mRNA expressions of VEGF and CD31 in ischemic zone of wound were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction at PSH 24, 48, and 72. Data were processed with analysis of variance of factorial design, t test, and Bonferroni correction. Results: (1) At PSH 24, 48, and 72, protein expressions of VEGF in ischemic zone of wound of rats in HMGB1 group were significantly higher than those of rats in SS group ( t =7.496, 4.437, 5.402, P zone of wound of rats in HMGB1 group were 0.038 8±0.007 9 and 0.057 7±0.001 2 respectively, significantly higher than 0.013 4±0.004 9 and 0.030 3±0.004 0 of rats in SS group ( t =10.257, 15.055, P zone of wound of rats in HMGB1 group was obviously more than that of rats in SS group ( t =3.536, 4.000, P zone of wound of

  11. Banana Ovate family protein MaOFP1 and MADS-box protein MuMADS1 antagonistically regulated banana fruit ripening.

    Directory of Open Access Journals (Sweden)

    Juhua Liu

    Full Text Available The ovate family protein named MaOFP1 was identified in banana (Musa acuminata L.AAA fruit by a yeast two-hybrid (Y2H method using the banana MADS-box gene MuMADS1 as bait and a 2 day postharvest (DPH banana fruit cDNA library as prey. The interaction between MuMADS1 and MaOFP1 was further confirmed by Y2H and Bimolecular Fluorescence Complementation (BiFC methods, which showed that the MuMADS1 K domain interacted with MaOFP1. Real-time quantitative PCR evaluation of MuMADS1 and MaOFP1 expression patterns in banana showed that they are highly expressed in 0 DPH fruit, but present in low levels in the stem, which suggests that simultaneous but different expression patterns exist for both MuMADS1 and MaOFP1 in different tissues and developing fruits. Meanwhile, MuMADS1 and MaOFP1 expression was highly stimulated and greatly suppressed, respectively, by exogenous ethylene. In contrast, MaOFP1 expression was highly stimulated while MuMADS1 was greatly suppressed by the ethylene competitor 1-methylcyclopropene (1-MCP. These results indicate that MuMADS1 and MaOFP1 are antagonistically regulated by ethylene and might play important roles in postharvest banana fruit ripening.

  12. The dengue vector Aedes aegypti contains a functional high mobility group box 1 (HMGB1) protein with a unique regulatory C-terminus.

    Science.gov (United States)

    Ribeiro, Fabio Schneider; de Abreu da Silva, Isabel Caetano; Carneiro, Vitor Coutinho; Belgrano, Fabrício dos Santos; Mohana-Borges, Ronaldo; de Andrade Rosa, Ivone; Benchimol, Marlene; Souza, Nathalia Rocha Quintino; Mesquita, Rafael Dias; Sorgine, Marcos Henrique Ferreira; Gazos-Lopes, Felipe; Vicentino, Amanda Roberta Revoredo; Wu, Wenjie; de Moraes Maciel, Renata; da Silva-Neto, Mario Alberto Cardoso; Fantappié, Marcelo Rosado

    2012-01-01

    The mosquito Aedes aegypti can spread the dengue, chikungunya and yellow fever viruses. Thus, the search for key molecules involved in the mosquito survival represents today a promising vector control strategy. High Mobility Group Box (HMGB) proteins are essential nuclear factors that maintain the high-order structure of chromatin, keeping eukaryotic cells viable. Outside the nucleus, secreted HMGB proteins could alert the innate immune system to foreign antigens and trigger the initiation of host defenses. In this work, we cloned and functionally characterized the HMGB1 protein from Aedes aegypti (AaHMGB1). The AaHMGB1 protein typically consists of two HMG-box DNA binding domains and an acidic C-terminus. Interestingly, AaHMGB1 contains a unique alanine/glutamine-rich (AQ-rich) C-terminal region that seems to be exclusive of dipteran HMGB proteins. AaHMGB1 is localized to the cell nucleus, mainly associated with heterochromatin. Circular dichroism analyses of AaHMGB1 or the C-terminal truncated proteins revealed α-helical structures. We showed that AaHMGB1 can effectively bind and change the topology of DNA, and that the AQ-rich and the C-terminal acidic regions can modulate its ability to promote DNA supercoiling, as well as its preference to bind supercoiled DNA. AaHMGB1 is phosphorylated by PKA and PKC, but not by CK2. Importantly, phosphorylation of AaHMGB1 by PKA or PKC completely abolishes its DNA bending activity. Thus, our study shows that a functional HMGB1 protein occurs in Aedes aegypt and we provide the first description of a HMGB1 protein containing an AQ-rich regulatory C-terminus.

  13. The dengue vector Aedes aegypti contains a functional high mobility group box 1 (HMGB1 protein with a unique regulatory C-terminus.

    Directory of Open Access Journals (Sweden)

    Fabio Schneider Ribeiro

    Full Text Available The mosquito Aedes aegypti can spread the dengue, chikungunya and yellow fever viruses. Thus, the search for key molecules involved in the mosquito survival represents today a promising vector control strategy. High Mobility Group Box (HMGB proteins are essential nuclear factors that maintain the high-order structure of chromatin, keeping eukaryotic cells viable. Outside the nucleus, secreted HMGB proteins could alert the innate immune system to foreign antigens and trigger the initiation of host defenses. In this work, we cloned and functionally characterized the HMGB1 protein from Aedes aegypti (AaHMGB1. The AaHMGB1 protein typically consists of two HMG-box DNA binding domains and an acidic C-terminus. Interestingly, AaHMGB1 contains a unique alanine/glutamine-rich (AQ-rich C-terminal region that seems to be exclusive of dipteran HMGB proteins. AaHMGB1 is localized to the cell nucleus, mainly associated with heterochromatin. Circular dichroism analyses of AaHMGB1 or the C-terminal truncated proteins revealed α-helical structures. We showed that AaHMGB1 can effectively bind and change the topology of DNA, and that the AQ-rich and the C-terminal acidic regions can modulate its ability to promote DNA supercoiling, as well as its preference to bind supercoiled DNA. AaHMGB1 is phosphorylated by PKA and PKC, but not by CK2. Importantly, phosphorylation of AaHMGB1 by PKA or PKC completely abolishes its DNA bending activity. Thus, our study shows that a functional HMGB1 protein occurs in Aedes aegypt and we provide the first description of a HMGB1 protein containing an AQ-rich regulatory C-terminus.

  14. Ankyrin repeat and SOCS box containing protein 4 (Asb-4 colocalizes with insulin receptor substrate 4 (IRS4 in the hypothalamic neurons and mediates IRS4 degradation

    Directory of Open Access Journals (Sweden)

    Xia Zefeng

    2011-09-01

    Full Text Available Abstract Background The arcuate nucleus of the hypothalamus regulates food intake. Ankyrin repeat and SOCS box containing protein 4 (Asb-4 is expressed in neuropeptide Y and proopiomelanocortin (POMC neurons in the arcuate nucleus, target neurons in the regulation of food intake and metabolism by insulin and leptin. However, the target protein(s of Asb-4 in these neurons remains unknown. Insulin receptor substrate 4 (IRS4 is an adaptor molecule involved in the signal transduction by both insulin and leptin. In the present study we examined the colocalization and interaction of Asb-4 with IRS4 and the involvement of Asb-4 in insulin signaling. Results In situ hybridization showed that the expression pattern of Asb-4 was consistent with that of IRS4 in the rat brain. Double in situ hybridization showed that IRS4 colocalized with Asb-4, and both Asb-4 and IRS4 mRNA were expressed in proopiomelanocortin (POMC and neuropeptide Y (NPY neurons within the arcuate nucleus of the hypothalamus. In HEK293 cells co-transfected with Myc-tagged Asb-4 and Flag-tagged IRS4, Asb-4 co-immunoprecipitated with IRS4; In these cells endogenous IRS4 also co-immunoprecipitated with transfected Myc-Asb-4; Furthermore, Asb-4 co-immunoprecipitated with IRS4 in rat hypothalamic extracts. In HEK293 cells over expression of Asb-4 decreased IRS4 protein levels and deletion of the SOCS box abolished this effect. Asb-4 increased the ubiquitination of IRS4; Deletion of SOCS box abolished this effect. Expression of Asb-4 decreased both basal and insulin-stimulated phosphorylation of AKT at Thr308. Conclusions These data demonstrated that Asb-4 co-localizes and interacts with IRS4 in hypothalamic neurons. The interaction of Asb-4 with IRS4 in cell lines mediates the degradation of IRS4 and decreases insulin signaling.

  15. Simulating detectors dead time

    International Nuclear Information System (INIS)

    Rustom, Ibrahim Farog Ibrahim

    2015-06-01

    Nuclear detectors are used in all aspects of nuclear measurements. All nuclear detectors are characterized by their dead time i.e. the time needed by a detector to recover from a previous incident. A detector dead time influences measurements taken by a detector and specially when measuring high decay rate (>) where is the detector dead time. Two models are usually used to correct for the dead time effect: the paralayzable and the non-paralayzable models. In the current work we use Monte Carlo simulation techniques to simulate radioactivity and the effect of dead time and the count rate of a detector with a dead time =5x10 - 5s assuming the non-paralayzable model. The simulation indicates that assuming a non -paralayzable model could be used to correct for decay rate measured by a detector. The reliability of the non-paralayzable model to correct the measured decay rate could be gauged using the Monte Carlo simulation. (Author)

  16. Glove box

    International Nuclear Information System (INIS)

    Morita, Atsushi

    1990-01-01

    Wire rope earthquake proof supports having sufficient vibration transmitting and attenuating property are disposed between a fixed floor and the bottom of a glove box in order to improve earthquake proofness of the glove box. The vertical weight of the glove box is supported by support legs slidable on the surface of the fixed floor. The wire rope earthquake-proof supports when undergoing a load, cause stretching and rolling against the external force such as earthquakes, and provide flexible spring support and cause a great damping due to friction with strands. Further, the vertical weight is always supported by the support legs and, when a horizontal weight is applied, the glove box slides on the fixed floor freely with slidable members. In this way, stress concentration generated at joint portions of columns and beams can be moderated greatly and earthquake proofness can be improved. Further, quality control and maintenance for the device is almost unnecessary owing to excellent fatigue-resistant characteristics of the wire rope earthquake proof supports. (N.H.)

  17. Contribution of phenylalanine side chain intercalation to the TATA-box binding protein-DNA interaction: molecular dynamics and dispersion-corrected density functional theory studies.

    Science.gov (United States)

    Mondal, Manas; Mukherjee, Sanchita; Bhattacharyya, Dhananjay

    2014-11-01

    Deformation of DNA takes place quite often due to binding of small molecules or proteins with DNA. Such deformation is significant due to minor groove binding and, besides electrostatic interactions, other non-covalent interactions may also play an important role in generating such deformation. TATA-box binding protein (TBP) binds to the minor groove of DNA at the TATA box sequence, producing a large-scale deformation in DNA and initiating transcription. In order to observe the interactions of protein residues with DNA in the minor groove that produce the deformation in the DNA structure, we carried out molecular dynamics simulations of the TBP-DNA system. The results reveal consistent partial intercalation of two Phe residues, distorting stacking interactions at two dinucleotide step sites. We carried out calculations based on dispersion-corrected density functional theory to understand the source of such stabilization. We observed favorable interaction energies between the Phe residues and the base pairs with which they interact. We suggest that salt-bridge interactions between the phosphate groups and Lys or Arg residues, along with the intercalation of Phe residues between two base pair stacks, stabilize the kinked and opened-up DNA conformation.

  18. Glove boxes

    International Nuclear Information System (INIS)

    Eisert, G.A.

    1979-01-01

    An arrangement for effecting access for performing work within a glove box comprises an elongate arm-length impermeable flexible sleeve, a fitting having an aperture therethrough, adapted to be secured in sealing relation in a port, in a wall of the glove box, the fitting including an outwardly extending lip having at least one continuous groove extending around its outer periphery, one end of the sleeve extending through the aperture in fitting and being folded back against the outer periphery of the lip, a resilient fastening ring securing the sleeve in sealing engagement in the groove, clamping means securing the sleeves to the lip and a glove secured in sealing relation via a bushing to the other end of the sleeve. (author)

  19. Investigating Aquatic Dead Zones

    Science.gov (United States)

    Testa, Jeremy; Gurbisz, Cassie; Murray, Laura; Gray, William; Bosch, Jennifer; Burrell, Chris; Kemp, Michael

    2010-01-01

    This article features two engaging high school activities that include current scientific information, data, and authentic case studies. The activities address the physical, biological, and chemical processes that are associated with oxygen-depleted areas, or "dead zones," in aquatic systems. Students can explore these dead zones through both…

  20. STH2 has 2 B there: An insight into the role of B-box containing proteins in Arabidopsis

    OpenAIRE

    Datta, Sourav; Johansson, Henrik; Hettiarachchi, Chamari; Holm, Magnus

    2008-01-01

    Recently we reported the identification of a novel B-box transcription factor SALT TOLERANCE HOMOLOG 2 (STH2) that interacts genetically with two key regulators of the light-signaling pathway, HY5 and COP1.1 We also provided phenotypic and genetic characterization of the sth2 mutant suggesting that STH2 plays a positive role in regulating photomorphogenesis both independently or together with HY5. Functional assays in protoplasts revealed that STH2 could act as a transcriptional activator. To...

  1. Dead Sea Scrolls

    Science.gov (United States)

    1994-01-01

    A consortium of researchers from Jet Propulsion Laboratory and three other organizations used charged coupled devices (CCDs) and other imaging enhancement technology to decipher previously unreadable portions of the Dead Sea Scrolls. The technique has potentially important implications for archeology.

  2. The F-box Protein KIB1 Mediates Brassinosteroid-Induced Inactivation and Degradation of GSK3-like Kinases in Arabidopsis.

    Science.gov (United States)

    Zhu, Jia-Ying; Li, Yuyao; Cao, Dong-Mei; Yang, Hongjuan; Oh, Eunkyoo; Bi, Yang; Zhu, Shengwei; Wang, Zhi-Yong

    2017-06-01

    The glycogen synthase kinase-3 (GSK3) family kinases are central cellular regulators highly conserved in all eukaryotes. In Arabidopsis, the GSK3-like kinase BIN2 phosphorylates a range of proteins to control broad developmental processes, and BIN2 is degraded through unknown mechanism upon receptor kinase-mediated brassinosteroid (BR) signaling. Here we identify KIB1 as an F-box E3 ubiquitin ligase that promotes the degradation of BIN2 while blocking its substrate access. Loss-of-function mutations of KIB1 and its homologs abolished BR-induced BIN2 degradation and caused severe BR-insensitive phenotypes. KIB1 directly interacted with BIN2 in a BR-dependent manner and promoted BIN2 ubiquitination in vitro. Expression of an F-box-truncated KIB1 caused BIN2 accumulation but dephosphorylation of its substrate BZR1 and activation of BR responses because KIB1 blocked BIN2 binding to BZR1. Our study demonstrates that KIB1 plays an essential role in BR signaling by inhibiting BIN2 through dual mechanisms of blocking substrate access and promoting degradation. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Cell differentiation by interaction of two HMG-box proteins: Mat1-Mc activates M cell-specific genes in S.pombe by recruiting the ubiquitous transcription factor Ste11 to weak binding sites

    DEFF Research Database (Denmark)

    Kjaerulff, S; Dooijes, D; Clevers, H

    1997-01-01

    The Schizosaccharomyces pombe mfm1 gene is expressed in an M cell-specific fashion. This regulation requires two HMG-box proteins: the ubiquitous Ste11 transcription factor and the M cell-controlling protein Mat1-Mc. Here we report that the mfm1 promoter contains a single, weak Stell-binding site...... of a complex containing both Ste11 and Mat1-Mc. A single copy of this fragment was sufficient to activate a heterologous promoter in an M-specific fashion, suggesting that these two boxes act in a synergistic manner....

  4. Differential utilization of TATA box-binding protein (TBP) and TBP-related factor 1 (TRF1) at different classes of RNA polymerase III promoters.

    Science.gov (United States)

    Verma, Neha; Hung, Ko-Hsuan; Kang, Jin Joo; Barakat, Nermeen H; Stumph, William E

    2013-09-20

    In the fruit fly Drosophila melanogaster, RNA polymerase III transcription was found to be dependent not upon the canonical TATA box-binding protein (TBP) but instead upon the TBP-related factor 1 (TRF1) (Takada, S., Lis, J. T., Zhou, S., and Tjian, R. (2000) Cell 101, 459-469). Here we confirm that transcription of fly tRNA genes requires TRF1. However, we unexpectedly find that U6 snRNA gene promoters are occupied primarily by TBP in cells and that knockdown of TBP, but not TRF1, inhibits U6 transcription in cells. Moreover, U6 transcription in vitro effectively utilizes TBP, whereas TBP cannot substitute for TRF1 to promote tRNA transcription in vitro. Thus, in fruit flies, different classes of RNA polymerase III promoters differentially utilize TBP and TRF1 for the initiation of transcription.

  5. An apple B-box protein, MdCOL11, is involved in UV-B- and temperature-induced anthocyanin biosynthesis.

    Science.gov (United States)

    Bai, Songling; Saito, Takanori; Honda, Chikako; Hatsuyama, Yoshimichi; Ito, Akiko; Moriguchi, Takaya

    2014-11-01

    Our studies showed that an apple B-box protein, MdCOL11, the homolog of AtBBX22, is involved in UV-B- and temperature-induced anthocyanin biosynthesis in apple peel. Anthocyanin is responsible for the red pigmentation in apple peel and a R2R3 MYB gene, MdMYBA/1/10, a homolog of MdMYBA, controls its accumulation. Arabidopsis PAP1 is under the control of a series of upstream factors involved in light signal transduction and photomorphogenesis, such as ELONGATED HYPOCOTYL 5 (HY5) and B-box family (BBX) proteins. In this study, we identified and characterized the homolog of Arabidopsis BBX22 in apple, designated as MdCOL11. Overexpression of MdCOL11 in Arabidopsis enhanced the accumulation of anthocyanin. In apples, MdCOL11 was differentially expressed in all tissues, with the highest expression in petals and the lowest expression in the xylem. Transcripts of MdCOL11 noticeably accumulated at the ripening stage, concomitant with increases in the expressions of anthocyanin biosynthesis-related genes. In an in vitro treatment experiment, MdCOL11 was upregulated in an ultra-violet (UV)-B- and temperature-dependent manner, together with the inductions of anthocyanin biosynthesis-related genes and anthocyanin accumulation in apple peel. Furthermore, a dual-luciferase assay indicated that (1) MdCOL11 regulated the expression of MdMYBA and (2) MdCOL11 was a target of MdHY5. Taken together, our results suggest that MdCOL11 is involved in MdHY5-mediated signal transduction and regulates anthocyanin accumulation in apple peel, which sheds new light on anthocyanin accumulation in apples.

  6. Practicing on Newly Dead

    Directory of Open Access Journals (Sweden)

    Jewel Abraham

    2015-07-01

    Full Text Available A newly dead cadaver simulation is practiced on the physical remains of the dead before the onset of rigor mortis. This technique has potential benefits for providing real-life in-situ experience for novice providers in health care practices. Evolving ethical views in health care brings into question some of the ethical aspects associated with newly dead cadaver simulation in terms of justification for practice, autonomy, consent, and the need of disclosure. A clear statement of policies and procedures on newly dead cadaver simulation has yet to be implemented. Although there are benefits and disadvantages to an in-situ cadaver simulation, such practices should not be carried out in secrecy as there is no compelling evidence that suggests such training as imperative. Secrecy in these practices is a violation of honor code of nursing ethics. As health care providers, practitioners are obliged to be ethically honest and trustworthy to their patients. The author explores the ethical aspects of using newly dead cadaver simulation in training novice nursing providers to gain competency in various lifesaving skills, which otherwise cannot be practiced on a living individual. The author explores multiple views on cadaver simulation in relation to ethical theories and practices such as consent and disclosure to family.

  7. Elr-type proteins protect Xenopus Dead end mRNA from miR-18-mediated clearance in the soma

    OpenAIRE

    Koebernick, Katja; Loeber, Jana; Arthur, Patrick Kobina; Tarbashevich, Katsiaryna; Pieler, Tomas

    2010-01-01

    Segregation of the future germ line defines a crucial cell fate decision during animal development. In Xenopus, germ cells are specified by inheritance of vegetally localized maternal determinants, including a group of specific mRNAs. Here, we show that the vegetal localization elements (LE) of Xenopus Dead end (XDE) and of several other germ-line-specific, vegetally localized transcripts mediate germ cell-specific stabilization and somatic clearance of microinjected reporter mRNA in Xenopus ...

  8. A plant U-box protein, PUB4, regulates asymmetric cell division and cell proliferation in the root meristem.

    Science.gov (United States)

    Kinoshita, Atsuko; ten Hove, Colette A; Tabata, Ryo; Yamada, Masashi; Shimizu, Noriko; Ishida, Takashi; Yamaguchi, Katsushi; Shigenobu, Shuji; Takebayashi, Yumiko; Iuchi, Satoshi; Kobayashi, Masatomo; Kurata, Tetsuya; Wada, Takuji; Seo, Mitsunori; Hasebe, Mitsuyasu; Blilou, Ikram; Fukuda, Hiroo; Scheres, Ben; Heidstra, Renze; Kamiya, Yuji; Sawa, Shinichiro

    2015-02-01

    The root meristem (RM) is a fundamental structure that is responsible for postembryonic root growth. The RM contains the quiescent center (QC), stem cells and frequently dividing meristematic cells, in which the timing and the frequency of cell division are tightly regulated. In Arabidopsis thaliana, several gain-of-function analyses have demonstrated that peptide ligands of the Clavata3 (CLV3)/embryo surrounding region-related (CLE) family are important for maintaining RM size. Here, we demonstrate that a plant U-box E3 ubiquitin ligase, PUB4, is a novel downstream component of CLV3/CLE signaling in the RM. Mutations in PUB4 reduced the inhibitory effect of exogenous CLV3/CLE peptide on root cell proliferation and columella stem cell maintenance. Moreover, pub4 mutants grown without exogenous CLV3/CLE peptide exhibited characteristic phenotypes in the RM, such as enhanced root growth, increased number of cortex/endodermis stem cells and decreased number of columella layers. Our phenotypic and gene expression analyses indicated that PUB4 promotes expression of a cell cycle regulatory gene, CYCD6;1, and regulates formative periclinal asymmetric cell divisions in endodermis and cortex/endodermis initial daughters. These data suggest that PUB4 functions as a global regulator of cell proliferation and the timing of asymmetric cell division that are important for final root architecture. © 2015. Published by The Company of Biologists Ltd.

  9. ETHYLENE-INSENSITIVE5 encodes a 5'-->3' exoribonuclease required for regulation of the EIN3-targeting F-box proteins EBF1/2.

    Science.gov (United States)

    Olmedo, Gabriela; Guo, Hongwei; Gregory, Brian D; Nourizadeh, Saeid D; Aguilar-Henonin, Laura; Li, Hongjiang; An, Fengying; Guzman, Plinio; Ecker, Joseph R

    2006-09-05

    Ethylene is a gaseous plant growth regulator that controls a multitude of developmental and stress responses. Recently, the levels of Arabidopsis EIN3 protein, a key transcription factor mediating ethylene-regulated gene expression, have been demonstrated to increase in response to the presence of ethylene gas. Furthermore, in the absence of ethylene, EIN3 is quickly degraded through a ubiquitin/proteasome pathway mediated by two F-box proteins, EBF1 and EBF2. Here we report the identification of ETHYLENE-INSENSITIVE5 as the 5'-->3' exoribonuclease XRN4. Specifically, we demonstrate that EIN5 is a component of the ethylene signal transduction cascade acting downstream of CTR1 that is required for ethylene-mediated gene expression changes. Furthermore, we find that the ethylene insensitivity of ein5 mutant plants is a consequence of the over-accumulation of EBF1 and EBF2 mRNAs resulting in the under-accumulation of EIN3 even in the presence of ethylene gas. Together, our results suggest that the role of EIN5 in ethylene perception is to antagonize the negative feedback regulation on EIN3 by promoting EBF1 and EBF2 mRNA decay, which consequently allows the accumulation of EIN3 protein to trigger the ethylene response.

  10. Serum levels of high mobility group box 1 protein and its association with quality of life and psychological and functional status in patients with fibromyalgia.

    Science.gov (United States)

    Oktayoglu, Pelin; Tahtasiz, Mehmet; Bozkurt, Mehtap; Em, Serda; Ucar, Demet; Yazmalar, Levent; Mete, Nuriye; Nas, Kemal; Gezer, Orhan

    2013-08-01

    High mobility group box 1 protein (HMGB1) is a proinflammatory cytokine. Previous studies have suggested that HMGB1 can play an important role in the pathogenesis of many rheumatic diseases. The purpose of this study was to investigate the serum levels of HMGB1 in patients with fibromyalgia (FM) and its association with quality of life and psychological and functional status in these patients. Twenty-nine patients who met the 1990 American College of Rheumatology (ACR) criteria for the classification of FM and 29 healthy controls (HC) were included in the present study. Serum samples were collected from both the patients and the HC, and HMGB1 levels were measured by enzyme-linked immunosorbent assay (ELISA). The Fibromyalgia Impact Questionnaire (FIQ) was used to assess the disease severity and functional status in patients with FM. Furthermore, the Nottingham Health Profile was used to assess quality of life in all subjects, as well as the Hospital Anxiety and Depression Scale (HADS) to assess depression and anxiety. The serum levels of HMGB1 protein were positively correlated with the FIQ scores in patients with FM (P = 0.002). Mean serum levels of HMGB1 were higher in patients with FM than in HC but this difference was not statistically significant. HMGB1 protein might be a good laboratory-sourced candidate for the assessment of functional status and disease severity in patients with FM. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  11. Y-box Binding Protein-1 Enhances Oncogenic Transforming Growth Factor β Signaling in Breast Cancer Cells via Triggering Phospho-Activation of Smad2.

    Science.gov (United States)

    Stope, Matthias B; Weiss, Martin; Koensgen, Dominique; Popp, Simone L; Joffroy, Christian; Mustea, Alexander; Buck, Miriam B; Knabbe, Cornelius

    2017-12-01

    Transforming growth factor β (TGFβ) plays a role in diverse oncogenic pathways including cell proliferation and cell motility and is regulated by the pleiotropic factor Y-box binding protein-1 (YB-1). In breast cancer, Sma/Mad related protein 2 (Smad2) represents the most common downstream transducer in TGFβ signaling. Here, YB-1's impact on Smad2 phospho-activation was characterized by incubation of the breast cancer cell line MCF-7 with or without TGFβ1 in the absence or presence of overexpressed YB-1 protein. The phospho-status of Smad2 was assessed via western blotting. Analysis of MCF-7 cells revealed no induction of total Smad2 neither in the presence of TGFβ1, nor during YB-1 overexpression. In contrast, incubation with TGFβ1 led to an increase of phosphorylated Smad2 forms which was significantly amplified by simultaneously overexpressed YB-1 (2.8±0.2-fold). Oncogenic YB-1 indirectly enhances TGFβ signaling cascades via Smad2 phospho-activation and may represent a promising factor for future diagnosis and therapy of breast cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. Functional conservation and divergence of four ginger AP1/AGL9 MADS-box genes revealed by analysis of their expression and protein-protein interaction, and ectopic expression of AhFUL gene in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Xiumei Li

    Full Text Available Alpinia genus are known generally as ginger-lilies for showy flowers in the ginger family, Zingiberaceae, and their floral morphology diverges from typical monocotyledon flowers. However, little is known about the functions of ginger MADS-box genes in floral identity. In this study, four AP1/AGL9 MADS-box genes were cloned from Alpinia hainanensis, and protein-protein interactions (PPIs and roles of the four genes in floral homeotic conversion and in floral evolution are surveyed for the first time. AhFUL is clustered to the AP1 lineage, AhSEP4 and AhSEP3b to the SEP lineage, and AhAGL6-like to the AGL6 lineage. The four genes showed conserved and divergent expression patterns, and their encoded proteins were localized in the nucleus. Seven combinations of PPI (AhFUL-AhSEP4, AhFUL-AhAGL6-like, AhFUL-AhSEP3b, AhSEP4-AhAGL6-like, AhSEP4-AhSEP3b, AhAGL6-like-AhSEP3b, and AhSEP3b-AhSEP3b were detected, and the PPI patterns in the AP1/AGL9 lineage revealed that five of the 10 possible combinations are conserved and three are variable, while conclusions cannot yet be made regarding the other two. Ectopic expression of AhFUL in Arabidopsis thaliana led to early flowering and floral organ homeotic conversion to sepal-like or leaf-like. Therefore, we conclude that the four A. hainanensis AP1/AGL9 genes show functional conservation and divergence in the floral identity from other MADS-box genes.

  13. Dead or alive?

    OpenAIRE

    2006-01-01

    Dead or Alive was a painting and sound exhibition in the National Physical Laboratory (NPL) in Richmond. NPL is the UK’s national standards laboratory for metrology and is one of the world’s leading measurement institutes. \\ud \\ud The exhibition took the form of installations consisting of paintings and soundscapes set up in two spaces, an anechoic chamber (dead) and a reverberation chamber (alive). For the exhibition a new body of work was made including a twenty-seven-metre panoramic painti...

  14. Splice variants of the forkhead box protein AFX exhibit dominant negative activity and inhibit AFXalpha-mediated tumor cell apoptosis.

    Directory of Open Access Journals (Sweden)

    Eun Jig Lee

    2008-07-01

    Full Text Available Loss-of-function in the apoptosis-inducing genes is known to facilitate tumorigenesis. AFX (FOXO4, a member of forkhead transcription factors functions as a tumor suppressor and has 2 isoforms, AFXalpha (505 a.a. and AFXzeta (450 a.a.. In human cancer cells, we identified an N-terminally deleted form of AFXalpha (alpha198-505, translated from a downstream start and 2 short N-terminal AFX proteins (90, and 101 a.a. produced by aberrant splicing.We investigated the expression and role of these AFX variants. Cell transduction study revealed that short N-terminal AFX proteins were not stable. Though alpha(198-505 protein expression was detected in the cytoplasm and nucleus, alpha(198-505 expressing cells did not show a nucleocytoplasmic shuttling mediated by PI3 kinase signaling. Whereas, we observed this shuttling in cells expressing either AFXalpha or AFXzeta protein. AFXzeta and alpha(198-505 lost the ability to transactivate BCL6 or suppress cyclin D2 gene expression. These variants did not induce cancer cell death whereas AFXalpha resulted in apoptosis. We found that AFXzeta and alpha(198-505 suppress the AFXalpha stimulation of BCL6 promoter in a dose dependent manner, indicating dominant negative activity. These variants also inhibited AFXalpha induction of apoptosis.Loss of function by aberrant splicing and the dominant negative activity of AFX variants may provide a mechanism for enhanced survival of neoplastic cells.

  15. Adipocyte spliced form of X-box-binding protein 1 promotes adiponectin multimerization and systemic glucose homeostasis

    NARCIS (Netherlands)

    Sha, H.; Yang, L.; Liu, M.; Xia, S.; Liu, Y.; Liu, F.; Kersten, A.H.; Qi, L.

    2014-01-01

    The physiological role of the spliced form of X-box–binding protein 1 (XBP1s), a key transcription factor of the endoplasmic reticulum (ER) stress response, in adipose tissue remains largely unknown. In this study, we show that overexpression of XBP1s promotes adiponectin multimerization in

  16. Dead reckoner navigation project

    Science.gov (United States)

    Ellis, R.; Sweet, L.

    1981-01-01

    A previous dead reckoner involved a classical gyrocompass, a Hewlett-Packard minicomputer, and a true airspeed sensor. In an effort to bring the cost of this system more in line with the realities of general aviation, recent work was done on replacing the minicomputer with a microcomputer and implementing a fluidic rate sensor in the compass system in place of the directional gyro.

  17. Altered balance between self-reactive T helper (Th)17 cells and Th10 cells and between full-length forkhead box protein 3 (FoxP3) and FoxP3 splice variants in Hashimoto's thyroiditis

    DEFF Research Database (Denmark)

    Kristensen, B; Hegedüs, Laszlo; Madsen, H O

    2015-01-01

    T helper type 17 (Th17) cells play a pathogenic role in autoimmune disease, while interleukin (IL)-10-producing Th10 cells serve a protective role. The balance between the two subsets is regulated by the local cytokine milieu and by the relative expression of intact forkhead box protein 3 (FoxP3)...

  18. The Dead Sea

    Science.gov (United States)

    2006-01-01

    The Dead Sea is the lowest point on Earth at 418 meters below sea level, and also one of the saltiest bodies of water on Earth with a salinity of about 300 parts-per-thousand (nine times greater than ocean salinity). It is located on the border between Jordan and Israel, and is fed by the Jordan River. The Dead Sea is located in the Dead Sea Rift, formed as a result of the Arabian tectonic plate moving northward away from the African Plate. The mineral content of the Dead Sea is significantly different from that of ocean water, consisting of approximately 53% magnesium chloride, 37% potassium chloride and 8% sodium chloride. In the early part of the 20th century, the Dead Sea began to attract interest from chemists who deduced that the Sea was a natural deposit of potash and bromine. From the Dead Sea brine, Israel and Jordan produce 3.8 million tons potash, 200,000 tons elemental bromine, 45,000 tons caustic soda, 25, 000 tons magnesium metal, and sodium chloride. Both countries use extensive salt evaporation pans that have essentially diked the entire southern end of the Dead Sea. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER images Earth to map and monitor the changing surface of our planet. ASTER is one of five Earth-observing instruments launched December 18, 1999, on NASA's Terra satellite. The instrument was built by Japan's Ministry of Economy, Trade and Industry. A joint U.S./Japan science team is responsible for validation and calibration of the instrument and the data products. The broad spectral coverage and high spectral resolution of ASTER provides scientists in numerous disciplines with critical information for surface mapping, and monitoring of dynamic conditions and temporal change. Example applications are: monitoring glacial advances and retreats; monitoring potentially active volcanoes; identifying crop stress; determining

  19. Increased concentrations of C-reactive protein but not high-mobility group box 1 in dogs with naturally occurring sepsis.

    Science.gov (United States)

    Karlsson, I; Wernersson, S; Ambrosen, A; Kindahl, H; Södersten, F; Wang, L; Hagman, R

    2013-11-15

    Sepsis is difficult to diagnose and remains a common mortality cause worldwide in both humans and animals. The uterine infection pyometra causes sepsis in more than half of affected dogs and therefore allows the natural physiological development of sepsis to be studied. To find a sepsis-specific biochemical marker that could be combined with conventional clinical criteria for a more robust and quick diagnosis of sepsis, we measured systemic concentrations of high-mobility group box 1 (HMGB1) in 23 healthy control dogs and in 27 dogs with pyometra, 74% of which had sepsis. We also measured concentrations of the major acute phase protein C-reactive protein (CRP) and an indicator for endotoxaemia, prostaglandin F2α metabolite (PGM) to assess the relative contribution of HMGB1 to the detection of systemic inflammation and endotoxaemia. We found that HMGB1 concentrations, in line with concentrations of CRP and PGM, were significantly increased in dogs with pyometra, and that concentrations of CRP, but not HMGB1, were significantly higher in dogs with sepsis compared to dogs without sepsis. Although serum HMGB1 did not differ between dogs with or without sepsis and was not correlated with either CRP or PGM concentrations, HMGB1 was correlated with the total white blood cell counts, suggesting an independent regulation and involvement in inflammation. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Identification of Y-box binding protein 1 as a core regulator of MEK/ERK pathway-dependent gene signatures in colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Karsten Jürchott

    2010-12-01

    Full Text Available Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. Numerous candidate genes involved in disease and in factors of predictive, as well as of prognostic, value have been deduced from such molecular portraits, e.g. in cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. To identify regulators of transcriptome alterations, we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (RTK/RAS/mitogen-activated protein kinase pathway, computational prediction of regulatory elements in promoters of co-regulated genes, chromatin-based and functional cellular assays. We identified commonly co-regulated, proliferation-associated target genes that respond to the MAPK pathway. We recognized E2F and NFY transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of Y-box binding protein 1 (YBX1 by reporter gene, gel shift, and chromatin immunoprecipitation assays. We also validated the MAPK-dependent gene signature in colorectal cancers and provided evidence for the association of YBX1 with poor prognosis in colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated target genes are involved in executing malignant properties.

  1. Inhibition of Y-box binding protein-1 slows the growth of glioblastoma multiforme and sensitizes to temozolomide independent O6-methylguanine-DNA methyltransferase.

    Science.gov (United States)

    Gao, Yuanyuan; Fotovati, Abbas; Lee, Cathy; Wang, Michelle; Cote, Gilbert; Guns, Emma; Toyota, Brian; Faury, Damien; Jabado, Nada; Dunn, Sandra E

    2009-12-01

    Glioblastoma multiforme (GBM) is an aggressive type of brain tumor where 5 years. In adults, GBM is the most common type of brain tumor. It is rarer in children, where it constitutes approximately 15% of all brain tumors diagnosed. These tumors are often invasive, making surgical resection difficult. Further, they can be refractory to current therapies such as temozolomide. The current dogma is that temozolomide resistance rests on the expression of O6-methylguanine-DNA methyltransferase (MGMT) because it cleaves methylated DNA adducts formed by the drug. Our laboratory recently reported that another drug resistance gene known as the Y-box binding protein-1 (YB-1) is highly expressed in primary GBM but not in normal brain tissues based on the evaluation of primary tumors. We therefore questioned whether GBM depend on YB-1 for growth and/or response to temozolomide. Herein, we report that YB-1 inhibition reduced tumor cell invasion and growth in monolayer as well as in soft agar. Moreover, blocking this protein ultimately delayed tumor onset in mice. Importantly, inhibiting YB-1 enhanced temozolomide sensitivity in a manner that was independent of MGMT in models of adult and pediatric GBM. In conclusion, inhibiting YB-1 may be a novel way to improve the treatment of GBM.

  2. Electrostatic potentials of the S-locus F-box proteins contribute to the pollen S specificity in self-incompatibility in Petunia hybrida.

    Science.gov (United States)

    Li, Junhui; Zhang, Yue; Song, Yanzhai; Zhang, Hui; Fan, Jiangbo; Li, Qun; Zhang, Dongfen; Xue, Yongbiao

    2017-01-01

    Self-incompatibility (SI) is a self/non-self discrimination system found widely in angiosperms and, in many species, is controlled by a single polymorphic S-locus. In the Solanaceae, Rosaceae and Plantaginaceae, the S-locus encodes a single S-RNase and a cluster of S-locus F-box (SLF) proteins to control the pistil and pollen expression of SI, respectively. Previous studies have shown that their cytosolic interactions determine their recognition specificity, but the physical force between their interactions remains unclear. In this study, we show that the electrostatic potentials of SLF contribute to the pollen S specificity through a physical mechanism of 'like charges repel and unlike charges attract' between SLFs and S-RNases in Petunia hybrida. Strikingly, the alteration of a single C-terminal amino acid of SLF reversed its surface electrostatic potentials and subsequently the pollen S specificity. Collectively, our results reveal that the electrostatic potentials act as a major physical force between cytosolic SLFs and S-RNases, providing a mechanistic insight into the self/non-self discrimination between cytosolic proteins in angiosperms. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  3. Peroxiredoxins, thioredoxin, and Y-box-binding protein-1 are involved in the pathogenesis and progression of dialysis-associated renal cell carcinoma.

    Science.gov (United States)

    Fushimi, Fumiyoshi; Taguchi, Kenichi; Izumi, Hiroto; Kohno, Kimitoshi; Kuwano, Michihiko; Ono, Mayumi; Nakashima, Yutaka; Takesue, Tetsuro; Naito, Seiji; Oda, Yoshinao

    2013-10-01

    Patients with end-stage renal disease are exposed to increased oxidative stress and impairment of antioxidant mechanisms. We focused on dialysis renal cell carcinoma (RCC), including epithelial hyperplasia in acquired cystic disease of the kidney (ACDK). We attempted to obtain insight into the carcinogenesis and tumor progression in terms of cellular defense mechanisms associated with oxidative stress by investigating the expression of antioxidant proteins by immunohistochemistry. We evaluated retrospectively 43 cases of dialysis RCC and, as a control group, 49 cases of sporadic RCC. Peroxiredoxin (Prx) 1, 3, 4, 5, and 6 expression in dialysis RCC was positively correlated with the duration of dialysis. In epithelial hyperplasia, in 17 cases of acquired cystic disease of the kidney, Prxs and thioredoxin were highly expressed. Moreover, in dialysis RCC, Prx 3, 4, and 5 immunoreactivity and nuclear expression of Y-box-binding protein-1 were higher than in sporadic RCC. In dialysis RCC, Prx 3, 4, and 5 immunoreactivity positively correlated with the Fuhrman nuclear grade. These data suggest that oxidative stress during dialysis enhances antioxidant activity, with an inhibiting effect on carcinogenesis. Once cancer has developed, antioxidant activity might have a stimulating effect on the progression of dialysis RCC.

  4. Nuclear detection of Y-box protein-1 (YB-1) closely associates with progesterone receptor negativity and is a strong adverse survival factor in human breast cancer

    International Nuclear Information System (INIS)

    Dahl, Edgar; Dunn, Sandra E; Mertens, Peter R; En-Nia, Abdelaziz; Wiesmann, Frank; Krings, Renate; Djudjaj, Sonja; Breuer, Elisabeth; Fuchs, Thomas; Wild, Peter J; Hartmann, Arndt

    2009-01-01

    Y-box binding protein-1 (YB-1) is the prototypic member of the cold shock protein family that fulfills numerous cellular functions. In the nucleus YB-1 protein orchestrates transcription of proliferation-related genes, whereas in the cytoplasm it associates with mRNA and directs translation. In human tumor entities, such as breast, lung and prostate cancer, cellular YB-1 expression indicates poor clinical outcome, suggesting that YB-1 is an attractive marker to predict patients' prognosis and, potentially, is suitable to individualize treatment protocols. Given these predictive qualities of YB-1 detection we sought to establish a highly specific monoclonal antibody (Mab) for diagnostic testing and its characterization towards outcome prediction (relapse-free and overall survival). Hybridoma cell generation was carried out with recombinant YB-1 protein as immunogen and Mab characterization was performed using immunoblotting and ELISA with recombinant and tagged YB-1 proteins, as well as immunohistochemistry of healthy and breast cancer specimens. Breast tumor tissue array staining results were analyzed for correlations with receptor expression and outcome parameters. YB-1-specific Mab F-E2G5 associates with conformational binding epitopes mapping to two domains within the N-terminal half of the protein and detects nuclear YB-1 protein by immunohistochemistry in paraffin-embedded breast cancer tissues. Prognostic evaluation of Mab F-E2G5 was performed by immunohistochemistry of a human breast cancer tissue microarray comprising 179 invasive breast cancers, 8 ductal carcinoma in situ and 37 normal breast tissue samples. Nuclear YB-1 detection in human breast cancer cells was associated with poor overall survival (p = 0.0046). We observed a close correlation between nuclear YB-1 detection and absence of progesterone receptor expression (p = 0.002), indicating that nuclear YB-1 detection marks a specific subgroup of breast cancer. Likely due to limitation of sample

  5. Nuclear detection of Y-box protein-1 (YB-1 closely associates with progesterone receptor negativity and is a strong adverse survival factor in human breast cancer

    Directory of Open Access Journals (Sweden)

    Wild Peter J

    2009-11-01

    Full Text Available Abstract Background Y-box binding protein-1 (YB-1 is the prototypic member of the cold shock protein family that fulfills numerous cellular functions. In the nucleus YB-1 protein orchestrates transcription of proliferation-related genes, whereas in the cytoplasm it associates with mRNA and directs translation. In human tumor entities, such as breast, lung and prostate cancer, cellular YB-1 expression indicates poor clinical outcome, suggesting that YB-1 is an attractive marker to predict patients' prognosis and, potentially, is suitable to individualize treatment protocols. Given these predictive qualities of YB-1 detection we sought to establish a highly specific monoclonal antibody (Mab for diagnostic testing and its characterization towards outcome prediction (relapse-free and overall survival. Methods Hybridoma cell generation was carried out with recombinant YB-1 protein as immunogen and Mab characterization was performed using immunoblotting and ELISA with recombinant and tagged YB-1 proteins, as well as immunohistochemistry of healthy and breast cancer specimens. Breast tumor tissue array staining results were analyzed for correlations with receptor expression and outcome parameters. Results YB-1-specific Mab F-E2G5 associates with conformational binding epitopes mapping to two domains within the N-terminal half of the protein and detects nuclear YB-1 protein by immunohistochemistry in paraffin-embedded breast cancer tissues. Prognostic evaluation of Mab F-E2G5 was performed by immunohistochemistry of a human breast cancer tissue microarray comprising 179 invasive breast cancers, 8 ductal carcinoma in situ and 37 normal breast tissue samples. Nuclear YB-1 detection in human breast cancer cells was associated with poor overall survival (p = 0.0046. We observed a close correlation between nuclear YB-1 detection and absence of progesterone receptor expression (p = 0.002, indicating that nuclear YB-1 detection marks a specific subgroup of

  6. Dead-ice environments

    DEFF Research Database (Denmark)

    Krüger, Johannes; Kjær, Kurt H.; Schomacker, Anders

    2010-01-01

    Kötlujökull transports considerable amounts of supraglacial debris at its snout because of frontal oscillations with frequent ice advances followed by ice-margin stagnation. Kötlujökull provides suitable conditions of studying dead-ice melting and landscape formation in a debris-charged lowland...... under humid, sub-polar conditions? Does this rate differ from rates reported from polar environments of dry continental nature? How will the sedimentary architecture appear in the geological record? How will the final landsystem appear? These key questions are answered in a review of research...... and conclusions on dead-ice melting and landscape formation from Kötlujökull. Processes and landform-sediment associations are linked to the current climate and glacier–volcano interaction....

  7. Dead-ice environments

    DEFF Research Database (Denmark)

    Krüger, Johannes; Kjær, Kurt H.; Schomacker, Anders

    2010-01-01

    Kötlujökull transports considerable amounts of supraglacial debris at its snout because of frontal oscillations with frequent ice advances followed by ice-margin stagnation. Kötlujökull provides suitable conditions of studying dead-ice melting and landscape formation in a debris-charged lowland...... glacier environment. The scientific challenges are to answer the key questions. What are the conditions for dead-ice formation? From which sources does the sediment cover originate? Which melting and reworking processes act in the ice-cored moraines? What is the rate of de-icing in the ice-cored moraines...... under humid, sub-polar conditions? Does this rate differ from rates reported from polar environments of dry continental nature? How will the sedimentary architecture appear in the geological record? How will the final landsystem appear? These key questions are answered in a review of research...

  8. Forkhead Box Protein 1 (FoxO1) Inhibits Accelerated β Cell Aging in Pancreas-specific SMAD7 Mutant Mice.

    Science.gov (United States)

    Xiao, Xiangwei; Chen, Congde; Guo, Ping; Zhang, Ting; Fischbach, Shane; Fusco, Joseph; Shiota, Chiyo; Prasadan, Krishna; Dong, Henry; Gittes, George K

    2017-02-24

    The mechanisms underlying the effects of exocrine dysfunction on the development of diabetes remain largely unknown. Here we show that pancreatic depletion of SMAD7 resulted in age-dependent increases in β cell dysfunction with accelerated glucose intolerance, followed by overt diabetes. The accelerated β cell dysfunction and loss of proliferation capacity, two features of β cell aging, appeared to be non-cell-autonomous, secondary to the adjacent exocrine failure as a "bystander effect." Increased Forkhead box protein 1 (FoxO1) acetylation and nuclear retention was followed by progressive FoxO1 loss in β cells that marked the onset of diabetes. Moreover, forced FoxO1 expression in β cells prevented β cell dysfunction and loss in this model. Thus, we present a model of accelerated β cell aging that may be useful for studying the mechanisms underlying β cell failure in diabetes. Moreover, we provide evidence highlighting a critical role of FoxO1 in maintaining β cell identity in the context of SMAD7 failure. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Forkhead Box Protein 1 (FoxO1) Inhibits Accelerated β Cell Aging in Pancreas-specific SMAD7 Mutant Mice*

    Science.gov (United States)

    Xiao, Xiangwei; Chen, Congde; Guo, Ping; Zhang, Ting; Fischbach, Shane; Fusco, Joseph; Shiota, Chiyo; Prasadan, Krishna; Dong, Henry; Gittes, George K.

    2017-01-01

    The mechanisms underlying the effects of exocrine dysfunction on the development of diabetes remain largely unknown. Here we show that pancreatic depletion of SMAD7 resulted in age-dependent increases in β cell dysfunction with accelerated glucose intolerance, followed by overt diabetes. The accelerated β cell dysfunction and loss of proliferation capacity, two features of β cell aging, appeared to be non-cell-autonomous, secondary to the adjacent exocrine failure as a “bystander effect.” Increased Forkhead box protein 1 (FoxO1) acetylation and nuclear retention was followed by progressive FoxO1 loss in β cells that marked the onset of diabetes. Moreover, forced FoxO1 expression in β cells prevented β cell dysfunction and loss in this model. Thus, we present a model of accelerated β cell aging that may be useful for studying the mechanisms underlying β cell failure in diabetes. Moreover, we provide evidence highlighting a critical role of FoxO1 in maintaining β cell identity in the context of SMAD7 failure. PMID:28057752

  10. Role of Bone Marrow Maturity, Insulin-Like Growth Factor 1 Receptor, and Forkhead Box Protein N1 in Thymic Involution and Rejuvenation.

    Science.gov (United States)

    Tasaki, M; Villani, V; Shimizu, A; Sekijima, M; Yamada, R; Hanekamp, I M; Hanekamp, J S; Cormack, T A; Moran, S G; Kawai, A; Sachs, D H; Yamada, K

    2016-10-01

    Thymic involution is associated with age-related changes of the immune system. Utilizing our innovative technique of transplantation of a thymus as an isolated vascularized graft in MHC-inbred miniature swine, we have previously demonstrated that aged thymi are rejuvenated after transplantation into juvenile swine. Here we have studied the role of insulin-like growth factor (IGF) and forkhead-box protein-N1 (FOXN1) as well as bone marrow (BM) in thymic rejuvenation and involution. We examined thymic rejuvenation and involution by means of histology and flow cytometry. Thymic function was assessed by the ability to induce tolerance of allogeneic kidneys. Aged thymi were rejuvenated in a juvenile environment, and successfully induced organ tolerance, while juvenile thymi in aged recipients involuted and had a limited ability to induce tolerance. However, juvenile BM inhibited the involution process of juvenile thymi in aged recipients. An elevated expression of both FOXN1 and IGF1 receptors (IGF-1R) was observed in juvenile thymi and rejuvenated thymi. Juvenile BM plays a role in promoting the local thymic milieu as indicated by its ability to inhibit thymic involution in aged animals. The expression of FOXN1 and IGF-1R was noted to increase under conditions that stimulated rejuvenation, suggesting that these factors are involved in thymic recovery. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  11. High mobility group box protein-1 promotes cerebral edema after traumatic brain injury via activation of toll-like receptor 4.

    Science.gov (United States)

    Laird, Melissa D; Shields, Jessica S; Sukumari-Ramesh, Sangeetha; Kimbler, Donald E; Fessler, R David; Shakir, Basheer; Youssef, Patrick; Yanasak, Nathan; Vender, John R; Dhandapani, Krishnan M

    2014-01-01

    Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Cerebral edema, a life-threatening medical complication, contributes to elevated intracranial pressure (ICP) and a poor clinical prognosis after TBI. Unfortunately, treatment options to reduce post-traumatic edema remain suboptimal, due in part, to a dearth of viable therapeutic targets. Herein, we tested the hypothesis that cerebral innate immune responses contribute to edema development after TBI. Our results demonstrate that high-mobility group box protein 1 (HMGB1) was released from necrotic neurons via a NR2B-mediated mechanism. HMGB1 was clinically associated with elevated ICP in patients and functionally promoted cerebral edema after TBI in mice. The detrimental effects of HMGB1 were mediated, at least in part, via activation of microglial toll-like receptor 4 (TLR4) and the subsequent expression of the astrocytic water channel, aquaporin-4 (AQP4). Genetic or pharmacological (VGX-1027) TLR4 inhibition attenuated the neuroinflammatory response and limited post-traumatic edema with a delayed, clinically implementable therapeutic window. Human and rodent tissue culture studies further defined the cellular mechanisms demonstrating neuronal HMGB1 initiates the microglial release of interleukin-6 (IL-6) in a TLR4 dependent mechanism. In turn, microglial IL-6 increased the astrocytic expression of AQP4. Taken together, these data implicate microglia as key mediators of post-traumatic brain edema and suggest HMGB1-TLR4 signaling promotes neurovascular dysfunction after TBI. Copyright © 2013 Wiley Periodicals, Inc.

  12. Positive expression of Y-box binding protein 1 and prognosis in non-small cell lung cancer: a meta-analysis.

    Science.gov (United States)

    Jiang, Liang; Yuan, Gao-Le; Liang, Qi-Lian; Zhang, Hui-Jie; Huang, Jie; Cheng, Shao-Ang; Peng, Xiao-Xia

    2017-08-15

    Y-box binding protein 1 (YB-1) belongs to the cold shock domain protein family involved in transcription and translation. We conducted a meta-analysis of the association between YB-1 expression and the survival and clinicopathological features in NSCLC. PubMed and Embase were searched to identify studies that evaluated the YB-1 expression (by immunohistochemistry) and overall survival (OS) in NSCLC. Hazard ratios (HRs) and 95% confidence intervals (CI) of OS were pooled. Odds ratios (ORs) of clinicopathological features were computed. Meta-analysis was performed using STATA 12.0 software. Data on 692 NSCLC patients were collected from six eligible studies. Meta-analysis revealed that YB-1 was associated with worse OS (HR = 1.59, 95% CI [1.27, 2.00], P fixed effect), tumor stage (OR = 0.43, 95% CI [0.22-0.82], P = 0.01, random effect), and depth of invasion (OR = 0.37, 95%CI [0.22-0.63], P fixed effect). A subgroup was analyzed by IHC staining to determine the location of YB-1 positive expression. Poor OS was observed in nucleus staining (pooled HR = 1.86, 95% CI [1.41, 2.45], P < 0.001). However, no statistical significance was observed in combined cytoplasmic and nuclear staining (pooled HR = 1.14, 95% CI [0.76, 1.72], P = 0.536). Meta-analysis indicated that YB-1 overexpression is correlated with worse OS and clinicopathological features in NSCLC. Subgroup analysis revealed that the nucleus expression of YB-1 may be more closely associated with NSCLC prognosis than cytoplasmic expression.

  13. Expression of ankyrin repeat and suppressor of cytokine signaling box protein 4 (Asb-4) in proopiomelanocortin neurons of the arcuate nucleus of mice produces a hyperphagic, lean phenotype.

    Science.gov (United States)

    Li, Ji-Yao; Chai, Biao-Xin; Zhang, Weizhen; Wang, Hui; Mulholland, Michael W

    2010-01-01

    Ankyrin repeat and suppressor of cytokine signaling box-containing protein 4 (Asb-4) is specifically expressed in the energy homeostasis-related brain areas and colocalizes with proopiomelanocortin (POMC) neurons of the arcuate nucleus (ARC). Injection of insulin into the third ventricle of the rat brain increased Asb-4 mRNA expression in the paraventricular nucleus but not in the ARC of the hypothalamus, whereas injection of leptin (ip) increased Asb-4 expression in both mouse paraventricular nucleus and ARC. A transgenic mouse in which Myc-tagged Asb-4 is specifically expressed in POMC neurons of the ARC was made and used to study the effects of Asb-4 on ingestive behavior and metabolic rate. Animals with overexpression of Asb-4 in POMC neurons demonstrated an increase in food intake. However, POMC-Asb-4 transgenic animals gained significantly less weight from 6-30 wk of age. The POMC-Asb-4 mice had reduced fat mass and increased lean mass and lower levels of blood leptin. The transgenic animals were resistant to high-fat diet-induced obesity. Transgenic mice had significantly higher rates of oxygen consumption and carbon dioxide production than wild-type mice during both light and dark periods. The locomotive activity of transgenic mice was increased. The overexpression of Asb-4 in POMC neurons increased POMC mRNA expression in the ARC. The transgenic animals had no observed effect on peripheral glucose metabolism and the activity of the autonomic nervous system. These results indicate that Asb-4 is a key regulatory protein in the central nervous system, involved in the control of feeding behavior and metabolic rate.

  14. Laryngeal (Voice Box) Cancer

    Science.gov (United States)

    ... ENTCareers Marketplace Find an ENT Doctor Near You Voice Box (Laryngeal) Cancer Voice Box (Laryngeal) Cancer Patient Health Information News media ... laryngeal cancer can be severe with respect to voice, breathing, or swallowing. It is fundamentally a preventable ...

  15. The p63 protein isoform ΔNp63α modulates Y-box binding protein 1 in its subcellular distribution and regulation of cell survival and motility genes.

    Science.gov (United States)

    Di Costanzo, Antonella; Troiano, Annaelena; di Martino, Orsola; Cacace, Andrea; Natale, Carlo F; Ventre, Maurizio; Netti, Paolo; Caserta, Sergio; Pollice, Alessandra; La Mantia, Girolama; Calabrò, Viola

    2012-08-31

    The Y-box binding protein 1 (YB-1) belongs to the cold-shock domain protein superfamily, one of the most evolutionarily conserved nucleic acid-binding proteins currently known. YB-1 performs a wide variety of cellular functions, including transcriptional and translational regulation, DNA repair, drug resistance, and stress responses to extracellular signals. Inasmuch as the level of YB-1 drastically increases in tumor cells, this protein is considered to be one of the most indicative markers of malignant tumors. Here, we present evidence that ΔNp63α, the predominant p63 protein isoform in squamous epithelia and YB-1, can physically interact. Into the nucleus, ΔNp63α and YB-1 cooperate in PI3KCA gene promoter activation. Moreover, ΔNp63α promotes YB-1 nuclear accumulation thereby reducing the amount of YB-1 bound to its target transcripts such as that encoding the SNAIL1 protein. Accordingly, ΔNp63α enforced expression was associated with a reduction of the level of SNAIL1, a potent inducer of epithelial to mesenchymal transition. Furthermore, ΔNp63α depletion causes morphological change and enhanced formation of actin stress fibers in squamous cancer cells. Mechanistic studies indicate that ΔNp63α affects cell movement and can reverse the increase of cell motility induced by YB-1 overexpression. These data thus suggest that ΔNp63α provides inhibitory signals for cell motility. Deficiency of ΔNp63α gene expression promotes cell mobilization, at least partially, through a YB-1-dependent mechanism.

  16. Self-Interaction Chromatography of mAbs: Accurate Measurement of Dead Volumes.

    Science.gov (United States)

    Hedberg, S H M; Heng, J Y Y; Williams, D R; Liddell, J M

    2015-12-01

    Measurement of the second virial coefficient B22 for proteins using self-interaction chromatography (SIC) is becoming an increasingly important technique for studying their solution behaviour. In common with all physicochemical chromatographic methods, measuring the dead volume of the SIC packed column is crucial for accurate retention data; this paper examines best practise for dead volume determination. SIC type experiments using catalase, BSA, lysozyme and a mAb as model systems are reported, as well as a number of dead column measurements. It was observed that lysozyme and mAb interacted specifically with Toyopearl AF-Formyl dead columns depending upon pH and [NaCl], invalidating their dead volume usage. Toyopearl AF-Amino packed dead columns showed no such problems and acted as suitable dead columns without any solution condition dependency. Dead volume determinations using dextran MW standards with protein immobilised SIC columns provided dead volume estimates close to those obtained using Toyopearl AF-Amino dead columns. It is concluded that specific interactions between proteins, including mAbs, and select SIC support phases can compromise the use of some standard approaches for estimating the dead volume of SIC columns. Two other methods were shown to provide good estimates for the dead volume.

  17. The Dead Walk

    Directory of Open Access Journals (Sweden)

    Bill Phillips

    2014-02-01

    Full Text Available Monsters have always enjoyed a significant presence in the human imagination, and religion was instrumental in replacing the physical horror they engendered with that of a moral threat. Zombies, however, are amoral – their motivation purely instinctive and arbitrary, yet they are, perhaps, the most loathed of all contemporary monsters. One explanation for this lies in the theory of the uncanny valley, proposed by robotics engineer Masahiro Mori. According to the theory, we reserve our greatest fears for those things which seem most human, yet are not – such as dead bodies. Such a reaction is most likely a survival mechanism to protect us from danger and disease – a mechanism even more essential when the dead rise up and walk. From their beginnings zombies have reflected western societies’ greatest fears – be they of revolutionary Haitians, women, or communists. In recent years the rise in the popularity of the zombie in films, books and television series reflects our fears for the planet, the economy, and of death itself

  18. Celastrol pretreatment attenuates rat myocardial ischemia/ reperfusion injury by inhibiting high mobility group boxprotein expression via the PI3K/Akt pathway.

    Science.gov (United States)

    Tong, Suiyang; Zhang, Liangliang; Joseph, Jacob; Jiang, Xuejun

    2018-03-11

    Celastrol pretreatment has been shown to protect against myocardial ischemia/reperfusion (I/R) injury, but the underlying mechanism is poorly understood. This study aimed to investigate the cardioprotective effects of celastrol pretreatment on I/R injury and to further explore whether its mechanism of action was associated with the inhibition of high mobility group box 1 protein (HMGB1) expression via the phosphoinositide 3-kinase (PI3K)/Akt pathway. In a fixed-dose study, hematoxylin and eosin staining and myocardial enzyme measurements were used to determine the optimal dose of celastrol that elicited the best cardioprotective effects against I/R injury. Furthermore, rats were pretreated with 4 mg/kg celastrol, and infarct size and the levels of myocardial enzymes, apoptosis, inflammatory and oxidative indices, and HMGB1 and p-Akt expression were measured. Our results indicated that celastrol dose-dependently attenuated histopathological changes and the elevation in myocardial enzymes induced by I/R. Moreover, the celastrol pretreatment (4 mg/kg) not only significantly decreased infarct size as well as myocardial enzyme levels but also inhibited myocardial apoptosis, inflammatory response and oxidative stress. Additionally, celastrol downregulated HMGB1 expression and upregulated p-Akt expression in the myocardium. LY294002, a specific pI3k inhibitor, partially reversed the decreased HMGB1 expression, increased p-Akt expression induced by celastrol, and abolished the anti-apoptotic, anti-inflammatory and anti-oxidative effects of celastrol. These findings suggest that short-term pretreatment with celastrol protects against myocardial I/R injury by suppressing myocardial apoptosis, inflammatory response and oxidative stress via pI3k/Akt pathway activation and HMGB1 inhibition. Copyright © 2018. Published by Elsevier Inc.

  19. High mobility group box 1 protein synergizes with lipopolysaccharide and peptidoglycan for nitric oxide production in mouse peritoneal macrophages in vitro.

    Science.gov (United States)

    Chakraborty, Rituparna; Bhatt, Kunal H; Sodhi, Ajit

    2013-05-01

    Extracellular high mobility group box 1 (HMGB1) protein and nitric oxide (NO) has been credited with multiple inflammatory functions using in vivo and in vitro systems. Therefore, delineating their regulation may be an important therapeutic strategy for the treatment of sepsis. In the present study, it is demonstrated that recombinant HMGB1 (rHMGB1) synergizes with sub threshold concentration of TLR2 agonist (PGN; 1 μg/ml) as well as with TLR4 agonist (LPS; 1 ng/ml) to induce NO release in mouse peritoneal macrophages. The enhanced iNOS expression was also observed at the transcription and translational level. Co-incubation of macrophages with rHMGB1 with either PGN or LPS showed enhanced expression of TLR2, TLR4 and RAGE. TLR2, TLR4 or RAGE knockdown macrophages effectively inhibited the rHMGB1+PGN or LPS induced NO synergy. It was further observed that the JNK MAPK inhibitor SP600125 attenuated the PGN+rHMGB1 induced iNOS/NO synergy whereas p38 MAPK inhibitor SB908912 inhibited iNOS/NO synergy induced by LPS+rHMGB1. It was also observed that the activation of NF-κB is essential for the synergy as the pharmacological inhibition or siRNA knockdown of NF-κB (cRel) significantly reduced the rHMGB1+PGN or rHMGB1+LPS induced enhanced iNOS/NO expression. Altogether, the data suggests that the co-incubation of macrophages with rHMGB1 with either LPS or PGN induces the synergistic effect on iNOS expression and NO release by the upregulation of surface receptors (TLR2, TLR4 and RAGE) which in turn amplifies the MAPKs (p38 and JNK) and NF-κB activation and results in enhanced iNOS expression and NO production. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. The Entamoeba histolytica TBP and TRF1 transcription factors are GAAC-box binding proteins, which display differential gene expression under different stress stimuli and during the interaction with mammalian cells.

    Science.gov (United States)

    Narayanasamy, Ravi Kumar; Castañón-Sanchez, Carlos Alberto; Luna-Arias, Juan Pedro; García-Rivera, Guillermina; Avendaño-Borromeo, Bartolo; Labra-Barrios, María Luisa; Valdés, Jesús; Herrera-Aguirre, María Esther; Orozco, Esther

    2018-03-07

    Entamoeba histolytica is the protozoan parasite responsible for human amebiasis. It causes up to 100,000 deaths worldwide each year. This parasite has two closely related basal transcription factors, the TATA-box binding protein (EhTBP) and the TBP-related factor 1 (EhTRF1). TBP binds to the canonical TATTTAAA-box, as well as to different TATA variants. TRF1 also binds to the TATTTAAA-box. However, their binding capacity to diverse core promoter elements, including the GAAC-element, and their role in gene regulation in this parasite remains unknown. EMSA experiments were performed to determine the binding capacity of recombinant TBP and TRF1 to TATA variants, GAAC and GAAC-like boxes. For the functional analysis under different stress stimuli (e.g. growth curve, serum depletion, heat-shock, and UV-irradiation) and during the interaction with mammalian cells (erythrocytes, MDCK cell monolayers, and hepatocytes of hamsters), RT-qPCR, and gene knockdown were performed. Both transcription factors bound to the different TATA variants tested, as well as to the GAAC-boxes, suggesting that they are GAAC-box-binding proteins. The K D values determined for TBP and TRF1 for the different TATA variants and GAAC-box were in the range of 10 -12  M to 10 -11  M. During the death phase of growth or in serum depletion, Ehtbp mRNA levels significantly increased, whereas the mRNA level of Ehtrf1 did not change under these conditions. Ehtrf1 gene expression was negatively regulated by UV-irradiation and heat-shock stress, with no changes in Ehtbp gene expression. Moreover, Ehtrf1 gene also showed a negative regulation during erythrophagocytosis, liver abscess formation, and a transient expression level increase at the initial phase of MDCK cell destruction. Finally, the Ehtbp gene knockdown displayed a drastic decrease in the efficiency of erythrophagocytosis in G3 trophozoites. To our knowledge, this study reveals that these basal transcription factors are able to bind multiple

  1. Shaping 3-D boxes

    DEFF Research Database (Denmark)

    Stenholt, Rasmus; Madsen, Claus B.

    2011-01-01

    Enabling users to shape 3-D boxes in immersive virtual environments is a non-trivial problem. In this paper, a new family of techniques for creating rectangular boxes of arbitrary position, orientation, and size is presented and evaluated. These new techniques are based solely on position data......F) docking experiment against an existing technique, which requires the user to perform the rotation and scaling of the box explicitly. The precision of the users' box construction is evaluated by a novel error metric measuring the difference between two boxes. The results of the experiment strongly indicate...

  2. Control of Paternally Expressed Imprinted UPWARD CURLY LEAF1, a Gene Encoding an F-Box Protein That Regulates CURLY LEAF Polycomb Protein, in the Arabidopsis Endosperm.

    Directory of Open Access Journals (Sweden)

    Cheol Woong Jeong

    Full Text Available Genomic imprinting, an epigenetic process in mammals and flowering plants, refers to the differential expression of alleles of the same genes in a parent-of-origin-specific manner. In Arabidopsis, imprinting occurs primarily in the endosperm, which nourishes the developing embryo. Recent high-throughput sequencing analyses revealed that more than 200 loci are imprinted in Arabidopsis; however, only a few of these imprinted genes and their imprinting mechanisms have been examined in detail. Whereas most imprinted loci characterized to date are maternally expressed imprinted genes (MEGs, PHERES1 (PHE1 and ADMETOS (ADM are paternally expressed imprinted genes (PEGs. Here, we report that UPWARD CURLY LEAF1 (UCL1, a gene encoding an E3 ligase that degrades the CURLY LEAF (CLF polycomb protein, is a PEG. After fertilization, paternally inherited UCL1 is expressed in the endosperm, but not in the embryo. The expression pattern of a β-glucuronidase (GUS reporter gene driven by the UCL1 promoter suggests that the imprinting control region (ICR of UCL1 is adjacent to a transposable element in the UCL1 5'-upstream region. Polycomb Repressive Complex 2 (PRC2 silences the maternal UCL1 allele in the central cell prior to fertilization and in the endosperm after fertilization. The UCL1 imprinting pattern was not affected in paternal PRC2 mutants. We found unexpectedly that the maternal UCL1 allele is reactivated in the endosperm of Arabidopsis lines with mutations in cytosine DNA METHYLTRANSFERASE 1 (MET1 or the DNA glycosylase DEMETER (DME, which antagonistically regulate CpG methylation of DNA. By contrast, maternal UCL1 silencing was not altered in mutants with defects in non-CpG methylation. Thus, silencing of the maternal UCL1 allele is regulated by both MET1 and DME as well as by PRC2, suggesting that divergent mechanisms for the regulation of PEGs evolved in Arabidopsis.

  3. The PCNA interaction protein box sequence in Rad54 is an integral part of its ATPase domain and is required for efficient DNA repair and recombination

    DEFF Research Database (Denmark)

    Burgess, Rebecca C; Sebesta, Marek; Sisakova, Alexandra

    2013-01-01

    was defective in primer extension at the MAT locus as well as in vitro, but additional biochemical analysis revealed that this mutant also had diminished ATPase activity and an inability to promote D-loop formation. Further mutational analysis of the putative PIP-box uncovered that other phenotypically relevant...... mutants in this domain also resulted in a loss of ATPase activity. Therefore, we have found that although Rad54 interacts with PCNA, the PIP-box motif likely plays only a minor role in stabilizing the PCNA interaction, and rather, this conserved domain is probably an extension of the ATPase domain III....

  4. Forkhead box protein P3 (Foxp3) expression serves as an early chronic inflammation marker of squamous cell differentiation and aggressive pathology of urothelial carcinomas in neurological patients.

    Science.gov (United States)

    Phé, Véronique; Rouprêt, Morgan; Cussenot, Olivier; Chartier-Kastler, Emmanuel; Gamé, Xavier; Compérat, Eva

    2015-04-01

    To establish whether the expression of forkhead box protein P3 (Foxp3) provides specific diagnostic information about neurological patients with urothelial carcinoma of the bladder (UCB). UCB tissue samples from neurological patients were retrieved and compared with control samples. The expression of Foxp3 was analysed via immunohistochemistry of microarray tissue sections. The correlation between Foxp3 expression, histological parameters and tumour stage was assessed. Overall, 20 UCB tissue samples and 20 others without UCB from neurological patients, and 46 UCB tissue samples from non-neurological patients were analysed. The distribution of pT of UCB in the neurological patients was as follows: one low-grade pTa (5%), three high-grade pTa (15%), three pT1(15%), one pT2(5%), seven pT3(35%) and five pT4(25%). Squamous cell differentiation was seen in nine UCB samples (45%). Foxp3 expression was detected in tumour tissues, including one pTa high grade, one pT1, one pT2, five pT3 and five pT4 tumours. Foxp3 was expressed in 11/13 muscle-invasive tumours. All tumours displaying squamous cell differentiation expressed Foxp3. Foxp3 was not expressed in the pT3 tumours that displayed sarcomatoid and micropapillary properties. Among the bladder samples without UCB from neurological patients, no expression of Foxp3 was observed. Among the UCB samples from the non-neurological patients, only seven displayed squamous cell differentiation. All tumours that displayed squamous cell differentiation expressed Foxp3, including one pTa high grade, four pT3 and two pT4 tumours. Other tumours displaying urothelial differentiation did not express Foxp3. The expression of Foxp3 correlated to squamous cell differentiation in neurological (P = 0.004) and non-neurological UCB tissue (P differentiation. Targeting Foxp3 may represent a novel strategy to improve anti-tumour immunotherapy for UCB. © 2015 The Authors. BJU International © 2015 BJU International.

  5. Promotional effect of microRNA-194 on breast cancer cells via targeting F-box/WD repeat-containing protein 7.

    Science.gov (United States)

    Chen, Yaomin; Wei, Haiyan; Liu, Yu; Zheng, Shusen

    2018-04-01

    Breast cancer is the most common type of malignant cancer in females. An increasing number of studies have revealed that microRNAs (miR), which belong to a class of small non-coding RNAs, serve an important role in a number of human cancer subtypes. In the present study, the role of miR-194 in breast cancer cells and its underlying mechanisms were investigated. The results demonstrated that the serum levels of miR-194 were significantly higher in patients of the poorly differentiated and well-differentiated groups, compared with in healthy adults. Additionally, the serum level of miR-194 was significantly higher in the poorly differentiated group compared with in the well-differentiated group. In order to further investigate the role of miR-194 in breast cancer cells, the present study transfected two breast cancer cell lines, MCF-7 and MDA-MB-231, with an empty vector (control), miR-194 (overexpression), antagomiR-194 (inhibitor, functional knock down) or antagomiR-194 and miR-194. An MTT assay was performed in order to detect the proliferation of breast cancer cells in the various groups. The results revealed that the overexpression of miR-194 significantly accelerated cell proliferation, whereas the inhibition of miR-194 significantly decelerated the proliferation of MCF-7 and MDA-MB-231 cells. Furthermore, the expression levels of cyclin D and cyclin E were significantly upregulated in miR-194 overexpressing cells, and the expression levels of cyclin D and cyclin E were significantly downregulated in miR-194 inhibited cells, as compared with in control cells. No significant change was observed in the level of proliferation of cells co-transfected with miR-194 and antagomiR-194, compared with in the control cells. According to the hypothesis suggesting possible target genes of miR-194, the present study proposed that F-box/WD repeat-containing protein 7 ( Fbxw-7 ) may be a direct target of miR-194, which was confirmed by a luciferase reporter assay. The present

  6. An epidemiological investigation of a Forkhead box protein E3 founder mutation underlying the high frequency of sclerocornea, aphakia, and microphthalmia in a Mexican village.

    Science.gov (United States)

    Pantoja-Melendez, Carlos; Ali, Manir; Zenteno, Juan C

    2013-01-01

    To investigate the molecular epidemiological basis for the unusually high incidence of sclerocornea, aphakia, and microphthalmia in a village in the Tlaxcala province of central Mexico. A population census was performed in a village to identify all sclerocornea, aphakia, and microphthalmia cases. Molecular analysis of the previously identified Forkhead box protein E3 (FOXE3) mutation, c.292T>C (p.Y98H), was performed with PCR amplification and direct DNA sequencing. In addition, DNA from 405 randomly selected unaffected villagers was analyzed to establish the carrier frequency of the causal mutation. To identify the number of generations since the mutation arose in the village, 17 polymorphic markers distributed in a region of 6 Mb around the mutated locus were genotyped in the affected individuals, followed by DMLE software analysis to calculate mutation age. A total of 22 patients with sclerocornea, aphakia, and microphthalmia were identified in the village, rendering a disease prevalence of 2.52 cases per 1,000 habitants (1 in 397). The FOXE3 homozygous mutation was identified in all 17 affected subjects who consented to molecular analysis. Haplotype analysis indicated that the mutation arose 5.0-6.5 generations ago (approximately 106-138 years). Among the 405 unaffected villagers who were genotyped, ten heterozygote carriers were identified, yielding a population carrier frequency of approximately 1 in 40 and a predicted incidence of affected of 1 in 6,400 based on random marriages between two carriers in the village. This study demonstrates that a cluster of patients with sclerocornea, aphakia, and microphthalmia in a small Mexican village is due to a FOXE3 p.Y98H founder mutation that arose in the village just over a century ago at a time when a population migrated from a nearby village because of land disputes. The actual disease incidence is higher than the calculated predicted value and suggests non-random marriages (i.e., consanguinity) within the

  7. Youth in Dead End

    Directory of Open Access Journals (Sweden)

    Duygu TANRIKULU

    2011-01-01

    Full Text Available The primary factor to ensure economic and social development and also to build a healthy society is the education system which plays a significant role in human capital formation and shapes the social structure and its outputs. In this context, there are some risks threatening the youth that is trying to position itself on the education-employment line and some critical areas in need of national policy intervention as well. Hence, by analyzing indicators on education and labor force, this study aims to reveal the amount of youth under risk and to identify these critical areas, while targeting to highlight the urgent need for policy development focusing on youth in dead end. Within the study, it is emphasized that the education system causes youth to face with the problems of access and quality, and that there is a significant amount of youth not in education and employment, while underlining the necessity of bringing especially this inactive youth in economy in addition to equipping with required qualifications for their active participation in social life. Thus, in order to hinder human capital loss additionally, there is policy need in two directions, as focusing on the education system to prevent new hopeless generations on the one hand, and on the inclusion of the disadvantaged youth on the other.

  8. Isolation of three B-box zinc finger proteins that interact with STF1 and COP1 defines a HY5/COP1 interaction network involved in light control of development in soybean.

    Science.gov (United States)

    Shin, Su Young; Kim, Seong Hee; Kim, Hye Jin; Jeon, Su Jeong; Sim, Soon Ae; Ryu, Gyeong Ryul; Yoo, Cheol Min; Cheong, Yong Hwa; Hong, Jong Chan

    2016-09-23

    LONG HYPOCOTYL5 (HY5) and STF1 (Soybean TGACG-motif binding Factor 1) are two related bZIP transcription factors that play a positive role in photomorphogenesis and hormonal signaling. In this study, we compared full length STF1 and truncated STF1 overexpression lines and found that the C-terminal 133 amino acids (194-306) possess all the HY5-like function in Arabidopsis. The STF1-DC1 mutant (1-306), with a 20 amino acid deletion at the carboxy terminus, failed to complement the hy5 mutant phenotype, which suggests an intact C-terminus is required for STF1 function. To understand the role of the C-terminal domain in photomorphogenesis we used a yeast two-hybrid screen to isolate proteins that bind to the STF1 C-terminus. We isolated three soybean cDNAs encoding the zinc-finger proteins GmSTO, GmSTH, and GmSTH2, which interact with STF1. These proteins belong to a family of B-box zinc finger proteins that include Arabidopsis SALT TOLERANCE (STO) and STO HOMOLOG (STH) and STH2, which play a role in light-dependent development and gene expression. The C-terminal 63 amino acids of STF1, containing a leucine zipper and the two N-terminal B-boxes, contains the domain involved in interactions between STF1 and GmSTO. In addition, we identified an interaction between soybean COP1 (GmCOP1) and GmSTO and GmSTH, as well as STF1, which strongly suggests the presence of a similar regulatory circuit for light signaling in soybean as in Arabidopsis. This study shows that photomorphogenic control requires complex molecular interactions among several different classes of transcription factors such as bZIP, B-box factors, and COP1, a ubiquitin ligase. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Malaria's deadly grip

    DEFF Research Database (Denmark)

    Smith, Joseph D; Rowe, J Alexandra; Higgins, Matthew K

    2013-01-01

    Cytoadhesion of Plasmodium falciparum-infected erythrocytes to host microvasculature is a key virulence determinant. Parasite binding is mediated by a large family of clonally variant adhesion proteins, termed P. falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by var genes and expressed...

  10. Thinking outside the Box

    Science.gov (United States)

    Fanshawe, Simon; Sriskandarajah, Dhananjayan

    2010-01-01

    Britain is not only more diverse than ever before, but that diversity itself is growing more diverse. Britain's simplistic "tick-box" approach to identity is in danger of inhibiting the very equality it seeks to promote. To question the tick-box is not to accuse local authorities of "political correctness gone mad". The notion…

  11. ALUMINUM BOX BUNDLING PRESS

    Directory of Open Access Journals (Sweden)

    Iosif DUMITRESCU

    2015-05-01

    Full Text Available In municipal solid waste, aluminum is the main nonferrous metal, approximately 80- 85% of the total nonferrous metals. The income per ton gained from aluminum recuperation is 20 times higher than from glass, steel boxes or paper recuperation. The object of this paper is the design of a 300 kN press for aluminum box bundling.

  12. Precise measurement of dead time

    International Nuclear Information System (INIS)

    Schoenfeld, E.; Janssen, H.

    1994-01-01

    Four methods are discussed by which dead times of the non-extending type can be determined experimentally. Two methods using statistical pulses were improved by eliminating uncertainties due to counting statistics. However, it was concluded from a comparison of the four methods that those using periodical pulses are not only less time-consuming but are preferable if high-precision values are aimed at. A dead-time unit with quartz oscillator-based dead times of the non-extending type was tested using all of the four methods. Measurements within a period of three years indicated that the unit investigated here has subnanosecond stability for each of the adjusted dead-time values. (orig.)

  13. Anthrax, People and Dead Hippos

    Centers for Disease Control (CDC) Podcasts

    2017-11-07

    Epidemiologist, Dr. Melissa Marx, discuses anthrax deaths in people who ate dead hippos.  Created: 11/7/2017 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/7/2017.

  14. And the Dead Remain Behind

    Directory of Open Access Journals (Sweden)

    Peter Read

    2013-08-01

    Full Text Available In most cultures the dead and their living relatives are held in a dialogic relationship. The dead have made it clear, while living, what they expect from their descendants. The living, for their part, wish to honour the tombs of their ancestors; at the least, to keep the graves of the recent dead from disrepair. Despite the strictures, the living can fail their responsibilities, for example, by migration to foreign countries. The peripatetic Chinese are one of the few cultures able to overcome the dilemma of the wanderer or the exile. With the help of a priest, an Australian Chinese migrant may summon the soul of an ancestor from an Asian grave to a Melbourne temple, where the spirit, though removed from its earthly vessel, will rest and remain at peace. Amongst cultures in which such practices are not culturally appropriate, to fail to honour the family dead can be exquisitely painful. Violence is the cause of most failure.

  15. Climate change and dead zones.

    Science.gov (United States)

    Altieri, Andrew H; Gedan, Keryn B

    2015-04-01

    Estuaries and coastal seas provide valuable ecosystem services but are particularly vulnerable to the co-occurring threats of climate change and oxygen-depleted dead zones. We analyzed the severity of climate change predicted for existing dead zones, and found that 94% of dead zones are in regions that will experience at least a 2 °C temperature increase by the end of the century. We then reviewed how climate change will exacerbate hypoxic conditions through oceanographic, ecological, and physiological processes. We found evidence that suggests numerous climate variables including temperature, ocean acidification, sea-level rise, precipitation, wind, and storm patterns will affect dead zones, and that each of those factors has the potential to act through multiple pathways on both oxygen availability and ecological responses to hypoxia. Given the variety and strength of the mechanisms by which climate change exacerbates hypoxia, and the rates at which climate is changing, we posit that climate change variables are contributing to the dead zone epidemic by acting synergistically with one another and with recognized anthropogenic triggers of hypoxia including eutrophication. This suggests that a multidisciplinary, integrated approach that considers the full range of climate variables is needed to track and potentially reverse the spread of dead zones. © 2014 John Wiley & Sons Ltd.

  16. Molecular cloning and characterization of an F-box family gene CarF-box1 from chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Jia, Yuying; Gu, Hanyan; Wang, Xiansheng; Chen, Quanjia; Shi, Shubing; Zhang, Jusong; Ma, Lin; Zhang, Hua; Ma, Hao

    2012-03-01

    F-box protein family has been found to play important roles in plant development and abiotic stress responses via the ubiquitin pathway. In this study, an F-box gene CarF-box1 (for Cicer arietinum F-box gene 1, Genbank accession no. GU247510) was isolated based on a cDNA library constructed with chickpea seedling leaves treated by polyethylene glycol. CarF-box1 encoded a putative protein with 345 amino acids and contained no intron within genomic DNA sequence. CarF-box1 is a KFB-type F-box protein, having a conserved F-box domain in the N-terminus and a Kelch repeat domain in the C-terminus. CarF-box1 was localized in the nucleus. CarF-box1 exhibited organ-specific expression and showed different expression patterns during seed development and germination processes, especially strongly expressed in the blooming flowers. In the leaves, CarF-box1 could be significantly induced by drought stress and slightly induced by IAA treatment, while in the roots, CarF-box1 could be strongly induced by drought, salinity and methyl jasmonate stresses. Our results suggest that CarF-box1 encodes an F-box protein and may be involved in various plant developmental processes and abiotic stress responses.

  17. The mechanism by which TATA-box polymorphisms associated with human hereditary diseases influence interactions with the TATA-binding protein.

    Science.gov (United States)

    Drachkova, Irina; Savinkova, Ludmila; Arshinova, Tatyana; Ponomarenko, Mikhail; Peltek, Sergey; Kolchanov, Nikolay

    2014-05-01

    SNPs in ТАТА boxes are the cause of monogenic diseases, contribute to a large number of complex diseases, and have implications for human sensitivity to external and internal environmental signals. The aim of this work was to explore the kinetic characteristics of the formation of human ТВР complexes with ТАТА boxes, in which the SNPs are associated with β-thalassemias of diverse severity, immunosuppression, neurological disorders, and so on. It has for the first time been demonstrated, using an electrophoretic mobility shift assay, that TBP interacts with SNP-containing ТАТА boxes with a significant (8-36-fold) decrease in TBP/ТАТА association rate constant (ka ) as compared with that in healthy people, a smaller decrease in dissociation rate constant (kd ) and changes in the half-lives of TBP/ТАТА complexes. Carriers of the -24G allele (rs 1800202T>G) in the TATA box of the triosephosphate isomerase gene promoter, associated with neurological and muscular disorders, were observed to have a 36-fold decrease in TBP/TATA association rate constant that are consistent with TPI deficiency shown for patients who carry this defective allele. The kinetic characteristics of TBP/ТАТА complexes obtained suggest that, at a molecular level, hereditary diseases are largely caused by changes in TBP/ТАТА association rates and these changes have a bearing on disease severity. © 2014 WILEY PERIODICALS, INC.

  18. An attenuated herpes simplex virus type 1 (HSV1 encoding the HIV-1 Tat protein protects mice from a deadly mucosal HSV1 challenge.

    Directory of Open Access Journals (Sweden)

    Mariaconcetta Sicurella

    Full Text Available Herpes simplex virus types 1 and 2 (HSV1 and HSV2 are common infectious agents in both industrialized and developing countries. They cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. Current treatment for HSV relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. Therefore, prevention rather than treatment of HSV infections has long been an area of intense research, but thus far effective anti-HSV vaccines still remain elusive. One of the key hurdles to overcome in anti-HSV vaccine development is the identification and effective use of strategies that promote the emergence of Th1-type immune responses against a wide range of epitopes involved in the control of viral replication. Since the HIV1 Tat protein has several immunomodulatory activities and increases CTL recognition of dominant and subdominant epitopes of heterologous antigens, we generated and assayed a recombinant attenuated replication-competent HSV1 vector containing the tat gene (HSV1-Tat. In this proof-of-concept study we show that immunization with this vector conferred protection in 100% of mice challenged intravaginally with a lethal dose of wild-type HSV1. We demonstrate that the presence of Tat within the recombinant virus increased and broadened Th1-like and CTL responses against HSV-derived T-cell epitopes and elicited in most immunized mice detectable IgG responses. In sharp contrast, a similarly attenuated HSV1 recombinant vector without Tat (HSV1-LacZ, induced low and different T cell responses, no measurable antibody responses and did not protect mice against the wild-type HSV1 challenge. These findings strongly suggest that recombinant HSV1 vectors expressing Tat merit further investigation for their potential to prevent and/or contain HSV1

  19. Dead sea asphalts: historical aspects

    Energy Technology Data Exchange (ETDEWEB)

    Nissenbaum, A.

    1978-05-01

    Asphalts are present in the Dead Sea basin in three forms: (1) huge blocks, up to 100 tons in weight, composed of extremely pure (>99.99%) solid asphalt occasionally found floating on the lake, (2) veins, seepages, and cavity and fissure fillings in Lower Cretaceous to Holocene rocks, and (3) ozocerite veins on the eastern shore of the lake. Dead Sea asphalts probably have been documented over a longer period of time than any other hydrocarbon deposit--from antiquity to the 19th century. Major uses of asphalt from the Dead Sea have been as an ingredient in the embalming process, for medicinal purposes, for fumigation, and for agriculture. The first known war for control of a hydrocarbon deposit was in the Dead Sea area in 312 B.C. between the Seleucid Syrians and the Nabatean Arabs who lived around the lake. Surface manifestations of asphalt are linked closely to tectonic activity. In the lake itself, the asphalt is associated with diapirs During certain historic periods, tectonic and diapiric activity caused frequent liberation to the Dead Sea surface of semiliquid asphalt associated with large amounts of hydrogen sulfide gas. When the tectonic activity was attenuated, as in the 19th and 20th centuries, the rate of asphalt seepage to the bottom sediments of the Dead Sea was much slower and the asphalt solidified on the lake bottom. The release of asphalt to the surface became much more sporadic, and may have resulted in part from earthquakes. Thus, future asphalt prospecting in the Dead Sea area should be conducted along the boundaries of diapirs or their associated faults.

  20. Glove box shield

    Science.gov (United States)

    Brackenbush, L.W.; Hoenes, G.R.

    A shield for a glove box housing radioactive material is comprised of spaced apart clamping members which maintain three overlapping flaps in place therebetween. There is a central flap and two side flaps, the side flaps overlapping at the interior edges thereof and the central flap extending past the intersection of the side flaps in order to insure that the shield is always closed when the user wthdraws his hand from the glove box. Lead loaded neoprene rubber is the preferred material for the three flaps, the extent of lead loading depending upon the radiation levels within the glove box.

  1. Ranavirus infection of free-ranging and captive box turtles and tortoises in the United States.

    Science.gov (United States)

    Johnson, April J; Pessier, Allan P; Wellehan, James F X; Childress, April; Norton, Terry M; Stedman, Nancy L; Bloom, David C; Belzer, William; Titus, Valorie R; Wagner, Robert; Brooks, Jason W; Spratt, Jeffrey; Jacobson, Elliott R

    2008-10-01

    Iridoviruses of the genus Ranavirus are well known for causing mass mortality events of fish and amphibians with sporadic reports of infection in reptiles. This article describes five instances of Ranavirus infection in chelonians between 2003 and 2005 in Georgia, Florida, New York, and Pennsylvania, USA. Affected species included captive Burmese star tortoises (Geochelone platynota), a free-ranging gopher tortoise (Gopherus polyphemus), free-ranging eastern box turtles (Terrapene carolina carolina), and a Florida box turtle (Terrepene carolina bauri). Evidence for Ranavirus infection was also found in archived material from previously unexplained mass mortality events of eastern box turtles from Georgia in 1991 and from Texas in 1998. Consistent lesions in affected animals included necrotizing stomatitis and/or esophagitis, fibrinous and necrotizing splenitis, and multicentric fibrinoid vasculitis. Intracytoplasmic inclusion bodies were rarely observed in affected tissues. A portion of the major capsid protein (MCP) gene was sequenced from each case in 2003-2005 and found to be identical to each other and to Frog virus 3 (FV3) across 420 base pairs. Ranavirus infections were also documented in sympatric species of amphibians at two locations with infected chelonians. The fragment profiles of HindIII-digested whole genomic DNA of Ranavirus, isolated from a dead Burmese star tortoise and a southern leopard frog (Rana utricularia) found nearby, were similar. The box turtle isolate had a low molecular weight fragment that was not seen in the digestion profiles for the other isolates. These results suggest that certain amphibians and chelonians are infected with a similar virus and that different viruses exist among different chelonians. Amphibians may serve as a reservoir host for susceptible chelonians. This report also demonstrated that significant disease associated with Ranavirus infections are likely more widespread in chelonians than previously suspected.

  2. Voice box (image)

    Science.gov (United States)

    The larynx, or voice box, is located in the neck and performs several important functions in the body. The larynx is involved in swallowing, breathing, and voice production. Sound is produced when the air which ...

  3. The POWHEG-BOX

    OpenAIRE

    Oleari, Carlo

    2010-01-01

    We review the key features of POWHEG, a method for interfacing parton-shower Monte Carlo generators to fixed next-to-leading order QCD computations. We describe a recently introduced framework, the POWHEG-BOX, that allows the automatic POWHEG implementation of any given NLO calculation. We present a few results for Higgs boson production via vector boson fusion and Z + 1 jet production, both processes available in the POWHEG-BOX.

  4. Boxes and Shelves

    OpenAIRE

    Hughes, Dean

    2008-01-01

    The Boxes and Shelves series from 2008 are are all made from the backing card from discarded writing pads. Boxes and Shelves extended my investigation of quotidian materials and their relationship to the origins of creative toil. Since 1996 my research has sought to identify and locate instances where the 'unmeasurable' meets the measurable. I have consistently employed a range of utilitarian materials such as bus seats, bus tickets, puddles, A4 writing paper, to present a series of 'problem ...

  5. Using FRET to Measure the Angle at Which a Protein Bends DNA: TBP Binding a TATA Box as a Model System

    Science.gov (United States)

    Kugel, Jennifer F.

    2008-01-01

    An undergraduate biochemistry laboratory experiment that will teach the technique of fluorescence resonance energy transfer (FRET) while analyzing protein-induced DNA bending is described. The experiment uses the protein TATA binding protein (TBP), which is a general transcription factor that recognizes and binds specific DNA sequences known as…

  6. The Right to be Dead

    DEFF Research Database (Denmark)

    Sabra, Jakob Borrits; Troyer, John Eric

    2018-01-01

    -mortem handling of their exponentially increased digital data. The European Union Court of Justice ruled that a person has a Right to be Forgotten on the world wide web. The Future Cemetery asks: Does a person have the Right to be Dead on this information superhighway? Our essay pursues these specific lines...

  7. Channel box compression device

    International Nuclear Information System (INIS)

    Nakamizo, Hiroshi; Tanaka, Yuki.

    1996-01-01

    The device of the present invention reduces the volume of spent fuel channel boxes of power plant facilities to eliminate secondary wastes, suppress generation of radiation sources and improve storage space efficiency. The device has a box-like shape. A support frame is disposed on the lateral side of the box for supporting spent channel boxes. A horizontal transferring unit and a vertical transferring compression unit driven by a driving mechanism are disposed in the support frame. Further, the compression unit may have a rotational compression roller so as to move freely in the transferring unit. In addition, the transferring unit and the driving mechanism may be disposed outside of pool water. With such a constitution, since spent channel boxes are compressed and bent by horizontal movement of the transferring unit and the vertical movement of the compression unit, no cut pieces or cut powders are generated. Further, if the transferring unit and the driving mechanism are disposed outside of the pool water, it is not necessary to make them waterproof, which facilitates the maintenance. (I.S.)

  8. The BOXES Methodology Black Box Dynamic Control

    CERN Document Server

    Russell, David W

    2012-01-01

    Robust control mechanisms customarily require knowledge of the system’s describing equations which may be of the high order differential type.  In order to produce these equations, mathematical models can often be derived and correlated with measured dynamic behavior.  There are two flaws in this approach one is the level of inexactness introduced by linearizations and the other when no model is apparent.  Several years ago a new genre of control systems came to light that are much less dependent on differential models such as fuzzy logic and genetic algorithms. Both of these soft computing solutions require quite considerable a priori system knowledge to create a control scheme and sometimes complicated training program before they can be implemented in a real world dynamic system. Michie and Chambers’ BOXES methodology created a black box system that was designed to control a mechanically unstable system with very little a priori system knowledge, linearization or approximation.  All the method need...

  9. A sugar beet chlorophyll a/b binding protein promoter void of G-box like elements confers strong and leaf specific reporter gene expression in transgenic sugar beet

    Directory of Open Access Journals (Sweden)

    Kloos Dorothee U

    2004-12-01

    Full Text Available Abstract Background Modification of leaf traits in sugar beet requires a strong leaf specific promoter. With such a promoter, expression in taproots can be avoided which may otherwise take away available energy resources for sugar accumulation. Results Suppression Subtractive Hybridization (SSH was utilized to generate an enriched and equalized cDNA library for leaf expressed genes from sugar beet. Fourteen cDNA fragments corresponding to thirteen different genes were isolated. Northern blot analysis indicates the desired tissue specificity of these genes. The promoters for two chlorophyll a/b binding protein genes (Bvcab11 and Bvcab12 were isolated, linked to reporter genes, and transformed into sugar beet using promoter reporter gene fusions. Transient and transgenic analysis indicate that both promoters direct leaf specific gene expression. A bioinformatic analysis revealed that the Bvcab11 promoter is void of G-box like regulatory elements with a palindromic ACGT core sequence. The data indicate that the presence of a G-box element is not a prerequisite for leaf specific and light induced gene expression in sugar beet. Conclusions This work shows that SSH can be successfully employed for the identification and subsequent isolation of tissue specific sugar beet promoters. These promoters are shown to drive strong leaf specific gene expression in transgenic sugar beet. The application of these promoters for expressing resistance improving genes against foliar diseases is discussed.

  10. XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.

    Science.gov (United States)

    Jiang, Meng; Yu, Shu; Yu, Zhui; Sheng, Huaxin; Li, Ying; Liu, Shuai; Warner, David S; Paschen, Wulf; Yang, Wei

    2017-06-01

    Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke. To restore endoplasmic reticulum function impaired by stress, the unfolded protein response is activated. A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation). Stroke impairs endoplasmic reticulum function, which activates unfolded protein response. The rationale of this study was to explore the potentials of the IRE1/XBP1/O-GlcNAc axis as a target for neuroprotection in ischemic stroke. Mice with Xbp1 loss and gain of function in neurons were generated. Stroke was induced by transient or permanent occlusion of the middle cerebral artery in young and aged mice. Thiamet-G was used to increase O-GlcNAcylation. Deletion of Xbp1 worsened outcome after transient and permanent middle cerebral artery occlusion. After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent. This activation of O-GlcNAcylation was impaired in aged mice. Pharmacological increase of O-GlcNAcylation before or after stroke improved outcome in both young and aged mice. Our study indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome. O-GlcNAcylation is a prosurvival pathway that is activated in the stroke penumbra in young mice but impaired in aged mice. Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains. © 2017 American Heart Association, Inc.

  11. Opto-Box

    CERN Document Server

    Bertsche, David; The ATLAS collaboration; Welch, Steven; Smith, Dale Shane; Che, Siinn; Gan, K.K.; Boyd, George Russell Jr

    2015-01-01

    The opto-box is a custom mini-crate for housing optical modules, which process and transfer optoelectronic data. The system tightly integrates electrical, mechanical, and thermal functionality into a small package of size 35x10x8 cm^3. Special attention was given to ensure proper shielding, grounding, cooling, high reliability, and environmental tolerance. The custom modules, which incorporate Application Specific Integrated Circuits (ASICs), were developed through a cycle of rigorous testing and redesign. In total, fourteen opto-boxes have been installed and loaded with modules on the ATLAS detector. They are currently in operation as part of the LHC run 2 data read-out chain.

  12. Identifying location by dead reckoning and external cues.

    Science.gov (United States)

    Georgakopoulos, J; Etienne, A S

    1994-02-01

    Golden hamsters can orient towards specific points in their environment using location- based visual cues and/or dead reckoning based on vestibular and proprioceptive signals. The relative weight of these different kinds of information was investigated in an apparatus consisting of three identical, square compartments joined by tunnels, with the subject's own nest box at one end. Each compartment contained a feeding site and a weak light spot, the relation between the feeding site and the light spot being different in the three compartments. The animals were trained to hoard food in succession from the three feeding locations, in darkness. During test trials, the light spots were either suppressed or moved to new locations, thus being set in conflict with other kinds of spatial information. In the majority of trials, the subjects proceeded fairly directly to the feeding places, independently of the presence and position of the light spots. This performance may be explained through rote motor learning, which may be initiated with respect to tactile cues previously associated to the goal. However, more flexible, indirect trajectories towards the goal suggest that the subjects kept track of their location within the test space and therefore depended simultaneously on dead reckoning and a map. A control experiment in which the goals were moved along with the visual cues excluded the use of olfactory cues from the food source and confirmed the role of dead reckoning. Copyright © 1994. Published by Elsevier B.V.

  13. Is Schrödinger's cat dead oa alive?

    Directory of Open Access Journals (Sweden)

    Wojciech Grygiel

    2005-12-01

    Full Text Available The Schrödinger's Cat paradox was proposed in 1935 by Edwin Schrodinger, one of the founders of quantum mechanics, as an attempt to visualize the macroscopic realization of a quantum superposition state. A cat is placed in a sealed box together with a vial of poison. A two-state particle (e.g. an electron is sent into a detector in the box resulting either in a broken or an intact vial and a dead or live cat, respectively. The main problem consists in whether the superposition state of a microscopic particle can be transferred upon the macroscopic cat, that is, whether the cat can exist in a superposition state, being simultaneously dead and alive. Since the standard Copenhagen interpretation is unable to assign any reality to the quantum superposition state, the paradox finds no resolution within the regime of this interpretation. Von Neumann's insistence on the uniform treatment of both microscopic (quantum and macroscopic (classical objects according to the laws of quantum mechanics provides a more consistent framework for the resolution of the paradox. In particular, the discovery of the phenomenon of decoherence, whereby the disappearance of the quantum interferences at the macro level is accounted for, suggests the onset of an extremely efficient interference relaxation process (10-23 s upon the interaction of the two state particle with the detector. As a result, Schrodinger's cat can exist macroscopically either as dead or alive and never as a combination of both. Decoherence not only aids the resolution of the Schrodinger's Cat paradox but also sheds light upon the mechanisms by which the macro-world emerges from the microscopic quantum realm.

  14. Structure and biochemical function of a prototypical Arabidopsis U-box domain

    DEFF Research Database (Denmark)

    Andersen, Pernille; Kragelund, Birthe B; Olsen, Addie N

    2004-01-01

    U-box proteins, as well as other proteins involved in regulated protein degradation, are apparently over-represented in Arabidopsis compared with other model eukaryotes. The Arabidopsis protein AtPUB14 contains a typical U-box domain followed by an Armadillo repeat region, a domain organization t...

  15. 7 CFR 322.29 - Dead bees.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Dead bees. 322.29 Section 322.29 Agriculture..., DEPARTMENT OF AGRICULTURE BEES, BEEKEEPING BYPRODUCTS, AND BEEKEEPING EQUIPMENT Importation and Transit of Restricted Articles § 322.29 Dead bees. (a) Dead bees imported into or transiting the United States must be...

  16. Teaching with Box Tops.

    Science.gov (United States)

    Raiser, Lynne; D'Zamko, Mary Elizabeth

    1984-01-01

    Using environmental materials (such as the phone book and placemats from fast food restaurants) can be a motivating way to teach learning disabled students skills and concepts, as shown in an approach to reading, math, science and nutrition, and social studies instruction using a JELL-O brand gelatin box. (CL)

  17. Glove box posting system

    International Nuclear Information System (INIS)

    McIntosh, A.E.

    1981-01-01

    A system for posting objects into closed containers, such as glove boxes, is described in which the bag used, preferably made of plastic, does not have to be fitted and sealed by the operator during each posting operation. (U.K.)

  18. Many-box locality

    Science.gov (United States)

    Zhou, Yuqian; Cai, Yu; Bancal, Jean-Daniel; Gao, Fei; Scarani, Valerio

    2017-11-01

    There is an ongoing search for a physical or operational definition for quantum mechanics. Several informational principles have been proposed which are satisfied by a theory less restrictive than quantum mechanics. Here, we introduce the principle of "many-box locality," which is a refined version of the previously proposed "macroscopic locality." These principles are based on coarse graining the statistics of several copies of a given box. The set of behaviors satisfying many-box locality for N boxes is denoted LNM B. We study these sets in the bipartite scenario with two binary measurements, in relation with the sets Q and Q1 +A B of quantum and "almost quantum" correlations, respectively. We find that the LNM B sets are, in general, not convex. For unbiased marginals, by working in the Fourier space we can prove analytically that LNM B⊈Q for any finite N , while L∞M B=Q . Then, with suitably developed numerical tools, we find an example of a point that belongs to L16M B but not to Q1 +A B. Among the problems that remain open is whether Q ⊂L∞M B .

  19. Mystery Box Marvels

    Science.gov (United States)

    Santos, Joel; Centurio, Tina

    2012-01-01

    What happens in the first week of school could very well set the stage for the rest of the school year. Setting high standards for science activities based in inquiry can start on the first day of science class and develop as the year unfolds. With the use of simple, readily available, inexpensive materials, an efficient mystery box lesson can be…

  20. IN-A-BOX

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 7; Issue 2. Claude Elwood Shannon. Priti Shankar. Article-in-a-Box Volume 7 Issue 2 February 2002 pp 2-3 ... Author Affiliations. Priti Shankar1. Department of Computer Science & Automation, Indian Institute of Science, Bangalore 560 012, India.

  1. IN-A-BOX

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 6; Issue 12. Vikram A Sarabhai. Mrinalini Sarabhai. Article-in-a-Box Volume 6 Issue 12 December 2001 pp 5-7. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/006/12/0005-0007. Author Affiliations. Mrinalini ...

  2. Global risk of deadly heat

    Science.gov (United States)

    Mora, Camilo; Dousset, Bénédicte; Caldwell, Iain R.; Powell, Farrah E.; Geronimo, Rollan C.; Bielecki, Coral R.; Counsell, Chelsie W. W.; Dietrich, Bonnie S.; Johnston, Emily T.; Louis, Leo V.; Lucas, Matthew P.; McKenzie, Marie M.; Shea, Alessandra G.; Tseng, Han; Giambelluca, Thomas W.; Leon, Lisa R.; Hawkins, Ed; Trauernicht, Clay

    2017-07-01

    Climate change can increase the risk of conditions that exceed human thermoregulatory capacity. Although numerous studies report increased mortality associated with extreme heat events, quantifying the global risk of heat-related mortality remains challenging due to a lack of comparable data on heat-related deaths. Here we conducted a global analysis of documented lethal heat events to identify the climatic conditions associated with human death and then quantified the current and projected occurrence of such deadly climatic conditions worldwide. We reviewed papers published between 1980 and 2014, and found 783 cases of excess human mortality associated with heat from 164 cities in 36 countries. Based on the climatic conditions of those lethal heat events, we identified a global threshold beyond which daily mean surface air temperature and relative humidity become deadly. Around 30% of the world's population is currently exposed to climatic conditions exceeding this deadly threshold for at least 20 days a year. By 2100, this percentage is projected to increase to ~48% under a scenario with drastic reductions of greenhouse gas emissions and ~74% under a scenario of growing emissions. An increasing threat to human life from excess heat now seems almost inevitable, but will be greatly aggravated if greenhouse gases are not considerably reduced.

  3. Electronic fingerprinting of the dead.

    Science.gov (United States)

    Rutty, G N; Stringer, K; Turk, E E

    2008-01-01

    To date, a number of methods exist for the capture of fingerprints from cadavers that can then be used in isolation as a primary method for the identification of the dead. We report the use of a handheld, mobile wireless unit used in conjunction with a personal digital assistant (PDA) device for the capture of fingerprints from the dead. We also consider a handheld single-digit fingerprint scanner that utilises a USB laptop connection for the electronic capture of cadaveric fingerprints. Both are single-operator units that, if ridge detail is preserved, can collect a 10-set of finger pad prints in approximately 45 and 90 s, respectively. We present our observations on the restrictions as to when such devices can be used with cadavers. We do, however, illustrate that the images are of sufficient quality to allow positive identification from finger pad prints of the dead. With the development of mobile, handheld, biometric, PDA-based units for the police, we hypothesize that, under certain circumstances, devices such as these could be used for the accelerated acquisition of fingerprint identification data with the potential for rapid near-patient identification in the future.

  4. Microglial Amyloid-β1-40 Phagocytosis Dysfunction Is Caused by High-Mobility Group Box Protein-1: Implications for the Pathological Progression of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Kazuyuki Takata

    2012-01-01

    Full Text Available In Alzheimer disease (AD patient brains, the accumulation of amyloid-β (Aβ peptides is associated with activated microglia. Aβ is derived from the amyloid precursor protein; two major forms of Aβ, that is, Aβ1-40 (Aβ40 and Aβ1-42 (Aβ42, exist. We previously reported that rat microglia phagocytose Aβ42, and high mobility group box protein 1 (HMGB1, a chromosomal protein, inhibits phagocytosis. In the present study, we investigated the effects of exogenous HMGB1 on rat microglial Aβ40 phagocytosis. In the presence of exogenous HMGB1, Aβ40 markedly increased in microglial cytoplasm, and the reduction of extracellular Aβ40 was inhibited. During this period, HMGB1 was colocalized with Aβ40 in the cytoplasm. Furthermore, exogenous HMGB1 inhibited the degradation of Aβ40 induced by the rat microglial cytosolic fraction. Thus, extracellular HMGB1 may internalize with Aβ40 in the microglial cytoplasm and inhibit Aβ40 degradation by microglia. This may subsequently delay Aβ40 clearance. We further confirmed that in AD brains, the parts of senile plaques surrounded by activated microglia are composed of Aβ40, and extracellular HMGB1 is deposited on these plaques. Taken together, microglial Aβ phagocytosis dysfunction may be caused by HMGB1 that accumulates extracellularly on Aβ plaques, and it may be critically involved in the pathological progression of AD.

  5. Immunoreactivity to the pre-core box antibody shows that most glycine-rich beta-proteins accumulate in lepidosaurian beta-layer and in the corneous layer of crocodilian and turtle epidermis.

    Science.gov (United States)

    Alibardi, L

    2014-02-01

    The differentiation of the corneous layers of reptilian epidermis has been analyzed by ultrastructural immunocytochemistry using specific antibodies against the conserved pre-core box region of their keratin-associated beta-proteins (KAbetaPs, formerly indicated as beta-keratins) and silver-intensification. The epitope analysis in the sequences of different reptilian KAbetaPs indicates that this antibody recognizes mainly glycine-rich beta-proteins in lizards and snakes. The immunoreactivity of the beta-layer of the tuatara to this antibody also suggests that a similar epitope is present in beta-proteins of this relict species. In crocodilians the antibody recognizes glycine-rich beta-proteins, so far representing all the known crocodilian KAbetaPs. In hard-shelled turtle the antibody labels mainly type 1 KAbetaPs that represent most types found in this turtle. The antibody does not label the corneous layer of the soft-shelled turtle that contains exclusively type 2 KAbetaPs, with a low identity to the epitope recognized by the antibody. The prevalent labeling of the beta-layers in lepidosaurian epidermis and of the corneous layer in turtle and crocodilian epidermis suggest that this antibody is mainly directed toward KAbetaPs rich in glycine. The latter are main constituents of the corneous layer in turtles and crocodilians and of the beta-layer in lizards, snakes and the tuatara. These proteins are largely responsible for the inflexibility, mechanical resistance, chromophobicity and relative hydrophobicity of the reptilian corneous layer. Copyright © 2013. Published by Elsevier Ltd.

  6. Opto-Box

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00377159; The ATLAS collaboration

    2015-01-01

    The opto-box is a custom mini-crate for housing optical modules, which process and transfer optoelectronic data. Many novel solutions were developed for the custom design and manufacturing. The system tightly integrates electrical, mechanical, and thermal functionality into a small package of size 35x10x8 cm$^{3}$. Special attention was given to ensure proper shielding, grounding, cooling, high reliability, and environmental tolerance. The custom modules, which incorporate Application Specific Integrated Circuits (ASICs), were developed through a cycle of rigorous testing and redesign. In total, fourteen opto-boxes have been installed and loaded with modules on the ATLAS detector. They are currently in operation as part of the LHC run 2 data read-out chain.

  7. Localization and Differential Expression of the Krüppel-Associated Box Zinc Finger Proteins 1 and 54 in Early Mouse Development

    DEFF Research Database (Denmark)

    Albertsen, Maria; Teperek, Marta; Elholm, Grethe

    2010-01-01

    -fused reporter gene into zygotes demonstrated the intracellular distribution of ZFP1-green fluorescent protein (GFP) and ZFP54-GFP colocalized with a DNA marker in the two-cell embryo. The KRAB domain was essential to colocalize with DNA, and deletion of the KRAB domain in ZFP1-GFP and ZFP54-GFP localized...

  8. Boxed Permutation Pattern Matching

    DEFF Research Database (Denmark)

    Amit, Mika; Bille, Philip; Cording, Patrick Hagge

    2016-01-01

    the goal is to only find the boxed subsequences of T that are order-isomorphic to P. This problem was introduced by Bruner and Lackner who showed that it can be solved in O(n3) time. Cho et al. [CPM 2015] gave an O(n2m) time algorithm and improved it to O(n2 logm). In this paper we present a solution...

  9. The Box Method

    DEFF Research Database (Denmark)

    Nielsen, Peter Vilhelm

    The velocity level in a room ventilated by jet ventilation is strongly influenced by the supply conditions. The momentum flow in the supply jets controls the air movement in the room and, therefore, it is very important that the inlet conditions and the numerical method can generate a satisfactor...... description of this momentum flow. The Box Method is a practical method for the description of an Air Terminal Device which will save grid points and ensure the right level of the momentum flow....

  10. Are Brain Dead Individuals Dead? Grounds for Reasonable Doubt.

    Science.gov (United States)

    Brugger, E Christian

    2016-06-01

    According to the biological definition of death, a human body that has not lost the capacity to holistically organize itself is the body of a living human individual. Reasonable doubt against the conclusion that it has lost the capacity exists when the body appears to express it and no evidence to the contrary is sufficient to rule out reasonable doubt against the conclusion that the apparent expression is a true expression (i.e., when the conclusion that what appears to be holistic organization is in fact holistic organization remains a reasonable explanatory hypothesis in light of the best evidence to the contrary). This essay argues that the evidence and arguments against the conclusion that the signs of complex bodily integration exhibited in ventilated brain dead bodies are true expressions of somatic integration are unpersuasive; that is, they are not adequate to exclude reasonable doubt against the conclusion that BD bodies are dead. Since we should not treat as corpses what for all we know might be living human beings, it follows that we have an obligation to treat BD individuals as if they were living human beings. © The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Insights into the quality of DnaA boxes and their cooperativity

    DEFF Research Database (Denmark)

    Hansen, Flemming G.; Christensen, Bjarke Bak; Nielsen, Christina Bang

    2006-01-01

    Plasmids carrying the mioC promoter region with its two DnaA boxes are as efficient in titration of DnaA protein as plasmids carrying a replicationinactivated oriC region with its five DnaA boxes. The two DnaA boxes upstream of the mioC promoter were mutated in various ways to study the cooperati......Plasmids carrying the mioC promoter region with its two DnaA boxes are as efficient in titration of DnaA protein as plasmids carrying a replicationinactivated oriC region with its five DnaA boxes. The two DnaA boxes upstream of the mioC promoter were mutated in various ways to study...... the cooperativity between the DnaA boxes, and to study in vivo the in vitrodefined 9mer DnaA box consensus sequence TTA/TTNCACA). The quality and cooperativity of the DnaA oxes were determined in two complementary ways: as titration of DnaA protein leading to derepression of the dnaA promoter, and as repression...... of the mioC promoter caused by the DnaA protein binding to the DnaA boxes. Titration of DnaA protein correlated with repression of the mioC promoter. The level of titration and repression with the normal promoter-proximal box (TTTTCCACA) depends strongly on the presence and the quality of a DnaA box...

  12. Apoptotic Response through a High Mobility Box 1 Protein-Dependent Mechanism in LPS/GalN-Induced Mouse Liver Failure and Glycyrrhizin-Mediated Inhibition

    Science.gov (United States)

    Kuroda, Noriyuki; Inoue, Kouji; Ikeda, Tadayuki; Hara, Yaiko; Wake, Kenjiro; Sato, Tetsuji

    2014-01-01

    HMGB1 is a nuclear component involved in nucleosome stabilization and transcription regulation, but extracellularly it is able to serve as a potential late mediator of lethality. In the present study, we explored inflammation-promoting activity of HMGB1 and blockade of extracellular release of HMGB1 by glycyrrhizin (GL) in LPS/GalN-triggered mouse liver injury. At 1 to 10 h after LPS/GalN-treatment, mice were anesthetized to collect blood from heart puncture, and serum transaminase and HMGB1 were evaluated. Administration of LPS/GalN precipitated tissue injury associated with time-dependent alteration in HMGB1 serum levels. At 8 h nuclear immunoreactive products were remarkably reduced and extracellular HMGB1 expression was found exclusively in the pericentral foci. The treatment with GL significantly down-regulated the serum levels of ALT, AST, and HMGB1 in addition to the strong inhibition of tissue injury and extracellular immunoreactivity to HMGB1 and to acetylated-lysine. Furthermore, GL brought about a significant decrease in the number of apoptotic hepatocytes labeled with TUNEL-method. On the basis of these results, three apoptosis-associated genes were identified with microarray analysis and real-time PCR. The ChIP-assay revealed the binding of HMGB1 protein to Gsto1 promoter sequence in LPS/GalN-treated mice and the remarkable decrease in combined HMGB1 protein by GL. The current findings claim that a single injection of LPS/GalN might stimulate apoptosis of hepatocytes through the binding of HMGB1 protein to Gsto1 promoter region and that GL-treatment might prevent the apoptosis and inflammatory infiltrates caused with LPS/GalN-injection by disturbing the binding of HMGB1 protein to Gsto1 promoter sequence. PMID:24690901

  13. Phytoplasma effector SAP54 hijacks plant reproduction by degrading MADS-box proteins and promotes insect colonization in a RAD23-dependent manner.

    Directory of Open Access Journals (Sweden)

    Allyson M MacLean

    2014-04-01

    Full Text Available Pathogens that rely upon multiple hosts to complete their life cycles often modify behavior and development of these hosts to coerce them into improving pathogen fitness. However, few studies describe mechanisms underlying host coercion. In this study, we elucidate the mechanism by which an insect-transmitted pathogen of plants alters floral development to convert flowers into vegetative tissues. We find that phytoplasma produce a novel effector protein (SAP54 that interacts with members of the MADS-domain transcription factor (MTF family, including key regulators SEPALLATA3 and APETALA1, that occupy central positions in the regulation of floral development. SAP54 mediates degradation of MTFs by interacting with proteins of the RADIATION SENSITIVE23 (RAD23 family, eukaryotic proteins that shuttle substrates to the proteasome. Arabidopsis rad23 mutants do not show conversion of flowers into leaf-like tissues in the presence of SAP54 and during phytoplasma infection, emphasizing the importance of RAD23 to the activity of SAP54. Remarkably, plants with SAP54-induced leaf-like flowers are more attractive for colonization by phytoplasma leafhopper vectors and this colonization preference is dependent on RAD23. An effector that targets and suppresses flowering while simultaneously promoting insect herbivore colonization is unprecedented. Moreover, RAD23 proteins have, to our knowledge, no known roles in flower development, nor plant defence mechanisms against insects. Thus SAP54 generates a short circuit between two key pathways of the host to alter development, resulting in sterile plants, and promotes attractiveness of these plants to leafhopper vectors helping the obligate phytoplasmas reproduce and propagate (zombie plants.

  14. Dead time of dual detector tools

    International Nuclear Information System (INIS)

    Czubek, J.A.

    1994-01-01

    A theory of the dead time for the dual detector nuclear tool with the analogue signal transmission is given in the paper. At least two different times exist in such tools: the dead time of detectors (for final computation they assumed identical to each other) and the dead time of the signal transmission set-up. A method of two radioactive sources is proposed to measure these two different dead times. When the times used for measuring every countrate needed in the dead time determination algorithm are taken into account, the statistical accuracy of the dead time determination can be obtained. These estimations are performed by the computer simulation method. Two codes have been designed: DEADT2D (DEAD Time for 2 Detectors) and DEADT2DS (DEAD Time for 2 Detectors with Statistics). The first code calculates the dead time based on the recorded countrates only, the second is doing a 'simulation job' and provides information on the statistical distribution of the observed dead times. The theory and the numerical solutions were checked both by the simulation calculations and by the experiments performed with the ODSN-102 tool (the experiments were performed by T. Zorski). (Author)

  15. Outside the box

    International Nuclear Information System (INIS)

    Pichon, Max

    2011-01-01

    Full text: Queensland-based Hydrasyst wants to take its motto of 'Do more with less' into the greywater sector with a new water recycling and energy recovery technology launched in November, called The Grey Box. The company is initially targeting large industrial laundries as they are major generators of greywater and heavy energy users, but it has ambitions well beyond that. The average commercial laundry consumes 1-5ML of water a week, using about 16 litres for every 1kg of clothing washed. Hydrasyst director Stephen Balemi said The Grey Box can slash the volume by 80 per cent. While he was reluctant to disclose too much technical detail, he claimed it is the only technology serving the $1 billion a year laundry sector that combines microfiltration / ultrafiltration membrane technology and energy reduction components. The heart of the system is a ceramic hollow fibre membrane. Balemi said it produces higher filtrate quality than competitors, meaning the recycled water can be reused more often, and can process feed water of up to 70°C compared to typical ultrafiltration membranes that cap out at about 38°C. This means the recycled water can be reused at higher temperatures, with the heat in it recovered by a precise steam heater built into The Grey Box. “As an overall measure, it saves 80 per cent of the water that is processed and saves 20 per cent of the energy,” Balemi said. Four systems have already been installed, with one going into a large commercial laundry in south Queensland and another to AMP's state-of-the-art 6 Green Star building in Brisbane. “We can modify them slightly to suit the industry, depending on the quality of raw water they are trying to recycle and also depending on the size of the project,,” said Balemi. Where many organisations build systems to specification, The Grey Box is offered in three standard sizes: the HY20 (20kL per day, based on a 10 hour day), HY80 (80kL per day) and HY130 (130kL per day). They can

  16. Modification in amino acids of Dead Sea Scroll Parchments.

    Science.gov (United States)

    Sobel, H; Ajie, H

    1992-12-01

    Fragments of Dead Sea Scroll Parchments were extracted for collagen and subjected to amino acid analysis. In modern parchment samples, 90% or more of the protein could be extracted in hot aqueous solution as collagen. In the ancient specimens, 70% or less was extractable. The hot-solution insoluble material was analyzed for collagen. In the soluble extract, the quantity of tyrosine, histidine, and methionine was reduced. Dityrosine was detected. The need to extend such studies is discussed.

  17. Multi-output Model with Box-Jenkins Operators of Quadratic Indices for Prediction of Malaria and Cancer Inhibitors Targeting Ubiquitin- Proteasome Pathway (UPP) Proteins.

    Science.gov (United States)

    Casañola-Martin, Gerardo M; Le-Thi-Thu, Huong; Pérez-Giménez, Facundo; Marrero-Ponce, Yovani; Merino-Sanjuán, Matilde; Abad, Concepción; González-Díaz, Humberto

    2016-01-01

    The ubiquitin-proteasome pathway (UPP) is the primary degradation system of short-lived regulatory proteins. Cellular processes such as the cell cycle, signal transduction, gene expression, DNA repair and apoptosis are regulated by this UPP and dysfunctions in this system have important implications in the development of cancer, neurodegenerative, cardiac and other human pathologies. UPP seems also to be very important in the function of eukaryote cells of the human parasites like Plasmodium falciparum, the causal agent of the neglected disease Malaria. Hence, the UPP could be considered as an attractive target for the development of compounds with Anti-Malarial or Anti-cancer properties. Recent online databases like ChEMBL contains a larger quantity of information in terms of pharmacological assay protocols and compounds tested as UPP inhibitors under many different conditions. This large amount of data give new openings for the computer-aided identification of UPP inhibitors, but the intrinsic data diversity is an obstacle for the development of successful classifiers. To solve this problem here we used the Bob-Jenkins moving average operators and the atom-based quadratic molecular indices calculated with the software TOMOCOMD-CARDD (TC) to develop a quantitative model for the prediction of the multiple outputs in this complex dataset. Our multi-target model can predict results for drugs against 22 molecular or cellular targets of different organisms with accuracies above 70% in both training and validation sets.

  18. Identification and functional characterization of the goldfish (Carassius auratus L.) high mobility group box 1 (HMGB1) chromatin-binding protein.

    Science.gov (United States)

    Xie, Jiasong; Hodgkinson, Jordan W; Li, Chao; Kovacevic, Nikolina; Belosevic, Miodrag

    2014-05-01

    We report on the identification and functional characterization of HMGB1 of the goldfish. Quantitative analysis indicated the highest expression of goldfish HMGB1 in the brain, with lower mRNA levels in spleen, intestine, kidney, gill and heart. HMGB1 was also differentially expressed in goldfish immune cell populations with highest mRNA levels present in splenocytes and neutrophils. We generated and functionally characterized the recombinant HMGB1 (rgHMGB1). The rgHMGB1 primed the respiratory burst response in monocytes and induced nitric oxide production of primary goldfish macrophages. Treatment of goldfish macrophages with heat-killed Mycobacterium marinum and Aeromonas salmonicida elevated the expression of HMGB1 and resulted in higher HMGB1 protein levels. The rgHMGB1 induced a dose-dependent production of TNFα-2 and IL-1β1 of goldfish macrophages. Furthermore, the dual luciferase reporter assay revealed that goldfish HMGB1 induced the activation of the NF-κB signaling pathway. Our results indicate that goldfish HMGB1 is a critical regulatory cytokine of inflammatory and antimicrobial response of the goldfish. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Y-box-binding protein-1 (YB-1) promotes cell proliferation, adhesion and drug resistance in diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Xiaobing; Wu, Yaxun [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); Wang, Yuchan [Department of Pathogen, Medical College, Nantong University, Nantong 226001, Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu (China); Zhu, Xinghua; Yin, Haibing [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); He, Yunhua [Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu (China); Li, Chunsun; Liu, Yushan; Lu, Xiaoyun; Chen, Yali; Shen, Rong [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); Xu, Xiaohong, E-mail: xuxiaohongnantong@126.com [Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); He, Song, E-mail: hesongnt@126.com [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China)

    2016-08-15

    YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1{sup S102} were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1{sup S102} nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion-mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner. - Highlights: • The expression statuses of YB-1 and pYB-1{sup S102} are reversely correlated with outcomes of DLBCL patients. • YB-1 promotes cell proliferation by accelerating G1/S transition in DLBCL. • YB-1 confers drug resistance to mitoxantrone in DLBCL.

  20. 46 CFR 111.81-1 - Outlet boxes and junction boxes; general.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Outlet boxes and junction boxes; general. 111.81-1... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Outlet Boxes and Junction Boxes § 111.81-1 Outlet boxes and junction boxes; general. (a) The requirements of this subpart apply to each outlet box used with a lighting...

  1. Investigation of reference gene expression during human herpesvirus 6B infection indicates peptidylprolyl isomerase A as a stable reference gene and TATA box binding protein as a gene up-regulated by this virus.

    Science.gov (United States)

    Engdahl, Elin; Dunn, Nicky; Fogdell-Hahn, Anna

    2016-01-01

    When using relative gene expression for quantification of RNA it is crucial that the reference genes used for normalization do not change with the experimental condition. We aimed at investigating the expressional stability of commonly used reference genes during Human herpesvirus 6B (HHV-6B) infection. Expression of eight commonly used reference genes were investigated with quantitative PCR in a T-cell line infected with HHV-6B. The stability of genes was investigated using the 2(-ΔΔCT) method and the algorithms BestKeeper, GeNorm and NormFinder. Our results indicate that peptidylprolyl isomerase A (PPIA) is the most stably expressed gene while TATA box binding protein (TBP) is the least stably expressed gene during HHV-6B infection. In a confirmatory experiment, TBP was demonstrated to be dose and time dependently upregulated by HHV-6B. The stability of PPIA is in line with other studies investigating different herpesvirus infections whereas the finding that HHV-6B significantly upregulates TBP is novel and most likely specific to HHV-6B. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. The interaction of hyperthermophilic TATA-box binding protein with single-stranded DNA is entropically favorable and exhibits a large negative heat capacity change at high salt concentration.

    Science.gov (United States)

    Nagatoishi, Satoru; Tanaka, Yoshikazu; Kudou, Motonori; Tsumoto, Kouhei

    2009-09-01

    We have investigated the thermodynamics of the interaction between the TATA-box-binding protein from Pyrococcus horikoshii (PhoTBP) and its target DNA (TATA-1). The interaction between PhoTBP and double-stranded DNA (dsDNA) is entropically favorable and enthalpically unfavorable. The thermodynamic parameters for TATA-1 duplex formation in the presence of PhoTBP, that is, ternary PhoTBP-dsDNA complexation, are similar to those for TATA-1 duplex formation, which is enthalpically favorable. Surface plasmon resonance analysis indicates that the interaction between PhoTBP and single-stranded DNA (ssDNA) of TATA-1 is entropy driven and has a large negative heat capacity change (-1.19 kcal mol(-1) K(-1)) at high salt concentration (800 mM NaCl). These results suggest that the favorable entropic effect corresponding to the interaction between PhoTBP and dsDNA is due not to ternary complexation but to the interaction between PhoTBP and ssDNA. This report is the first to describe the thermodynamics of the interaction between TBP and ssDNA.

  3. Coincidence-counting corrections for accidental coincidences, set dead time and intrinsic dead time

    International Nuclear Information System (INIS)

    Wyllie, H.A.

    1998-01-01

    An equation is derived for calculating the radioactivity of a source from the results of coincidence counting, taking into account dead-time losses and accidental coincidences. The corrections allow for the extension of the set dead time in the p channel by the intrinsic dead time. Experimental verification shows improvement over a previous equation. (author)

  4. The Classroom Animal: Box Turtles.

    Science.gov (United States)

    Kramer, David C.

    1986-01-01

    Provides basic information on the anatomy, physiology, behaviors, and distribution patterns of the box turtle. Offers suggestions for the turtle's care and maintenance in a classroom environment. (ML)

  5. Acsys in a box

    International Nuclear Information System (INIS)

    Briegel, C.; Finstrom, D.; Hendricks, B.; King, C.; Lackey, S.; Neswold, R.; Nicklaus, D.; Patrick, J.; Petrov, A.; Rechenmacher, R.; Schumann, C.; Smedinghoff, J.

    2012-01-01

    The Accelerator Control System (ACSYS) at Fermilab has evolved to enable this relatively large control system to be encapsulated into a 'box' such as a laptop. The goal was to provide a platform isolated from the 'online' control system. This platform can be used internally for making major upgrades and modifications without impacting operations. It also provides a stand-alone environment for research and development including a turnkey control system for collaborators. Over time, the code base running on Scientific Linux has enabled all the salient features of the Fermilab's control system to be captured in an off-the-shelf laptop. The anticipated additional benefits of packaging the system include improved maintenance, reliability, documentation, and future enhancements. (authors)

  6. ACYSYS in a box

    Energy Technology Data Exchange (ETDEWEB)

    Briegel, C.; Finstrom, D.; Hendricks, B.; King, C.; Lackey, S.; Neswold, R.; Nicklaus, D.; Patrick, J.; Petrov, A.; Rechenmacher, R.; Schumann, C.; /Fermilab

    2011-11-01

    The Accelerator Control System at Fermilab has evolved to enable this relatively large control system to be encapsulated into a 'box' such as a laptop. The goal was to provide a platform isolated from the 'online' control system. This platform can be used internally for making major upgrades and modifications without impacting operations. It also provides a standalone environment for research and development including a turnkey control system for collaborators. Over time, the code base running on Scientific Linux has enabled all the salient features of the Fermilab's control system to be captured in an off-the-shelf laptop. The anticipated additional benefits of packaging the system include improved maintenance, reliability, documentation, and future enhancements.

  7. Raising the Dead without a Red Sea-Dead Sea project? Hydro-economics and governance

    Directory of Open Access Journals (Sweden)

    D. E. Rosenberg

    2011-04-01

    Full Text Available Seven decades of extractions have dramatically reduced Jordan River flows, lowered the Dead Sea level, opened sink holes, and caused other environmental problems. The fix Jordan, Israel, and the Palestinians propose would build an expensive multipurpose conveyance project from the Red Sea to the Dead Sea that would also generate hydropower and desalinate water. This paper compares the Red-Dead project to alternatives that may also raise the Dead Sea level. Hydro-economic model results for the Jordan-Israel-Palestinian inter-tied water systems show two restoration alternatives are more economically viable than the proposed Red-Dead project. Many decentralized new supply, wastewater reuse, conveyance, conservation, and leak reduction projects and programs in each country can together increase economic benefits and reliably deliver up to 900 MCM yr−1 to the Dead Sea. Similarly, a smaller Red-Dead project that only generates hydropower can deliver large flows to the Dead Sea when the sale price of generated electricity is sufficiently high. However, for all restoration options, net benefits fall and water scarcity rises as flows to the Dead Sea increase. This finding suggests (i each country has no individual incentive to return water to the Dead Sea, and (ii outside institutions that seek to raise the Dead must also offer countries direct incentives to deliver water to the Sea besides building the countries new infrastructure.

  8. What Makes a Better Box?

    Science.gov (United States)

    Moyer, Richard; Everett, Susan

    2010-01-01

    Every morning, many Americans start their day with a bowl of cereal. Some spend time while they eat breakfast reading the back of the cereal box, but few consider its size, shape, and construction, or realize that it was designed by an engineer. This article describes a lesson in which students design, build, and critique cereal boxes. The lesson…

  9. Spirit Boxes: Expressions of Culture.

    Science.gov (United States)

    DeMuro, Ted

    1984-01-01

    After studying the culture and art of the ancient civilizations of South America, Mesopotamia, Greece, and Egypt, secondary level art students made spirit boxes as expressions of the various cultures. How to make the boxes and how to prepare the face molds are described. (RM)

  10. The RNA Helicase DeaD Stimulates ExsA Translation To Promote Expression of the Pseudomonas aeruginosa Type III Secretion System

    Science.gov (United States)

    Intile, Peter J.; Balzer, Grant J.; Wolfgang, Matthew C.

    2015-01-01

    ABSTRACT The Pseudomonas aeruginosa type III secretion system (T3SS) is a primary virulence factor important for phagocytic avoidance, disruption of host cell signaling, and host cell cytotoxicity. ExsA is the master regulator of T3SS transcription. The expression, synthesis, and activity of ExsA is tightly regulated by both intrinsic and extrinsic factors. Intrinsic regulation consists of the well-characterized ExsECDA partner-switching cascade, while extrinsic factors include global regulators that alter exsA transcription and/or translation. To identify novel extrinsic regulators of ExsA, we conducted a transposon mutagenesis screen in the absence of intrinsic control. Transposon disruptions within gene PA2840, which encodes a homolog of the Escherichia coli RNA-helicase DeaD, significantly reduced T3SS gene expression. Recent studies indicate that E. coli DeaD can promote translation by relieving inhibitory secondary structures within target mRNAs. We report here that PA2840, renamed DeaD, stimulates ExsA synthesis at the posttranscriptional level. Genetic experiments demonstrate that the activity of an exsA translational fusion is reduced in a deaD mutant. In addition, exsA expression in trans fails to restore T3SS gene expression in a deaD mutant. We hypothesized that DeaD relaxes mRNA secondary structure to promote exsA translation and found that altering the mRNA sequence of exsA or the native exsA Shine-Dalgarno sequence relieved the requirement for DeaD in vivo. Finally, we show that purified DeaD promotes ExsA synthesis using in vitro translation assays. Together, these data reveal a novel regulatory mechanism for P. aeruginosa DeaD and add to the complexity of global regulation of T3SS. IMPORTANCE Although members of the DEAD box family of RNA helicases are appreciated for their roles in mRNA degradation and ribosome biogenesis, an additional role in gene regulation is now emerging in bacteria. By relaxing secondary structures in mRNAs, DEAD box

  11. Antigen-specific over-expression of human cartilage glycoprotein 39 on CD4+ CD25+ forkhead box protein 3+ regulatory T cells in the generation of glucose-6-phosphate isomerase-induced arthritis.

    Science.gov (United States)

    Tanaka, Y; Matsumoto, I; Inoue, A; Umeda, N; Takai, C; Sumida, T

    2014-08-01

    Human cartilage gp-39 (HC gp-39) is a well-known autoantigen in rheumatoid arthritis (RA). However, the exact localization, fluctuation and function of HC gp-39 in RA are unknown. Therefore, using a glucose-6-phosphate isomerase (GPI)-induced model of arthritis, we investigated these aspects of HC gp-39 in arthritis. The rise in serum HC gp-39 levels was detected on the early phase of GPI-induced arthritis (day 7) and the HC gp-39 mRNA was increased significantly on splenic CD4(+) T cells on day7, but not on CD11b(+) cells. Moreover, to identify the characterization of HC gp-39(+) CD4(+) T cells, we assessed the analysis of T helper (Th) subsets. As a result, HC gp-39 was expressed dominantly in CD4(+) CD25(+) forkhead box protein 3 (FoxP3)(+) refulatory T cells (T(reg)), but not in Th1, Th2 or Th17 cells. Furthermore, to investigate the effect of HC gp-39 to CD4(+) T cells, T cell proliferation assay and cytokine production from CD4(+) T cells using recombinant HC gp-39 was assessed. We found that GPI-specific T cell proliferation and interferon (IFN)-γ or interleukin (IL)-17 production were clearly suppressed by addition of recombinant HC gp-39. Antigen-specific over-expression of HC gp-39 in splenic CD4(+) CD25(+) FoxP3(+) T(reg) cells occurs in the induction phase of GPI-induced arthritis, and addition of recombinant HC gp-39 suppresses antigen-specific T-cell proliferation and cytokine production, suggesting that HC gp-39 in CD4(+) T cells might play a regulatory role in arthritis. © 2014 British Society for Immunology.

  12. Thinking Inside the Box

    International Nuclear Information System (INIS)

    Boeheim, Charles T.

    2007-01-01

    In early 2007, SLAC was faced with a shortage of both electrical power and cooling in the main computer building, at the same time that the BaBar collaboration needed a new cluster of 250 batch machines installed. A number of different options were explored for the expansion. Provision of additional electrical power to the building was estimated to take one to two years, and cost several million dollars; additional cooling was even worse. Space in a Silicon Valley co-location facilities was reasonable on a one-year timescale, but broke even in costs by the end of three years, and were more expensive after that. There were also unresolved questions about the affects of additional latency from an offsite compute cluster to the onsite disk servers. The option of converting existing experimental hall space into computer space was estimated at one year, with uncertain availability. An option to aggressively replace several existing clusters with more power-efficient equipment was studied closely, but was disruptive to continued operations, expensive, and didn't provide any additional headroom. Finally, the installation of a Sun Project Blackbox (PBB) unit was selected as providing the capacity on a timescale of six months for a reasonable cost with minimal disruption to service. SLAC obtained and installed a beta unit and have been running it in production since September 2007. The experiences described are with the Early Access version of the PBB. The production version of the box has engineering changes based in part on our experiences

  13. Measurement of the Dead-Time in a Multichannel Analyser

    DEFF Research Database (Denmark)

    Mortensen, L.; Olsen, J.

    1973-01-01

    By means of two simple measurements three different dead-times are determined: the normal dead-time, a dead-time coming from the pile-up, and a dead-time due to the finite width of the timing pulses.......By means of two simple measurements three different dead-times are determined: the normal dead-time, a dead-time coming from the pile-up, and a dead-time due to the finite width of the timing pulses....

  14. Learning Intelligent Dialogs for Bounding Box Annotation

    OpenAIRE

    Konyushkova, Ksenia; Uijlings, Jasper; Lampert, Christoph; Ferrari, Vittorio

    2017-01-01

    We introduce Intelligent Annotation Dialogs for bounding box annotation. We train an agent to automatically choose a sequence of actions for a human annotator to produce a bounding box in a minimal amount of time. Specifically, we consider two actions: box verification [37], where the annotator verifies a box generated by an object detector, and manual box drawing. We explore two kinds of agents, one based on predicting the probability that a box will be positively verified, and the other bas...

  15. Identification of the DEAD box RNA helicase DDX3 as a therapeutic target in colorectal cancer.

    Science.gov (United States)

    Heerma van Voss, Marise R; Vesuna, Farhad; Trumpi, Kari; Brilliant, Justin; Berlinicke, Cynthia; de Leng, Wendy; Kranenburg, Onno; Offerhaus, G Johan; Bürger, Horst; van der Wall, Elsken; van Diest, Paul J; Raman, Venu

    2015-09-29

    Identifying druggable targets in the Wnt-signaling pathway can optimize colorectal cancer treatment. Recent studies have identified a member of the RNA helicase family DDX3 (DDX3X) as a multilevel activator of Wnt signaling in cells without activating mutations in the Wnt-signaling pathway. In this study, we evaluated whether DDX3 plays a role in the constitutively active Wnt pathway that drives colorectal cancer. We determined DDX3 expression levels in 303 colorectal cancers by immunohistochemistry. 39% of tumors overexpressed DDX3. High cytoplasmic DDX3 expression correlated with nuclear β-catenin expression, a marker of activated Wnt signaling. Functionally, we validated this finding in vitro and found that inhibition of DDX3 with siRNA resulted in reduced TCF4-reporter activity and lowered the mRNA expression levels of downstream TCF4-regulated genes. In addition, DDX3 knockdown in colorectal cancer cell lines reduced proliferation and caused a G1 arrest, supporting a potential oncogenic role of DDX3 in colorectal cancer. RK-33 is a small molecule inhibitor designed to bind to the ATP-binding site of DDX3. Treatment of colorectal cancer cell lines and patient-derived 3D cultures with RK-33 inhibited growth and promoted cell death with IC50 values ranging from 2.5 to 8 μM. The highest RK-33 sensitivity was observed in tumors with wild-type APC-status and a mutation in CTNNB1. Based on these results, we conclude that DDX3 has an oncogenic role in colorectal cancer. Inhibition of DDX3 with the small molecule inhibitor RK-33 causes inhibition of Wnt signaling and may therefore be a promising future treatment strategy for a subset of colorectal cancers.

  16. DEAD-box RNA helicase is dispensable for mitochondrial translation in Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

    Richterová, Lenka; Vávrová, Zuzana; Lukeš, Julius

    2011-01-01

    Roč. 127, č. 1 (2011), 300-303 ISSN 0014-4894 R&D Projects: GA ČR GA204/09/1667; GA MŠk LC07032; GA MŠk 2B06129 Institutional research plan: CEZ:AV0Z60220518 Keywords : Trypanosoma * Mitochondrial translation * RNA helicase * Cytochrome c oxidase * Mitochondrion Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.122, year: 2011

  17. Microclimate boxes for panel paintings

    DEFF Research Database (Denmark)

    Wadum, Jørgen

    1998-01-01

    The use of microclimate boxes to protect vulnerable panel paintings is, therefore, not a new phenomenon of the past two or three decades. Rather, it has been a concern for conservators and curators to protect these objects of art at home and in transit since the end of the nineteenth century....... The increased number of travelling exhibitions in recent years has heightened the need to protect paintings during circulation (Thomson 1961; Mecklenburg 1991). The use and design of microclimate boxes have been evolving since 1892. These boxes may be divided into three broad groups: those using an active...

  18. A new set of ESTs from chickpea (Cicer arietinum L. embryo reveals two novel F-box genes, CarF-box_PP2 and CarF-box_LysM, with potential roles in seed development.

    Directory of Open Access Journals (Sweden)

    Shefali Gupta

    Full Text Available Considering the economic importance of chickpea (C. arietinum L. seeds, it is important to understand the mechanisms underlying seed development for which a cDNA library was constructed from 6 day old chickpea embryos. A total of 8,186 ESTs were obtained from which 4,048 high quality ESTs were assembled into 1,480 unigenes that majorly encoded genes involved in various metabolic and regulatory pathways. Of these, 95 ESTs were found to be involved in ubiquitination related protein degradation pathways and 12 ESTs coded specifically for putative F-box proteins. Differential transcript accumulation of these putative F-box genes was observed in chickpea tissues as evidenced by quantitative real-time PCR. Further, to explore the role of F-box proteins in chickpea seed development, two F-box genes were selected for molecular characterization. These were named as CarF-box_PP2 and CarF-box_LysM depending on their C-terminal domains, PP2 and LysM, respectively. Their highly conserved structures led us to predict their target substrates. Subcellular localization experiment revealed that CarF-box_PP2 was localized in the cytoplasm and CarF-box_LysM was localized in the nucleus. We demonstrated their physical interactions with SKP1 protein, which validated that they function as F-box proteins in the formation of SCF complexes. Sequence analysis of their promoter regions revealed certain seed specific cis-acting elements that may be regulating their preferential transcript accumulation in the seed. Overall, the study helped in expanding the EST database of chickpea, which was further used to identify two novel F-box genes having a potential role in seed development.

  19. A new set of ESTs from chickpea (Cicer arietinum L.) embryo reveals two novel F-box genes, CarF-box_PP2 and CarF-box_LysM, with potential roles in seed development.

    Science.gov (United States)

    Gupta, Shefali; Garg, Vanika; Bhatia, Sabhyata

    2015-01-01

    Considering the economic importance of chickpea (C. arietinum L.) seeds, it is important to understand the mechanisms underlying seed development for which a cDNA library was constructed from 6 day old chickpea embryos. A total of 8,186 ESTs were obtained from which 4,048 high quality ESTs were assembled into 1,480 unigenes that majorly encoded genes involved in various metabolic and regulatory pathways. Of these, 95 ESTs were found to be involved in ubiquitination related protein degradation pathways and 12 ESTs coded specifically for putative F-box proteins. Differential transcript accumulation of these putative F-box genes was observed in chickpea tissues as evidenced by quantitative real-time PCR. Further, to explore the role of F-box proteins in chickpea seed development, two F-box genes were selected for molecular characterization. These were named as CarF-box_PP2 and CarF-box_LysM depending on their C-terminal domains, PP2 and LysM, respectively. Their highly conserved structures led us to predict their target substrates. Subcellular localization experiment revealed that CarF-box_PP2 was localized in the cytoplasm and CarF-box_LysM was localized in the nucleus. We demonstrated their physical interactions with SKP1 protein, which validated that they function as F-box proteins in the formation of SCF complexes. Sequence analysis of their promoter regions revealed certain seed specific cis-acting elements that may be regulating their preferential transcript accumulation in the seed. Overall, the study helped in expanding the EST database of chickpea, which was further used to identify two novel F-box genes having a potential role in seed development.

  20. Dead pixel replacement in LWIR microgrid polarimeters.

    Science.gov (United States)

    Ratliff, Bradley M; Tyo, J Scott; Boger, James K; Black, Wiley T; Bowers, David L; Fetrow, Matthew P

    2007-06-11

    LWIR imaging arrays are often affected by nonresponsive pixels, or "dead pixels." These dead pixels can severely degrade the quality of imagery and often have to be replaced before subsequent image processing and display of the imagery data. For LWIR arrays that are integrated with arrays of micropolarizers, the problem of dead pixels is amplified. Conventional dead pixel replacement (DPR) strategies cannot be employed since neighboring pixels are of different polarizations. In this paper we present two DPR schemes. The first is a modified nearest-neighbor replacement method. The second is a method based on redundancy in the polarization measurements.We find that the redundancy-based DPR scheme provides an order-of-magnitude better performance for typical LWIR polarimetric data.

  1. Surviving Sepsis: Taming a Deadly Immune Response

    Science.gov (United States)

    ... Issues Subscribe August 2014 Print this issue Surviving Sepsis Taming a Deadly Immune Response En español Send ... Mouth? Looking at Lupus Wise Choices Signs of Sepsis Sepsis can be hard to spot, because its ...

  2. The dead seed coat functions as a long-term storage for active hydrolytic enzymes

    Science.gov (United States)

    Raviv, Buzi; Aghajanyan, Lusine; Granot, Gila; Makover, Vardit; Frenkel, Omer; Gutterman, Yitzchak

    2017-01-01

    Seed development culminates in programmed cell death (PCD) and hardening of organs enclosing the embryo (e.g., pericarp, seed coat) providing essentially a physical shield for protection during storage in the soil. We examined the proposal that dead organs enclosing embryos are unique entities that store and release upon hydration active proteins that might increase seed persistence in soil, germination and seedling establishment. Proteome analyses of dead seed coats of Brassicaceae species revealed hundreds of proteins being stored in the seed coat and released upon hydration, many are stress-associated proteins such as nucleases, proteases and chitinases. Functional analysis revealed that dead seed coats function as long-term storage for multiple active hydrolytic enzymes (e.g., nucleases) that can persist in active forms for decades. Substances released from the dead seed coat of the annual desert plant Anastatica hierochuntica displayed strong antimicrobial activity. Our data highlighted a previously unrecognized feature of dead organs enclosing embryos (e.g., seed coat) functioning not only as a physical shield for embryo protection but also as a long-term storage for active proteins and other substances that are released upon hydration to the “seedsphere” and could contribute to seed persistence in the soil, germination and seedling establishment. PMID:28700755

  3. Dead Trees Bring Life to Forest Critters

    Science.gov (United States)

    Thomas Nicholls; Mike Ostry

    2003-01-01

    What good is a dying or dead tree in a forest? Dead and dying trees don't awe us with their beauty; they just stand or lie there on the forest floor, offering no promise of lumber or other wood products we need. But if we look more closely at such trees, we may see lots of life in them: a raccoon family huddled in a burrow, a downy woodpecker excavating another...

  4. Dead reckoning and distributed interactive simulation

    Science.gov (United States)

    Lin, Kuo-Chi

    1995-04-01

    This paper analyzes the use of dead reckoning in Distributed Interactive Simulation. The purpose of dead reckoning is to reduce the updates required by each simulator on the network to better utilize the available bandwidth. Extrapolation formulas are derived and discussed based on network communication traffic and the amount of computation performed by simulators. Smoothing and delay compensation algorithms are also discussed. Numerical and human perspective experiment are conducted. A software tool that assesses the performance of the read reckoning algorithm is introduced.

  5. DIRECT KICKS IN BOXING

    Directory of Open Access Journals (Sweden)

    Izet Kahrović

    2009-11-01

    Full Text Available Hit directly, giving any impact maximum muscle strength is skill, and it is neces- sary to the exercise and learning to make it perfect. Training begins with oral statement, so that students get to know with the techni- que that works. After oral exposure, it is necessary to create a good notion on technology that is adopted. The best way for the creation of good notion is a good demonstration. In direct training kicks in the box, you need patience and gradualness and there- fore uses a large number of additional exercises. In their work with beginners, in the first class, individual elements of technology, and also direct blow, it is necessary to separate the parts and run them on multiple commands, to later come to the confluence in one command. Direct wounds, with left and right hand, can be run from the towns, on the head and body, from the movement, to step forward, step back and step aside, the remedy to the left and right side. Left direct is taking out from a running protrusion hands, but kick, which is a pro- duct of the system, ankle-knee-pelvis and shoulder forward horizontaly. Set at the time of stripes, body weight over the left leg. Right direct from the place, starting ekscentrical reflecsive impuls of a extensor muscle in ankle, knee and joint of a hip.This kind of a sud- den movement is running simultaneously with the rotation of the body around vertical (longitudinal axis, with the transfer body weight on the left leg. Further movement to the hand which serves as a lever, which is transmitted through the power stroke

  6. First experimental evidence that a harvestman (Arachnida: Opiliones detects odors of non-rotten dead prey by olfaction

    Directory of Open Access Journals (Sweden)

    Thaiany Miranda Costa

    2013-06-01

    Full Text Available Harvestmen feed on live, dead and fresh, or decomposing animals, fungi, and plant matter, being very dependent on chemoreception to find food. Herein we performed an experiment to test if individuals of Discocyrtus pectinifemur Mello-Leitão, 1937 (Gonyleptidae (n = 23 behave differently when in contact with olfactory cues from different sources (rotten prey, non-rotten prey and a control. Using dead crickets in a box covered with a mesh, and recording the time the harvestmen spent in the vicinities of the box, we show that D. pectinifemur detects non-rotten prey and stays longer on it than on the other two treatments. Our results contrast with a previous study on another species, showing that we should not generalize results obtained for one species. Our data also suggest that olfactory receptors occur on the legs of these harvestmen and that D. pectinifemur might choose dietary items based on olfaction.

  7. Article-in-a-Box

    Indian Academy of Sciences (India)

    Volume 1 Issue 5 May 1996 pp 2-2 Article-in-a-Box. Chief Editor's column / The First Electronic Computer · V Rajaraman · More Details Fulltext PDF. Volume 1 Issue 6 June 1996 pp 2-4 Article-in-a-Box. Konrad Lorenz · Raghavendra Gadagkar · More Details Fulltext PDF. Volume 1 Issue 8 August 1996 pp 3-4 Article-in-a- ...

  8. Fuel element box inspection device

    International Nuclear Information System (INIS)

    Ortmayer, R.M.; Pick, W.

    1985-01-01

    The invention concerns a device for inspecting the outer geometry of a long fuel element box by measuring the surface contours over its longitudinal crossection and along its length by sensors. These are kept in a sledge which can be moved along the fuel element guide in a slot guide. The measurement signals reach an evaluation device outside the longitudinal box. (orig./HP) [de

  9. RNAa Induced by TATA Box-Targeting MicroRNAs.

    Science.gov (United States)

    Zhang, Yijun; Zhang, Hui

    2017-01-01

    Recent studies reveal that some nuclear microRNAs (miRNA) and synthesized siRNAs target gene promoters to activate gene transcription (RNAa). Interestingly, our group identified a novel HIV-1-encoded miRNA, miR-H3, which targets specifically the core promoter TATA box of HIV-1 and activates viral gene expression. Depletion of miR-H3 significantly impaired the replication of HIV-1. miR-H3 mimics could activate viruses from CD4 + T cells isolated from patients receiving suppressive highly active antiretroviral therapy, which is very intriguing for reducing HIV-1 latent reservoir. Further study revealed that many cellular miRNAs also function like miR-H3. For instance, let-7i targets the TATA box of the interleukin-2 (IL-2) promoter and upregulates IL-2 expression in T-lymphocytes. In RNAa induced by TATA box-targeting miRNAs, Argonaute (AGO) proteins are needed, but there is no evidence for the involvement of promoter-associated transcripts or epigenetic modifications. We propose that the binding of small RNA-AGO complex to TATA box could facilitate the assembly of RNA Polymerase II transcription preinitiation complex. In addition, synthesized small RNAs targeting TATA box can also efficiently activate transcription of interested genes, such as insulin, IL-2, and c-Myc. The discovery of RNAa induced by TATA box-targeting miRNA provides an easy-to-use tool for activating gene expression.

  10. Two high-mobility group box domains act together to underwind and kink DNA

    International Nuclear Information System (INIS)

    Sánchez-Giraldo, R.; Acosta-Reyes, F. J.; Malarkey, C. S.; Saperas, N.; Churchill, M. E. A.; Campos, J. L.

    2015-01-01

    The crystal structure of HMGB1 box A bound to an unmodified AT-rich DNA fragment is reported at a resolution of 2 Å. A new mode of DNA recognition for HMG box proteins is found in which two box A domains bind in an unusual configuration generating a highly kinked DNA structure. High-mobility group protein 1 (HMGB1) is an essential and ubiquitous DNA architectural factor that influences a myriad of cellular processes. HMGB1 contains two DNA-binding domains, box A and box B, which have little sequence specificity but have remarkable abilities to underwind and bend DNA. Although HMGB1 box A is thought to be responsible for the majority of HMGB1–DNA interactions with pre-bent or kinked DNA, little is known about how it recognizes unmodified DNA. Here, the crystal structure of HMGB1 box A bound to an AT-rich DNA fragment is reported at a resolution of 2 Å. Two box A domains of HMGB1 collaborate in an unusual configuration in which the Phe37 residues of both domains stack together and intercalate the same CG base pair, generating highly kinked DNA. This represents a novel mode of DNA recognition for HMGB proteins and reveals a mechanism by which structure-specific HMG boxes kink linear DNA

  11. First-aid boxes - Reminder

    CERN Multimedia

    GS Department

    2010-01-01

    With a view to ensuring optimum use of the first-aid boxes on the CERN site, we should like to remind you of various changes introduced in March 2009: The TSO of the buildings concerned is responsible for the first-aid boxes, including checking their contents.   First-aid boxes may be restocked ONLY at the CERN stores (SCEM No. 54.99.80). This is no longer possible at the Infirmary. The associated cost is charged to the Departments.   First-aid boxes should be used only for mild injuries. All other cases should be referred to the Medical Service Infirmary (Bldg. 57 – ground-floor, tel. 73802) between 8.00 a.m. and 5.30 p.m. or to the Fire and Rescue Service (tel. 74444). N.B.: This information does not apply to the red emergency first-aid boxes in the underground areas or to the emergency kits for use in the event of being splashed with hydrofluoric acid.

  12. Box graphs and resolutions I

    Directory of Open Access Journals (Sweden)

    Andreas P. Braun

    2016-04-01

    Full Text Available Box graphs succinctly and comprehensively characterize singular fibers of elliptic fibrations in codimension two and three, as well as flop transitions connecting these, in terms of representation theoretic data. We develop a framework that provides a systematic map between a box graph and a crepant algebraic resolution of the singular elliptic fibration, thus allowing an explicit construction of the fibers from a singular Weierstrass or Tate model. The key tool is what we call a fiber face diagram, which shows the relevant information of a (partial toric triangulation and allows the inclusion of more general algebraic blowups. We shown that each such diagram defines a sequence of weighted algebraic blowups, thus providing a realization of the fiber defined by the box graph in terms of an explicit resolution. We show this correspondence explicitly for the case of SU(5 by providing a map between box graphs and fiber faces, and thereby a sequence of algebraic resolutions of the Tate model, which realizes each of the box graphs.

  13. Decontamination of TRU glove boxes

    International Nuclear Information System (INIS)

    Crawford, J.H.

    1978-03-01

    Two glove boxes that had been used for work with transuranic nuclides (TRU) for about 12 years were decontaminated in a test program to collect data for developing a decontamination facility for large equipment highly contaminated with alpha emitters. A simple chemical technique consisting of a cycle of water flushes and alkaline permanganate and oxalic acid washes was used for both boxes. The test showed that glove boxes and similar equipment that are grossly contaminated with transuranic nuclides can be decontaminated to the current DIE nonretrievable disposal guide of <10 nCi TRU/g with a moderate amount of decontamination solution and manpower. Decontamination of the first box from an estimated 1.3 Ci to about 5 mCi (6 nCi/g) required 1.3 gallons of decontamination solution and 0.03 man-hour of work for each square foot of surface area. The second box was decontaminated from an estimated 3.4 Ci to about 2.8 mCi (4.2 nCi/g) using 0.9 gallon of decontamination solution and 0.02 man-hour for each square foot of surface area. Further reductions in contamination were achieved by repetitive decontamination cycles, but the effectiveness of the technique decreased sharply after the initial cycle

  14. Functional characterization of MADS box transcription factors in Petunia hybrida

    NARCIS (Netherlands)

    Ferrario, S.I.T.

    2004-01-01

    Transcription factors play a central role in the regulation and integration of several developmental pathways in all organisms. MADS box proteins are, among transcription factors, key players in the regulation of flower induction, flower architecture and vegetative development and have been isolated

  15. Virtually Dead: Digital Public Mortuary Archaeology

    Directory of Open Access Journals (Sweden)

    Howard Williams

    2015-12-01

    Full Text Available Over recent decades, the ethics, politics and public engagements of mortuary archaeology have received sustained scrutiny, including how we handle, write about and display the archaeological dead. Yet the burgeoning use of digital media to engage different audiences in the archaeology of death and burial have so far escaped attention. This article explores categories and strategies by which digital media create virtual communities engaging with mortuary archaeology. Considering digital public mortuary archaeology (DPMA as a distinctive theme linking archaeology, mortality and material culture, we discuss blogs, vlogs and Twitter as case studies to illustrate the variety of strategies by which digital media can promote, educate and engage public audiences with archaeological projects and research relating to death and the dead in the human past. The article then explores a selection of key critical concerns regarding how the digital dead are currently portrayed, identifying the need for further investigation and critical reflection on DPMA’s aims, objectives and aspired outcomes.

  16. Dead Zone Accretion Flows in Protostellar Disks

    Science.gov (United States)

    Turner, Neal; Sano, T.

    2008-01-01

    Planets form inside protostellar disks in a dead zone where the electrical resistivity of the gas is too high for magnetic forces to drive turbulence. We show that much of the dead zone nevertheless is active and flows toward the star while smooth, large-scale magnetic fields transfer the orbital angular momentum radially outward. Stellar X-ray and radionuclide ionization sustain a weak coupling of the dead zone gas to the magnetic fields, despite the rapid recombination of free charges on dust grains. Net radial magnetic fields are generated in the magnetorotational turbulence in the electrically conducting top and bottom surface layers of the disk, and reach the midplane by ohmic diffusion. A toroidal component to the fields is produced near the midplane by the orbital shear. The process is similar to the magnetization of the solar tachocline. The result is a laminar, magnetically driven accretion flow in the region where the planets form.

  17. Dead sea transform fault system reviews

    CERN Document Server

    Garfunkel, Zvi; Kagan, Elisa

    2014-01-01

    The Dead Sea transform is an active plate boundary connecting the Red Sea seafloor spreading system to the Arabian-Eurasian continental collision zone. Its geology and geophysics provide a natural laboratory for investigation of the surficial, crustal and mantle processes occurring along transtensional and transpressional transform fault domains on a lithospheric scale and related to continental breakup. There have been many detailed and disciplinary studies of the Dead Sea transform fault zone during the last?20 years and this book brings them together.This book is an updated comprehensive coverage of the knowledge, based on recent studies of the tectonics, structure, geophysics, volcanism, active tectonics, sedimentology and paleo and modern climate of the Dead Sea transform fault zone. It puts together all this new information and knowledge in a coherent fashion.

  18. Identifying competencies of boxing coaches

    Directory of Open Access Journals (Sweden)

    Ioannis Tasiopoulos

    2014-10-01

    Full Text Available The purpose of this study was to find out the management skills required by boxing coaches to administrate their clubs. For the purposes of this study a scale was constructed which was answered by 98 boxing coaches. Explanatory factor analysis revealed seven factors: Communication-public relations (5 items, event management (4 items, management techniques (4 items, new technologies (4 items, prevention-safety (2 items, sport (5 items and sports facilities (2 items. The Cronbach of the scale was 0.85. The five competencies that rated by the coaches were: Supervisors of the area of training, maintaining excellent communication with athletes, using new technologies (e-mail, internet, handling disciplinary matters, accidents, complaints and reports on some sporting games and promoted harmony among athletes. We concluded that boxing coaches understand that the competencies required for meeting their obligations, were related to sports, prevention, safety and communications-public relations.

  19. Tunnel Diode Discriminator with Fixed Dead Time

    DEFF Research Database (Denmark)

    Diamond, J. M.

    1965-01-01

    A solid state discriminator for the range 0.4 to 10 V is described. Tunnel diodes are used for the discriminator element and in a special fixed dead time circuit. An analysis of temperature stability is presented. The regulated power supplies are described, including a special negative resistance...

  20. Swimming obstructed by dead-water

    NARCIS (Netherlands)

    Ganzevles, S.P.M; Nuland, F.S.W.; Maas, L.; Toussaint, H.M.

    2009-01-01

    In nautical literature, ‘dead-water’ refers to the obstructive effect encountered by ships moving in stratified water due to the ship generating waves on an interface that separates different water masses. To investigate the hypothesis that open water swimming may also be obstructed by an encounter

  1. Swimming obstructed by dead-water

    NARCIS (Netherlands)

    Ganzevles, S.P.; Nuland, F.S.; Maas, L.R.; Toussaint, H.M.

    2009-01-01

    In nautical literature, 'dead-water' refers to the obstructive effect encountered by ships moving in stratified water due to the ship generating waves on an interface that separates different water masses. To investigate the hypothesis that open water swimming may also be obstructed by an encounter

  2. Cheatgrass Dead Zones in Northern Nevada

    Science.gov (United States)

    Reports of areas of cheatgrass die-off are becoming more frequent. In 2009, we investigated cheatgrass die-off in north-central Nevada. Dead zones ranged from several to hundreds of acres in size and were largely unvegetated and covered by cheatgrass litter with a distinct gray cast. We collected re...

  3. Dinosaurs of India: Dead but Alive

    Indian Academy of Sciences (India)

    Table of contents. Dinosaurs of India: Dead but Alive · Fossils · Evolution and O2 PAL · The Science in Dinosaurs · Origin/ Extinction of Dinosaurs · PowerPoint Presentation · India –94my + 50my · Icehouse /Greenhouse through time · Global Mean Annual Temperature Distributions at 100 my · Global Mean Annual ...

  4. Glove boxes and similar containments

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    According to the present invention a glove box or similar containment is provided with an exhaust system including a vortex amplifier venting into the system, the vortex amplifier also having its main inlet in fluid flow connection with the containment and a control inlet in fluid flow connection with the atmosphere outside the containment. (U.S.)

  5. The Bird Box Survey Project

    Science.gov (United States)

    Willis, Patrick

    2014-01-01

    When high school students are asked what's the best part of science class, many will say it's the field trips. Students enjoy engaging in authentic, community-based science outside the classroom. To capitalize on this, Patrick Willis created the Bird Box Survey Project for his introductory field biology class. The project takes students…

  6. On the Dirichlet's Box Principle

    Science.gov (United States)

    Poon, Kin-Keung; Shiu, Wai-Chee

    2008-01-01

    In this note, we will focus on several applications on the Dirichlet's box principle in Discrete Mathematics lesson and number theory lesson. In addition, the main result is an innovative game on a triangular board developed by the authors. The game has been used in teaching and learning mathematics in Discrete Mathematics and some high schools in…

  7. Evaluation of bike boxes at signalized intersections.

    Science.gov (United States)

    Dill, Jennifer; Monsere, Christopher M; McNeil, Nathan

    2012-01-01

    This paper presents a before-after study of bike boxes at 10 signalized intersections in Portland, Oregon. The bike boxes, also known as advanced stop lines or advanced stop boxes, were installed to increase visibility of cyclists and reduce conflicts between motor vehicles and cyclists, particularly in potential "right-hook" situations. Before and after video were analyzed for seven intersections with green bike boxes, three intersections with uncolored bike boxes, and two control intersections. User perceptions were measured through surveys of cyclists passing through five of the bike box intersections and of motorists working downtown, where the boxes were concentrated. Both the observations and survey of motorists found a high rate of compliance and understanding of the markings. Overall, 73% of the stopping motor vehicles did not encroach at all into the bike box. Both motor vehicle and bicycle encroachment in the pedestrian crosswalk fell significantly at the bike box locations compared to the control intersections. The bike boxes had mixed effects on the motorists' encroachment in the bicycle lane. The number of observed conflicts at the bike box locations decreased, while the total number of cyclists and motor vehicles turning right increased. Negative-binomial models based upon the data predict fewer conflicts with the boxes, particularly as right-turning motor vehicle volumes increase. Observations of yielding behavior at two bike box and one control intersection found an improvement in motorists yielding to cyclists at the bike box locations. Differences in the traffic volumes and location contexts make firm conclusions about the effects of green coloring of the boxes difficult. Higher shares of surveyed motorists felt that the bike boxes made driving safer rather than more dangerous, even when the sample was narrowed to respondents who were not also cyclists. Over three-quarters of the surveyed cyclists thought that the boxes made the intersection safer

  8. Inosine Released from Dying or Dead Cells Stimulates Cell Proliferation via Adenosine Receptors.

    Science.gov (United States)

    Chen, Jin; Chaurio, Ricardo A; Maueröder, Christian; Derer, Anja; Rauh, Manfred; Kost, Andriy; Liu, Yi; Mo, Xianming; Hueber, Axel; Bilyy, Rostyslav; Herrmann, Martin; Zhao, Yi; Muñoz, Luis E

    2017-01-01

    Many antitumor therapies induce apoptotic cell death in order to cause tumor regression. Paradoxically, apoptotic cells are also known to promote wound healing, cell proliferation, and tumor cell repopulation in multicellular organisms. We aimed to characterize the nature of the regenerative signals concentrated in the micromilieu of dead and dying cells. Cultures of viable melanoma B16F10 cells, mouse fibroblasts, and primary human fibroblast-like synoviocytes (FLS) in the presence of dead and dying cells, their supernatants (SNs), or purified agonists and antagonists were used to evaluate the stimulation of proliferation. Viable cell quantification was performed by either flow cytometry of harvested cells or by crystal violet staining of adherent cells. High-performance liquid chromatography and liquid chromatography coupled with mass spectrometry of cell SNs were deployed to identify the nature of growth-promoting factors. Coimplantation of living cells in the presence of SNs collected from dead and dying cells and specific agonists was used to evaluate tumor growth in vivo . The stimulation of proliferation of few surviving cells by bystander dead cells was confirmed for melanoma cells, mouse fibroblasts, and primary FLS. We found that small soluble molecules present in the protein-free fraction of SNs of dead and dying cells were responsible for the promotion of proliferation. The nucleoside inosine released by dead and dying cells acting via adenosine receptors was identified as putative inducer of proliferation of surviving tumor cells after irradiation and heat treatment. Inosine released by dead and dying cells mediates tumor cell proliferation via purinergic receptors. Therapeutic strategies surmounting this pathway may help to reduce the rate of recurrence after radio- and chemotherapy.

  9. Gulf of Mexico dead zone - the last 150 years

    Science.gov (United States)

    Osterman, Lisa; Swarzenski, P.W.; Poore, R.Z.

    2006-01-01

    'Gulf of Mexico Dead Zone-The Last 150 Years' discusses the dead zone that forms seasonally in the northern Gulf of Mexico when subsurface waters become depleted in dissolved oxygen and cannot support most life.

  10. The Heuristic Interpretation of Box Plots

    Science.gov (United States)

    Lem, Stephanie; Onghena, Patrick; Verschaffel, Lieven; Van Dooren, Wim

    2013-01-01

    Box plots are frequently used, but are often misinterpreted by students. Especially the area of the box in box plots is often misinterpreted as representing number or proportion of observations, while it actually represents their density. In a first study, reaction time evidence was used to test whether heuristic reasoning underlies this…

  11. Standing dead tree resources in forests of the United States

    Science.gov (United States)

    Christopher W. Woodall; Karen L. Waddell; Christopher M. Oswalt; James E. Smith

    2013-01-01

    Given the importance of standing dead trees to numerous forest ecosystem attributes/ processes such as fuel loadings and wildlife habitat, the Forest Inventory and Analysis (FIA) Program of the Forest Service, U.S. Department of Agriculture, initiated a consistent nationwide inventory of standing dead trees in 1999. As the first cycle of annual standing dead tree...

  12. The zero inflation of standing dead tree carbon stocks

    Science.gov (United States)

    Christopher W. Woodall; David W. MacFarlane

    2012-01-01

    Given the importance of standing dead trees in numerous forest ecosystem attributes/processes such as carbon (C) stocks, the USDA Forest Service’s Forest Inventory and Analysis (FIA) program began consistent nationwide sampling of standing dead trees in 1999. Modeled estimates of standing dead tree C stocks are currently used as the official C stock estimates for the...

  13. Water box for steam generator

    International Nuclear Information System (INIS)

    Lecomte, Robert; Viaud, Michel.

    1975-01-01

    This invention relates to a water box for connecting an assembly composed of a vertical steam generator and a vertical pump to the vessel of the nuclear reactor, the assembly forming the primary cooling system of a pressurised water reactor. This invention makes it easy to dismantle the pump on the water box without significant loss of water in the primary cooling system of the reactor and particularly without it being necessary to drain the water contained in the steam generator beforehand. It makes it possible to shorten the time required for dismantling the primary pump in order to service or repair it and makes dismantling safer in that the dismantling does not involve draining the steam generator and therefore the critical storage of a large amount of cooling water that has been in contact with the fuel assemblies of the nuclear reactor core [fr

  14. Box-shaped halophilic bacteria.

    OpenAIRE

    Javor, B; Requadt, C; Stoeckenius, W

    1982-01-01

    Three morphologically similar strains of halophilic, box-shaped procaryotes have been isolated from brines collected in the Sinai, Baja California (Mexico), and southern California (United States). Although the isolates in their morphology resemble Walsby's square bacteria, which are a dominant morphological type in the Red Sea and Baja California brines, they are probably not identical to them. The cells show the general characteristics of extreme halophiles and archaebacteria. They contain ...

  15. Potential Evaporite Biomarkers from the Dead Sea

    Science.gov (United States)

    Morris, Penny A.; Wentworth, Susan J.; Thomas-Keprta, Kathie; Allen, Carlton C.; McKay, David S.

    2001-01-01

    The Dead Sea is located on the northern branch of the African-Levant Rift systems. The rift system, according to one model, was formed by a series of strike slip faults, initially forming approximately two million years ago. The Dead Sea is an evaporite basin that receives freshwater from springs and from the Jordan River. The Dead Sea is different from other evaporite basins, such as the Great Salt Lake, in that it possesses high concentrations of magnesium and has an average pH of 6.1. The dominant cation in the Great Salt Lake is sodium, and the pH is 7.7. Calcium concentrations are also higher in the Dead Sea than in the Great Salt Lake. Both basins are similar in that the dominant anion is chlorine and the salinity levels are approximately 20 %. Other common cations that have been identified from the waters of the Dead Sea and the Great Salt Lake include sodium and potassium. A variety of Archea, Bacteria, and a single genus of a green algal, Dunaliella, has been described from the Dead Sea. Earlier studies concentrated on microbial identification and analysis of their unique physiology that allows them to survive in this type of extreme environment. Potential microbial fossilization processes, microbial fossils, and the metallic ions associated with fossilization have not been studied thoroughly. The present study is restricted to identifying probable microbial morphologies and associated metallic ions. XRD (X Ray Diffraction) analysis indicates the presence of halite, quartz, and orthoclase feldspar. In addition to these minerals, other workers have reported potassium chloride, magnesium bromide, magnesium chloride, calcium chloride, and calcium sulfate. Halite, calcium sulfate, and orthoclase were examined in this report for the presence of microbes, microbially induced deposits or microbial alteration. Neither the gypsum nor the orthoclase surfaces possesses any obvious indications of microbial life or fossilization. The sand-sized orthoclase particles are

  16. Anisakis simplex: dangerous--dead and alive?

    Science.gov (United States)

    Audicana, María Teresa; Ansotegui, Ignacio J; de Corres, Luis Fernández; Kennedy, Malcolm W

    2002-01-01

    The risk of infection with Anisakis simplex and related parasites of fish has been recognized for some time, but it is now emerging that ingestion of material from dead parasites in food is also potentially dangerous. The resulting allergic reactions range from rapid onset and potentially lethal anaphylactic reactions to chronic, debilitating conditions. This review discusses the problems and clinical implications associated with A. simplex, other related conditions, and the way in which disease manifestations vary from person to person.

  17. Surviving deadness in the analytic experience.

    Science.gov (United States)

    Koritar, Endre

    2014-12-01

    The transference/countertransference (third space) analysis is considered to be central in the therapeutic effectiveness of the analytic process. Less emphasis has been placed on the actual experiences of analyst and analysand in the conflictual reenactment of third space experience and its resolution. This paper recounts the shared experience of a patient who was silent throughout most of the analysis, and my reaction, in fantasy and enactment, to this disturbing experience-both for him and for myself. I argue that it is the affective re-experiencing of past repressed trauma in the analytic space that has a therapeutic impact, leading to growth in the patient and also the therapist. I contrast Freud's emphasis on insight, making the unconscious conscious, with Ferenczi's suggestion that the therapeutic impact lies in the repetition of past traumatic experience in the analysis but with the possibility of a different outcome with a more benign object, leading to symbolic representation of repressed trauma. Re-experiencing and symbolization, in the third space, of past traumatic experience can be an exit point from the endless repetition of trauma in internal and external object relations, leading to a new beginning in the patient's life. Immersed in the experience of deadness in the analysis, which had become a dead womb, the struggle to remain alive and thinking led to a rupture out of the dead womb, like the Caesura of birth, into aliveness and the ability to mentalize what had previously remained unmentalized.

  18. Visualization of deuterium dead layer by atom probe tomography

    KAUST Repository

    Gemma, Ryota

    2012-12-01

    The first direct observation, by atom probe tomography, of a deuterium dead layer is reported for Fe/V multilayered film loaded with D solute atoms. The thickness of the dead layers was measured to be 0.4-0.5 nm. The dead layers could be distinguished from chemically intermixed layers. The results suggest that the dead layer effect occurs even near the interface of the mixing layers, supporting an interpretation that the dead layer effect cannot be explained solely by electronic charge transfer but also involves a modulation of rigidity. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  19. Hendra and Nipah viruses: why are they so deadly?

    Science.gov (United States)

    Marsh, Glenn A; Wang, Lin-Fa

    2012-06-01

    Henipavirus, including Hendra and Nipah viruses, is a group of emerging bat-borne paramyxoviruses which were responsible for severe disease outbreaks in humans, horses and pigs. The mortality rate of human infection varies between 50 and 100%, making them one of the most deadly viruses known to infect humans. Its use of highly conserved cell surface molecules (ephrin) as entry receptors and its highly effective replication and fusion strategies are believed to be important characteristics responsible for its high pathogenicity. Henipavirus also encodes multiple accessory proteins which play a key role in evasion of host innate immune responses. Our recent study on the mechanism of IFN antagonism by henipaviruses indicated that a better understanding of the virus-host interaction provides great potential to develop new therapeutic strategies against these viruses. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  20. Voronoi Diagrams Without Bounding Boxes

    Science.gov (United States)

    Sang, E. T. K.

    2015-10-01

    We present a technique for presenting geographic data in Voronoi diagrams without having to specify a bounding box. The method restricts Voronoi cells to points within a user-defined distance of the data points. The mathematical foundation of the approach is presented as well. The cell clipping method is particularly useful for presenting geographic data that is spread in an irregular way over a map, as for example the Dutch dialect data displayed in Figure 2. The automatic generation of reasonable cell boundaries also makes redundant a frequently used solution to this problem that requires data owners to specify region boundaries, as in Goebl (2010) and Nerbonne et al (2011).

  1. Hot cells and glove boxes

    International Nuclear Information System (INIS)

    1992-05-01

    Hot cells and glove boxes have been designed and developed to conduct operations involving radioactive materials which require some degree of manipulation. Glove boxes were developed to manipulate alpha emitters. As their name indicates, these are airtight boxes usually constructed with transparent, see-through walls. Operations are conducted inside by means of gloves or mechanic manipulators. These boxes are also used for biological-protection purposes, e.g., manipulation of viruses or similar applications. Basically, hot cells are used for: - radioisotope fractionning and purification; - post-irradiation studies, and - tests or sundry operations involving radiological or biological protection. These shielded cells are constructed on a supporting structure made out of steel and antimonious Pb bricks with airtight inner enclosures and lead-glass windows. Operations are conducted by means of remote telemanipulators. Airtight enclosures are made out of a stainless steel structure forming an Omega-shaped profile on the openings which are fitted with acrylic panels. Tight-proof insulation is achieved by means of appropriate joints placed between the structure and acrylic plates. Electric passage ducts for fluids or electrical conductors also preserve absolute hermeticity. The partition enclosures are placed on supporting tables made out of normalized sections and steel plates. If needed, enclosures, may be removed and replaced by others. For materials-transference purposes, these cells are provided with shielded doors, air-tight doors and a connecting duct between the tight-proof enclosures with a guillotine-type gate and a pneumatic remote-control coupling/uncoupling system. Each work post is provided with an operations console and a control cabinet with depression indicating manometers, input inlet valves and electrical interconnecting boards. A desk-type console centralizes operation commands which will take place inside the enclosures. Appropriate lighting has been

  2. Comet 'Bites the Dust' Around Dead Star

    Science.gov (United States)

    2006-01-01

    [figure removed for brevity, see original site] Infrared Spectrometer Graph This artist's concept illustrates a comet being torn to shreds around a dead star, or white dwarf, called G29-38. NASA's Spitzer Space Telescope observed a cloud of dust around this white dwarf that may have been generated from this type of comet disruption. The findings suggest that a host of other comet survivors may still orbit in this long-dead solar system. The white dwarf G29-38 began life as a star that was about three times as massive as our sun. Its death involved the same steps that the sun will ultimately undergo billions of years from now. According to theory, the G29-38 star became brighter and brighter as it aged, until it bloated up into a dying star called a red giant. This red giant was large enough to engulf and evaporate any terrestrial planets like Earth that happened to be in its way. Later, the red giant shed its outer atmosphere, leaving behind a shrunken skeleton of star, called a white dwarf. If the star did host a planetary system, outer planets akin to Jupiter and Neptune and a remote ring of icy comets would remain. The Spitzer observations provide observational evidence for this orbiting outpost of comet survivors. Astronomers speculate that one such comet was knocked into the inner regions of G29-38, possibly by an outer planet. As the comet approached very close to the white dwarf, it may have been torn apart by the star's tidal forces. Eventually, all that would be left of the comet is a disk of dust. This illustration shows a comet in the process of being pulverized: part of it still exists as a chain of small clumps, while the rest has already spread out into a dusty disk. Comet Shoemaker-Levy 9 broke apart in a similar fashion when it plunged into Jupiter in 1994. Evidence for Comets Found in Dead Star's Dust The graph of data, or spectrum, from NASA's Spitzer Space Telescope indicates that a dead star, or white dwarf, called G29-38, is shrouded by a cloud

  3. [A case of lycanthropy with deadly violence].

    Science.gov (United States)

    Bénézech, M; De Witte, J; Etchepare, J J; Bourgeois, M

    1989-01-01

    After a short historical review of the contemporary medical literature, the authors analyze a new and original observation of lycanthropy. He is a 28 years old man, imprisoned for deadly violence, who has been showing, for many years, the belief of being transformed into a werewolf during depersonalization episodes when he presents a lycanthropic behaviour. Our observation is closer to hysteria and mythomania on an antisocial personality, although it seems difficult to place the mental pathology of this alcoholic recidivist delinquent into a nosographical frame.

  4. Simplified Dead Reckoning on a Tortuous Path

    Science.gov (United States)

    Robertson, David

    An approximation procedure is described, which greatly simplifies dead reckoning on a tortuous path. The journey is divided into N segments of equal length, L. The overall direction is approximately the average direction of the segments. The net distance is approximately NL[1-var() is the variance (in radians squared) of bearings, 7. Propagation of random errors is discussed. In a case study in sub-tropical rainforest the technique gives an estimated position whose associated circle of 68% confidence has a radius of about 10% of the net distance.

  5. De Plein Fouet: Is Strategy Dead?

    Science.gov (United States)

    2015-06-01

    discuss strategy. Judging by the title you chose, I assume you have a point of view.Richard Szafranski (RS): Yes, sir . Le tir de plein fouet is one of...quarters, neither strategic thinking nor strategy is dead in the NGA. RS: I’m not sure that what you’re describing, sir , is a strategy as much as it is the...correcting like a self-driving car . I don’t see that coming, or coming very soon, though. Remember, we exist because we support people in harm’s way

  6. Box graphs and singular fibers

    International Nuclear Information System (INIS)

    Hayashi, Hirotaka; Lawrie, Craig; Morrison, David R.; Schäfer-Nameki, Sakura

    2014-01-01

    We determine the higher codimension fibers of elliptically fibered Calabi-Yau fourfolds with section by studying the three-dimensional N=2 supersymmetric gauge theory with matter which describes the low energy effective theory of M-theory compactified on the associated Weierstrass model, a singular model of the fourfold. Each phase of the Coulomb branch of this theory corresponds to a particular resolution of the Weierstrass model, and we show that these have a concise description in terms of decorated box graphs based on the representation graph of the matter multiplets, or alternatively by a class of convex paths on said graph. Transitions between phases have a simple interpretation as “flopping' of the path, and in the geometry correspond to actual flop transitions. This description of the phases enables us to enumerate and determine the entire network between them, with various matter representations for all reductive Lie groups. Furthermore, we observe that each network of phases carries the structure of a (quasi-)minuscule representation of a specific Lie algebra. Interpreted from a geometric point of view, this analysis determines the generators of the cone of effective curves as well as the network of flop transitions between crepant resolutions of singular elliptic Calabi-Yau fourfolds. From the box graphs we determine all fiber types in codimensions two and three, and we find new, non-Kodaira, fiber types for E 6 , E 7 and E 8

  7. Forkhead box transcription factors in embryonic heart development and congenital heart disease.

    Science.gov (United States)

    Zhu, Hong

    2016-01-01

    Embryonic heart development is a very complicated process regulated precisely by a network composed of many genes and signaling pathways in time and space. Forkhead box (Fox, FOX) proteins are a family of transcription factors characterized by the presence of an evolutionary conserved "forkhead"or "winged-helix" DNA-binding domain and able to organize temporal and spatial gene expression during development. They are involved in a wide variety of cellular processes, such as cell cycle progression, proliferation, differentiation, migration, metabolism and DNA damage response. An abundance of studies in model organisms and systems has established that Foxa2, Foxc1/c2, Foxh1 and Foxm1, Foxos and Foxps are important components of the signaling pathways that instruct cardiogenesis and embryonic heart development, playing paramount roles in heart development. The previous studies also have demonstrated that mutations in some of the forkhead box genes and the aberrant expression of forkhead box gene are heavily implicated in the congenital heart disease (CHD) of humans. This review primarily focuses on the current understanding of heart development regulated by forkhead box transcription factors and molecular genetic mechanisms by which forkhead box factors modulate heart development during embryogenesis and organogenesis. This review also summarizes human CHD related mutations in forkhead box genes as well as the abnormal expression of forkhead box gene, and discusses additional possible regulatory mechanisms of the forkhead box genes during embryonic heart development that warrant further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Lessons from the light-cone box

    CERN Document Server

    Leibbrandt, G

    2000-01-01

    Working in the noncovariant light-cone gauge, we discuss the explicit computation of the 1PI four-point function ("box diagram") in Yang- Mills theory. The complete box diagram which consists of 16 box subdiagrams, 8 lynx subdiagrams and 4 fish subdiagrams, yields both local and nonlocal UV divergent terms. The nonlocal terms are consistent with gauge symmetry and correspond to a nonlocal renormalization of the wave function. (14 refs).

  9. When the dead are alive! The influence of the living dead in the letter of Jude

    Directory of Open Access Journals (Sweden)

    Stephan J. Joubert

    2002-12-01

    Full Text Available This essay investigates the impact of the deceased on  the audience to which the letter of Jude was originally addressed. A construct of the influence of the “living dead” in ancient Babylon, Israel, the Graeco-Roman world and in African tradition serves as a basic cognitive map to come to terms with Jude’s views on the dead. It is argued that, since the wicked dead, who are being physically punished in  the underworld,  are kept alive  in the collective memory of Jude’s community and since their deeds are re-enacted in the sinful behavior  of intruders in their midst, their lives are influenced by  the “presence” of these living dead. On the other hand and, although Jude does not deal with the physical whereabouts of the righteous death, he and his readers know that their postmortem honour is still intact. The righteous in this community is assured that God protects the integrity of the faithful dead.

  10. Ethics of practicing medical procedures on newly dead and nearly dead patients.

    Science.gov (United States)

    Berger, Jeffrey T; Rosner, Fred; Cassell, Eric J

    2002-10-01

    To examine the ethical issues raised by physicians performing, for skill development, medically nonindicated invasive medical procedures on newly dead and dying patients. Literature review; issue analysis employing current normative ethical obligations, and evaluation against moral rules and utilitarian assessments manifest in other common perimortem practices. Practicing medical procedures for training purposes is not uncommon among physicians in training. However, empiric information is limited or absent evaluating the effects of this practice on physician competence and ethics, assessing public attitudes toward practicing medical procedures and requirements for consent, and discerning the effects of a consent requirement on physicians' clinical competence. Despite these informational gaps, there is an obligation to secure consent for training activities on newly and nearly dead patients based on contemporary norms for informed consent and family respect. Paradigms of consent-dependent societal benefits elsewhere in health care support our determination that the benefits from physicians practicing procedures does not justify setting aside the informed consent requirement. Current ethical norms do not support the practice of using newly and nearly dead patients for training in invasive medical procedures absent prior consent by the patient or contemporaneous surrogate consent. Performing an appropriately consented training procedure is ethically acceptable when done under competent supervision and with appropriate professional decorum. The ethics of training on the newly and nearly dead remains an insufficiently examined area of medical training.

  11. Uterus retrieval process from brain dead donors.

    Science.gov (United States)

    Gauthier, Tristan; Piver, Pascal; Pichon, Nicolas; Bibes, Romain; Guillaudeau, Angelique; Piccardo, Alessandro; Pesteil, Francis; Tricard, Jeremy; Gardet, Emmanuel; Laskar, Marc; Lalloué, Fabrice; Marquet, Pierre; Aubard, Yves

    2014-08-01

    To describe the feasibility of human uterus retrieval after donation after brain death. Single-center, prospective study. University hospital. Female brain dead donors. The families of female brain dead donors were informed about consent to uterus donation. A specific organ retrieval procedure was performed. At the end of the procedure the uterus was removed together with the hypogastric vessels, parametria, and vaginal fornix. The tolerance of the uterus to cold ischemia was evaluated with histology and TUNEL reaction up to 24 hours. Rate of uterus donation refusal. Between August 1, 2012 and July 31, 2013, seven uteri were retrieved from 14 female multiorgan donors. No refusal to uterus donation occurred. Our surgical protocol did not interfere with vital organ retrieval and was readily accepted by the other transplantation teams. The hypogastric vessels could be preserved in all cases but for one vein loss in the first retrieval. Histology studies did not find major morphologic changes after 24 hours of cold ischemia. Apoptosis was rare. Uterus retrieval could be part of a reproducible multiorgan procurement procedure. Uterus donation seems readily accepted. This preliminary study is a necessary step before any transplantation project. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Breathing Life Into Dead-Zones

    Directory of Open Access Journals (Sweden)

    Gressel Oliver

    2013-04-01

    Full Text Available The terrestrial planet formation regions of protoplanetary disks are generally sufficiently cold to be con- sidered non-magnetized and, consequently, dynamically inactive. However, recent investigations of these so-called “Dead-Zones” indicate the possibility that disks with strong mean radial temperature gradients can support instabilities associated with disk-normal gradients of the basic Keplerian shear profile. This process, known as the Goldreich-Schubert-Fricke (GSF instability, is the instability of short radial wavelength inertial modes and depends wholly on the presence of vertical gradients of the mean Keplerian (zonal flow. We report here high resolution fully nonlinear axisymmetric numerical studies of this instability and find a number of features including how, in the nonlinear saturated state, unstable discs become globally distorted, with strong vertical oscillations occurring at all radii due to local instability. We find that nonaxisymmetric numerical experiments are accompanied by significant amounts angular momentum transport (α ~ 0001. This instability should be operating in the Dead-Zones of protoplanetary disks at radii greater than 10-15 AU in minimum mass solar nebula models.

  13. Repackaging SRS Black Box TRU Waste

    International Nuclear Information System (INIS)

    Swale, D. J.; Stone, K.A.; Milner, T. N.

    2006-01-01

    Historically, large items of TRU Waste, which were too large to be packaged in drums for disposal have been packaged in various sizes of custom made plywood boxes at the Savannah River Site (SRS), for many years. These boxes were subsequently packaged into large steel ''Black Boxes'' for storage at SRS, pending availability of Characterization and Certification capability, to facilitate disposal of larger items of TRU Waste. There are approximately 107 Black Boxes in inventory at SRS, each measuring some 18' x 12' x 7', and weighing up to 45,000 lbs. These Black Boxes have been stored since the early 1980s. The project to repackage this waste into Standard Large Boxes (SLBs), Standard Waste Boxes (SWB) and Ten Drum Overpacks (TDOP), for subsequent characterization and WIPP disposal, commenced in FY04. To date, 10 Black Boxes have been repackaged, resulting in 40 SLB-2's, and 37 B25 overpack boxes, these B25's will be overpacked in SLB-2's prior to shipping to WIPP. This paper will describe experience to date from this project

  14. The three-box paradox revisited

    International Nuclear Information System (INIS)

    Ravon, Tamar; Vaidman, Lev

    2007-01-01

    The classical three-box paradox of Kirkpatrick (2003 J. Phys. A: Math. Gen. 36 4891) is compared to the original quantum three-box paradox of Aharonov and Vaidman (1991 J. Phys. A: Math. Gen. 24 2315). It is argued that the quantum three-box experiment is a 'quantum paradox' in the sense that it is an example of a classical task which cannot be accomplished using classical means, but can be accomplished using quantum devices. It is shown that Kirkpatrick's card game is analogous to a different game with a particle in three boxes which does not contain paradoxical features

  15. A new G-M counter dead time model

    International Nuclear Information System (INIS)

    Lee, S.H.; Gardner, R.P.

    2000-01-01

    A hybrid G-M counter dead time model was derived by combining the idealized paralyzable and non-paralyzable models. The new model involves two parameters, which are the paralyzable and non-paralyzable dead times. The dead times used in the model are very closely related to the physical dead time of the G-M tube and its resolving time. To check the validity of the model, the decaying source method with 56 Mn was used. The corrected counting rates by the new G-M dead time model were compared with the observed counting rates obtained from the measurement and gave very good agreement within 5% up to 7x10 4 counts/s for a G-M tube with a dead time of about 300 μs

  16. IMPROVED, FAVORABLE FOR ENVIRONMENT POLYURETHANE COLD-BOX-PROCESS (COLD BOX «HUTTENES-ALBERTUS» .

    Directory of Open Access Journals (Sweden)

    A. Sergini

    2005-01-01

    Full Text Available The results of the laboratory and industrial investigations, the purpose of which is improvement of the classical Cold-box-process, i.e. the process of the slugs hardening in cold boxes, are presented.

  17. Photographic Study Of A Dead-Pressed Explosive

    Science.gov (United States)

    Swallowe, G. M.; Field, J. E.

    1983-03-01

    High speed photography in conjunction with electron microscopy and a pressure measuring technique have been used to investigate the differences between dead-pressed and non-dead-pressed samples of the primary explosive Mercury Fulminate (Hg Ful). Photographs of reaction propagation were taken in transmitted light using a specially adapted drop-weight machine with transparent anvils. The results of these experiments suggested a mechanism for dead-pressing in Hg Ful based on the microscopic internal structure of the compacted explosive.

  18. EFSA Panel on Biological Hazards (BIOHAZ); Scientific Opinion on Composting on-farm of dead poultry

    DEFF Research Database (Denmark)

    Hald, Tine

    EFSA’s Scientific Panel on Biological Hazards (BIOHAZ) was asked for a scientific opinion on two alternative methods for processing Category (Cat) 2 Animal By-Products (ABP). The material to be treated consists of poultry manure, straw and dead-on-farm poultry; this implies that the animals died...... due to a disease, which in most cases was not properly diagnosed. The proposed processes are composting methods to be used on-farm. The first method is a continuous open system where composting is done under roof in piles separated by wooden partition walls. The piles are processed without enforced...... aeration. The second method is a discontinuous closed system consisting of two different types of containers (Box-Compost®) coupled with a device for conditioning temperature and humidity during composting (Compostronic®). The end-product obtained is intended to be used as an organic fertiliser. According...

  19. A novel ethylene-responsive factor from Tamarix hispida, ThERF1, is a GCC-box- and DRE-motif binding protein that negatively modulates abiotic stress tolerance in Arabidopsis.

    Science.gov (United States)

    Wang, Liuqiang; Qin, Liping; Liu, Wenjin; Zhang, Daoyuan; Wang, Yucheng

    2014-09-01

    Ethylene-responsive factor (ERF) family is one of the largest families of plant-specific transcription factor that can positively or negatively regulate abiotic stress tolerance. However, their functions in regulating abiotic stress tolerance are still not fully understood. In this study, we characterized the functions of an ERF gene from Tamarix hispida, ThERF1, which can negatively regulate abiotic stress tolerance. The expression of ThERF1 was induced by salinity, PEG-simulated drought and abscisic acid (ABA) treatments. ThERF1 can specifically bind to GCC-box and DRE motifs. Overexpression of ThERF1 in transgenic Arabidopsis plants showed inhibited seed germination, and decreased fresh weight gain and root growth compared with wild-type (WT) plants. In addition, the transcript levels of several superoxide dismutase (SOD) and peroxidase (POD) genes in transgenic plants were significantly inhibited compared with in WT plants, resulting in decreased SOD and POD activities in transgenic plants under salt and drought stress conditions. Furthermore, the reactive oxygen species (ROS) levels, malondialdehyde (MDA) contents and cell membrane damage in ThERF1-transformed plants were all highly increased relative to WT plants. Our results suggest that ThERF1 negatively regulates abiotic stress tolerance by strongly inhibiting the expression of SOD and POD genes, leading to decreased ROS-scavenging ability. © 2014 Scandinavian Plant Physiology Society.

  20. VORONOI DIAGRAMS WITHOUT BOUNDING BOXES

    Directory of Open Access Journals (Sweden)

    E. T. K. Sang

    2015-10-01

    Full Text Available We present a technique for presenting geographic data in Voronoi diagrams without having to specify a bounding box. The method restricts Voronoi cells to points within a user-defined distance of the data points. The mathematical foundation of the approach is presented as well. The cell clipping method is particularly useful for presenting geographic data that is spread in an irregular way over a map, as for example the Dutch dialect data displayed in Figure 2. The automatic generation of reasonable cell boundaries also makes redundant a frequently used solution to this problem that requires data owners to specify region boundaries, as in Goebl (2010 and Nerbonne et al (2011.

  1. Respect for the dead and the ethics of anatomy.

    Science.gov (United States)

    Wilkinson, T M

    2014-04-01

    Dead bodies are not persons but nor are they just things. What, ethically speaking, do the living owe the dead when it comes to using their bodies in anatomy? The article begins with the general question of respect for the dead. It distinguishes between why we should respect the dead, how we should respect them, and the weight to be given to respect. It sets out an account of the reason to respect the dead based on their interests. The article then turns to how the dead should be respected and the importance of doing so. Specifically, it considers three ethical issues in anatomy: the role of the family, the use of unclaimed bodies, and the public display of bodies donated for that purpose. This article claims that what it is to respect the dead is substantially determined by their wishes. Nonetheless the article argues that respect is consistent with allowing the family to veto anatomical use even when the deceased has consented because respect for the dead does not require following all their possible wishes. Respect is also consistent with using unclaimed bodies to which no one--deceased or family--has consented because the interests of the dead do not directly require consent and the interests of the family are unlikely to be relevant. Finally, the article does not see anything disrespectful in the public display of the bodies of those who have consented. Copyright © 2013 Wiley Periodicals, Inc.

  2. Genome-wide analysis of the SBP-box gene family in Chinese cabbage (Brassica rapa subsp. pekinensis).

    Science.gov (United States)

    Tan, Hua-Wei; Song, Xiao-Ming; Duan, Wei-Ke; Wang, Yan; Hou, Xi-Lin

    2015-11-01

    The SQUAMOSA PROMOTER BINDING PROTEIN (SBP)-box gene family contains highly conserved plant-specific transcription factors that play an important role in plant development, especially in flowering. Chinese cabbage (Brassica rapa subsp. pekinensis) is a leafy vegetable grown worldwide and is used as a model crop for research in genome duplication. The present study aimed to characterize the SBP-box transcription factor genes in Chinese cabbage. Twenty-nine SBP-box genes were identified in the Chinese cabbage genome and classified into six groups. We identified 23 orthologous and 5 co-orthologous SBP-box gene pairs between Chinese cabbage and Arabidopsis. An interaction network among these genes was constructed. Sixteen SBP-box genes were expressed more abundantly in flowers than in other tissues, suggesting their involvement in flowering. We show that the MiR156/157 family members may regulate the coding regions or 3'-UTR regions of Chinese cabbage SBP-box genes. As SBP-box genes were found to potentially participate in some plant development pathways, quantitative real-time PCR analysis was performed and showed that Chinese cabbage SBP-box genes were also sensitive to the exogenous hormones methyl jasmonic acid and salicylic acid. The SBP-box genes have undergone gene duplication and loss, evolving a more refined regulation for diverse stimulation in plant tissues. Our comprehensive genome-wide analysis provides insights into the SBP-box gene family of Chinese cabbage.

  3. Electrical requirements for unshielded glove boxes

    International Nuclear Information System (INIS)

    1978-02-01

    The specification relates to the general design and installation of electrical services required in unshielded glove boxes in which atmospheres of air, argon or nitrogen etc. may exist either temporarily or permanently. The specification does not apply to electrical services for glove boxes with flammable explosive atmospheres. (author)

  4. A boxing procedure for corrected cast impressions.

    Science.gov (United States)

    Ansari, I H

    1994-01-01

    This new method for boxing a corrected cast impression for a distal extension removable partial denture improves the procedure. The framework with its impression is seated on the remainder of the cast after anatomic ridges have been removed and luted with sticky wax, and the assembly is inserted into a previously formed thermoplastic box and poured to make a new corrected cast.

  5. High-Mobility Group Box-1 Protein Mediates the Regulation of Signal Transducer and Activator of Transcription-3 in the Diabetic Retina and in Human Retinal Müller Cells.

    Science.gov (United States)

    Mohammad, Ghulam; Jomar, Deema; Siddiquei, Mohammad Mairaj; Alam, Kaiser; Abu El-Asrar, Ahmed M

    2017-01-01

    The expression of high-mobility group box-1 (HMGB1) and signal transducer and activator of transcription-3 (STAT-3) is upregulated in the diabetic retina. We hypothesized that the activation of STAT-3 is under the control of HMGB1. Retinas from 1-month-old diabetic rats and from normal rats intravitreally injected with HMGB1 and human retinal Müller glial cells (MIO-M1) stimulated with HMGB1 or high glucose were studied by Western blot analysis and immunofluorescence. We also studied the effect of the HMGB1 inhibitor glycyrrhizin (GA) on high-glucose-induced pSTAT-3 nuclear translocation and upregulation in Müller cells and on pSTAT-3 expression in the retinas of diabetic rats (n = 7-10 in each group). In addition, we studied the effect of STAT-3 inhibitor on the HMGB1-induced induction of vascular endothelial growth factor (VEGF) by Müller cells and human retinal microvascular endothelial cell (HRMEC) migration. Treatment of retinal Müller cells with recombinant HMGB1 induced nuclear translocation of pSTAT-3 but did not alter pSTAT-3 expression. High glucose induced a significant upregulation of HMGB1 and pSTAT-3 upregulation and nuclear translocation in retinal Müller cells. GA co-treatment normalized the high-glucose-induced upregulation of HMGB1 and pSTAT-3 upregulation and nuclear translocation in Müller cells. Intravitreal administration of HMGB1 in normal and diabetic rats upregulated pSTAT-3 expression in the retina. GA attenuated the diabetes-induced upregulation of pSTAT-3 in the retina. The STAT-3 inhibitor attenuated HMGB1-induced VEGF upregulation by Müller cells and HRMEC migration. The results suggest a role for HMGB1 in the modulation of STAT-3 expression in the diabetic retina. © 2016 S. Karger AG, Basel.

  6. 49 CFR 178.515 - Standards for reconstituted wood boxes.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Standards for reconstituted wood boxes. 178.515... wood boxes. (a) The identification code for a reconstituted wood box is 4F. (b) Construction requirements for reconstituted wood boxes are as follows: (1) The walls of boxes must be made of water...

  7. North American box turtles: A natural history

    Science.gov (United States)

    Dodd, C. Kenneth

    2002-01-01

    Once a familiar backyard visitor in many parts of the United States and Mexico, the box turtle is losing the battle against extinction. In North American Box Turtles, C. Kenneth Dodd, Jr., has written the first book-length natural history of the twelve species and subspecies of this endangered animal. This volume includes comprehensive information on the species’ evolution, behavior, courtship and reproduction, habitat use, diet, population structure, systematics, and disease. Special features include color photos of all species, subspecies, and their habitats; a simple identification guide to both living and fossil species; and a summary of information on fossil Terrapene and Native uses of box turtles. End-of-chapter sections highlight future research directions, including the need for long-term monitoring and observation of box turtles within their natural habitat and conservation applications. A glossary and a bibliography of literature on box turtles accompany the text.

  8. Genomic Organization, Phylogenetic Comparison and Differential Expression of the SBP-Box Family Genes in Grape

    Science.gov (United States)

    Hou, Hongmin; Li, Jun; Gao, Min; Singer, Stacy D.; Wang, Hao; Mao, Linyong; Fei, Zhangjun; Wang, Xiping

    2013-01-01

    Background The SBP-box gene family is specific to plants and encodes a class of zinc finger-containing transcription factors with a broad range of functions. Although SBP-box genes have been identified in numerous plants including green algae, moss, silver birch, snapdragon, Arabidopsis, rice and maize, there is little information concerning SBP-box genes, or the corresponding miR156/157, function in grapevine. Methodology/Principal Findings Eighteen SBP-box gene family members were identified in Vitis vinifera, twelve of which bore sequences that were complementary to miRNA156/157. Phylogenetic reconstruction demonstrated that plant SBP-domain proteins could be classified into seven subgroups, with the V. vinifera SBP-domain proteins being more closely related to SBP-domain proteins from dicotyledonous angiosperms than those from monocotyledonous angiosperms. In addition, synteny analysis between grape and Arabidopsis demonstrated that homologs of several grape SBP genes were found in corresponding syntenic blocks of Arabidopsis. Expression analysis of the grape SBP-box genes in various organs and at different stages of fruit development in V. quinquangularis ‘Shang-24’ revealed distinct spatiotemporal patterns. While the majority of the grape SBP-box genes lacking a miR156/157 target site were expressed ubiquitously and constitutively, most genes bearing a miR156/157 target site exhibited distinct expression patterns, possibly due to the inhibitory role of the microRNA. Furthermore, microarray data mining and quantitative real-time RT-PCR analysis identified several grape SBP-box genes that are potentially involved in the defense against biotic and abiotic stresses. Conclusion The results presented here provide a further understanding of SBP-box gene function in plants, and yields additional insights into the mechanism of stress management in grape, which may have important implications for the future success of this crop. PMID:23527172

  9. Dead bacteria reverse antibiotic-induced host defense impairment in burns.

    Science.gov (United States)

    Chen, Lee-Wei; Chen, Pei-Hsuan; Fung, Chang-Phone; Hsu, Ching-Mei

    2014-10-01

    Burn patients can incur high rates of hospital-acquired infections. The mechanism of antibiotic exposure on inducing infection vulnerability has not been determined. This study aimed to examine the effects of antibiotic treatment on host defense mechanisms. First we treated C57/BL6 mice with combined antibiotic treatment after 30% to 35% total body surface area burn. Animals were sacrificed at 48 hours after sham or thermal injury treatment. Bacterial counts in intestinal lumen and mucosa were measured. Next, we treated animals with or without oral dead Escherichia coli or Staphylococcus aureus supplementation to stimulate Toll-like receptor in the intestinal mucosa. Toll-like receptor 4, antibacterial protein expression, nuclear factor (NF)-κB DNA-binding activity, and bacteria-killing activity in the intestinal mucosa; intestinal permeability; bacterial translocation to mesenteric lymph nodes; Klebsiella pneumoniae translocation; interleukin-6 in the blood; and phagocytic activity of alveolar macrophages, were assessed. Thermal injury increased microflora and NF-κB DNA-binding activity of the intestine. Systemic antibiotic treatment decreased gut microflora and increased bacterial translocation to mesenteric lymph nodes, intestinal permeability, and interleukin-6 levels in the blood. Antibiotic treatment also decreased bacteria-killing activity in intestinal mucosa and phagocytic activity of alveolar macrophages. Oral dead E coli and S aureus supplementation induced NF-κB DNA-binding activity, Toll-like receptor 4, and antibacterial protein expression of the intestinal mucosa. Taken together with the fact that dead bacteria reversed antibiotic-induced K pneumoniae translocation and intestinal and pulmonary defense impairment, we conclude that combined antibiotic treatment results in systemic host defense impairment in burns through the decrease in intestinal flora. We suggest that dead bacteria supplementation could induce nondefensin protein expression and

  10. Crystal structure of the UBR-box from UBR6/FBXO11 reveals domain swapping mediated by zinc binding.

    Science.gov (United States)

    Muñoz-Escobar, Juliana; Kozlov, Guennadi; Gehring, Kalle

    2017-10-01

    The UBR-box is a 70-residue zinc finger domain present in the UBR family of E3 ubiquitin ligases that directly binds N-terminal degradation signals in substrate proteins. UBR6, also called FBXO11, is an UBR-box containing E3 ubiquitin ligase that does not bind N-terminal signals. Here, we present the crystal structure of the UBR-box domain from human UBR6. The dimeric crystal structure reveals a unique form of domain swapping mediated by zinc coordination, where three independent protein chains come together to regenerate the topology of the monomeric UBR-box fold. Analysis of the structure suggests that the absence of N-terminal residue binding arises from the lack of an amino acid binding pocket. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  11. Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Larsen, Steen; Helge, Jørn Wulff

    2013-01-01

    signaling. We investigated this by two weeks of oral metformin treatment of muscle specific kinase dead a(2) (KD) AMPK mice and wild type (WT) littermates. We measured mitochondrial respiration and protein activity and expressions of key enzymes involved in mitochondrial carbohydrate and fat metabolism...

  12. Dead time corrections using the backward extrapolation method

    Energy Technology Data Exchange (ETDEWEB)

    Gilad, E., E-mail: gilade@bgu.ac.il [The Unit of Nuclear Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105 (Israel); Dubi, C. [Department of Physics, Nuclear Research Center NEGEV (NRCN), Beer-Sheva 84190 (Israel); Geslot, B.; Blaise, P. [DEN/CAD/DER/SPEx/LPE, CEA Cadarache, Saint-Paul-les-Durance 13108 (France); Kolin, A. [Department of Physics, Nuclear Research Center NEGEV (NRCN), Beer-Sheva 84190 (Israel)

    2017-05-11

    Dead time losses in neutron detection, caused by both the detector and the electronics dead time, is a highly nonlinear effect, known to create high biasing in physical experiments as the power grows over a certain threshold, up to total saturation of the detector system. Analytic modeling of the dead time losses is a highly complicated task due to the different nature of the dead time in the different components of the monitoring system (e.g., paralyzing vs. non paralyzing), and the stochastic nature of the fission chains. In the present study, a new technique is introduced for dead time corrections on the sampled Count Per Second (CPS), based on backward extrapolation of the losses, created by increasingly growing artificially imposed dead time on the data, back to zero. The method has been implemented on actual neutron noise measurements carried out in the MINERVE zero power reactor, demonstrating high accuracy (of 1–2%) in restoring the corrected count rate. - Highlights: • A new method for dead time corrections is introduced and experimentally validated. • The method does not depend on any prior calibration nor assumes any specific model. • Different dead times are imposed on the signal and the losses are extrapolated to zero. • The method is implemented and validated using neutron measurements from the MINERVE. • Result show very good correspondence to empirical results.

  13. 10 CFR 1047.7 - Use of deadly force.

    Science.gov (United States)

    2010-01-01

    ... explosives). (3) Nuclear weapons or nuclear explosive devices. When deadly force reasonably appears to be necessary to prevent the theft, sabotage, or unauthorized control of a nuclear weapon or nuclear explosive device. (4) Special nuclear material. When deadly force reasonably appears to be necessary to prevent the...

  14. Recipe for Hypoxia: Playing the Dead Zone Game

    Science.gov (United States)

    Kastler, Jessica A.

    2009-01-01

    Dead zones--areas experiencing low levels of dissolved oxygen--are growing in shallow ocean waters around the world. Research has shown that dead zones form as a result of a specific type of pollution, called nutrient enrichment or eutrophication, and are found in almost every coastal zone where humans have large populations. Concepts related to…

  15. Dead wood inventory and assessment in South Korea

    Science.gov (United States)

    Jong-Su Yim; Rae Hyun Kim; Sun-Jeong Lee; Yeongmo. Son

    2015-01-01

    Dead wood (DW) plays a critical role not only in maintaining biodiversity but also in stocking carbon under UNFCCC. From the 5th national forest inventory (NFI5; 2006-2010) in South Korea, field data relevant to the DW including standing and downed dead trees by four decay class, etc. were collected. Based on the NFI5 data,...

  16. Quantifying carbon stores and decomposition in dead wood: A review

    Science.gov (United States)

    Matthew B. Russell; Shawn Fraver; Tuomas Aakala; Jeffrey H. Gove; Christopher W. Woodall; Anthony W. D’Amato; Mark J. Ducey

    2015-01-01

    The amount and dynamics of forest dead wood (both standing and downed) has been quantified by a variety of approaches throughout the forest science and ecology literature. Differences in the sampling and quantification of dead wood can lead to differences in our understanding of forests and their role in the sequestration and emissions of CO2, as...

  17. Cascades of pile-up and dead time

    International Nuclear Information System (INIS)

    Pomme, S.

    2008-01-01

    Count loss through a cascade of pile-up and dead time is studied. Time interval density-distribution functions and throughput factors are presented for counters with a series arrangement of pile-up and extending or non-extending dead time. A counter is considered, where an artificial dead time is imposed on every counted event, in order to control the length and type of dead time. For such a system, it is relatively easy to determine an average count-loss correction factor via a live-time clock gated by the imposed dead-time signal ('live-time mode'), or otherwise to apply a correction factor based on the inversion of the throughput function ('real-time mode'). However, these techniques do not account for additional loss through pulse pile-up. In this work, counting errors associated with neglecting cascade effects are calculated for measurements in live-time and real-time mode

  18. Cellular microRNAs up-regulate transcription via interaction with promoter TATA-box motifs.

    Science.gov (United States)

    Zhang, Yijun; Fan, Miaomiao; Zhang, Xue; Huang, Feng; Wu, Kang; Zhang, Junsong; Liu, Jun; Huang, Zhuoqiong; Luo, Haihua; Tao, Liang; Zhang, Hui

    2014-12-01

    The TATA box represents one of the most prevalent core promoters where the pre-initiation complexes (PICs) for gene transcription are assembled. This assembly is crucial for transcription initiation and well regulated. Here we show that some cellular microRNAs (miRNAs) are associated with RNA polymerase II (Pol II) and TATA box-binding protein (TBP) in human peripheral blood mononuclear cells (PBMCs). Among them, let-7i sequence specifically binds to the TATA-box motif of interleukin-2 (IL-2) gene and elevates IL-2 mRNA and protein production in CD4(+) T-lymphocytes in vitro and in vivo. Through direct interaction with the TATA-box motif, let-7i facilitates the PIC assembly and transcription initiation of IL-2 promoter. Several other cellular miRNAs, such as mir-138, mir-92a or mir-181d, also enhance the promoter activities via binding to the TATA-box motifs of insulin, calcitonin or c-myc, respectively. In agreement with the finding that an HIV-1-encoded miRNA could enhance viral replication through targeting the viral promoter TATA-box motif, our data demonstrate that the interaction with core transcription machinery is a novel mechanism for miRNAs to regulate gene expression. © 2014 Zhang et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  19. Genetics Home Reference: lysinuric protein intolerance

    Science.gov (United States)

    ... Home Health Conditions Lysinuric protein intolerance Lysinuric protein intolerance Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Lysinuric protein intolerance is a disorder caused by the body's inability ...

  20. No Time for Dead Time: Use the Fourier Amplitude Differences to Normalize Dead-time-affected Periodograms

    Science.gov (United States)

    Bachetti, Matteo; Huppenkothen, Daniela

    2018-02-01

    Dead time affects many of the instruments used in X-ray astronomy, by producing a strong distortion in power density spectra. This can make it difficult to model the aperiodic variability of the source or look for quasi-periodic oscillations. Whereas in some instruments a simple a priori correction for dead-time-affected power spectra is possible, this is not the case for others such as NuSTAR, where the dead time is non-constant and long (∼2.5 ms). Bachetti et al. (2015) suggested the cospectrum obtained from light curves of independent detectors within the same instrument as a possible way out, but this solution has always only been a partial one: the measured rms was still affected by dead time because the width of the power distribution of the cospectrum was modulated by dead time in a frequency-dependent way. In this Letter, we suggest a new, powerful method to normalize dead-time-affected cospectra and power density spectra. Our approach uses the difference of the Fourier amplitudes from two independent detectors to characterize and filter out the effect of dead time. This method is crucially important for the accurate modeling of periodograms derived from instruments affected by dead time on board current missions like NuSTAR and Astrosat, but also future missions such as IXPE.

  1. Black-Box Gastrointestinal Tract—Needs and Prospects of Gaining Insights of Fate of Fat, Protein, and Starch in Case of Exocrine Pancreatic Insufficiency by Using Fistulated Pigs

    Science.gov (United States)

    Mößeler, Anne; Kamphues, Josef

    2017-01-01

    Exocrine pancreatic insufficiency (EPI) results in the maldigestion and malabsorption of nutrients. The digestive processes in humans and other monogastric species like rat and pig are characterized by a predominantly enzymatic digestion within the small intestine and microbial fermentation located in the hindgut. For protein, it is doctrine that only prececally absorbed amino acids can be transferred to the amino acid pool of the host, while postileal absorption of nitrogen-containing compounds occurs mainly in the form of ammonia, being a burden rather than a benefit for the organism. The pig is an established animal model for humans to study digestive processes. As digestion is markedly impaired in case of EPI the use of an appropriate animal model to study the effects of this disease and to optimize treatment and dietetic measures is of special interest. By using an animal model of experimentally-induced EPI allowing differentiating between digestive processes in the small as well as in the large intestine by use of ileo-cecal fistulated animals, marked effects of EPI on prececal digestion of starch and protein could be shown. The data indicate that estimation of digestibility of nutrients over the entire digestive tract results in a distinct overestimation of enzymatic digestion of starch and protein. Therefore, this model clearly shows that protein and starch digestion are significantly reduced in case of EPI although this cannot be detected on a fecal level. As postileal fermentation of starch is associated not only with energy losses but also with intensive gas production, this is of special interest to minimize meteorism and improve wellbeing of patients. PMID:28212351

  2. Micro-facies of Dead Sea sediments

    Science.gov (United States)

    Neugebauer, Ina; Schwab, Markus J.; Brauer, Achim; Frank, Ute; Dulski, Peter; Kitagawa, Hiroyuki; Enzel, Yehouda; Waldmann, Nicolas; Ariztegui, Daniel; Drilling Party, Dsddp

    2013-04-01

    Lacustrine sediments infilling the Dead Sea basin (DSB) provide a rare opportunity to trace changing climates in the eastern Mediterranean-Levant region throughout the Pleistocene and Holocene. In this context, high-resolution investigation of changes in sediment micro- facies allow deciphering short-term climatic fluctuations and changing environmental conditions in the Levant. The Dead Sea is a terminal lake with one of the largest drainage areas in the Levant, located in the Mediterranean climate zone and influenced also by the Saharo-Arabian deserts. Due to drastic climatic changes in this region, an exceptionally large variety of lacustrine sediments has been deposited in the DSB. These sediments, partially the results of changing lake levels, primarily represent changes in precipitation (e.g. Enzel et al., 2008). Evaporites (halite and gypsum) reflect dry climatic conditions during interglacials, while alternated aragonite-detritus (AAD) is deposited during glacial lake level high-stands. Here we present the first micro-facies inventory of a ~450 m long sediment profile from the deepest part of the northern DSB (ICDP site 5017-1, ~300 m water depth). The sediment record comprises the last two glacial-interglacial cycles, with mainly AAD facies in the upper part of the Amora Formation (penultimate glacial) and the last glacial Lisan Formation. The last interglacial Samra and the Holocene Zeelim Formations are predominantly characterized by thick bedded halite deposits, intercalated by partly laminated detrital marl sequences. Representative sections of the different facies types have been analyzed for micro-facies on petrographic thin sections, supported by high-resolution µXRF element scanning, magnetic susceptibility measurements and microscopic fluorescence analysis. Furthermore, Holocene sediments retrieved at the deep basin core site have been compared to their shallow-water counterpart at the western margin of the lake (core DSEn; Migowski et al., 2004

  3. MADS-box gene evolution - structure and transcription patterns

    DEFF Research Database (Denmark)

    Johansen, Bo; Pedersen, Louise Buchholt; Skipper, Martin

    2002-01-01

    Mads-box genes, ABC model, Evolution, Phylogeny, Transcription patterns, Gene structure, Conserved motifs......Mads-box genes, ABC model, Evolution, Phylogeny, Transcription patterns, Gene structure, Conserved motifs...

  4. A Conserved Metal Binding Motif in the Bacillus subtilis Competence Protein ComFA Enhances Transformation.

    Science.gov (United States)

    Chilton, Scott S; Falbel, Tanya G; Hromada, Susan; Burton, Briana M

    2017-08-01

    Genetic competence is a process in which cells are able to take up DNA from their environment, resulting in horizontal gene transfer, a major mechanism for generating diversity in bacteria. Many bacteria carry homologs of the central DNA uptake machinery that has been well characterized in Bacillus subtilis It has been postulated that the B. subtilis competence helicase ComFA belongs to the DEAD box family of helicases/translocases. Here, we made a series of mutants to analyze conserved amino acid motifs in several regions of B. subtilis ComFA. First, we confirmed that ComFA activity requires amino acid residues conserved among the DEAD box helicases, and second, we show that a zinc finger-like motif consisting of four cysteines is required for efficient transformation. Each cysteine in the motif is important, and mutation of at least two of the cysteines dramatically reduces transformation efficiency. Further, combining multiple cysteine mutations with the helicase mutations shows an additive phenotype. Our results suggest that the helicase and metal binding functions are two distinct activities important for ComFA function during transformation. IMPORTANCE ComFA is a highly conserved protein that has a role in DNA uptake during natural competence, a mechanism for horizontal gene transfer observed in many bacteria. Investigation of the details of the DNA uptake mechanism is important for understanding the ways in which bacteria gain new traits from their environment, such as drug resistance. To dissect the role of ComFA in the DNA uptake machinery, we introduced point mutations into several motifs in the protein sequence. We demonstrate that several amino acid motifs conserved among ComFA proteins are important for efficient transformation. This report is the first to demonstrate the functional requirement of an amino-terminal cysteine motif in ComFA. Copyright © 2017 American Society for Microbiology.

  5. Personal Identity and Resurrection from the Dead

    Directory of Open Access Journals (Sweden)

    Gasparov Igor

    2017-04-01

    Full Text Available The paper examines arguments of the “Christian materialist” Trenton Merricks that he provided in support of the claim that the Christian doctrine of resurrection from the dead is compatible with the materialist understanding of the nature of human beings. In his paper The Resurrection of the Body, Merricks discussed two aspects of the materialist interpretation of the traditional religious doctrine of the bodily resurrection. On the one hand, he analyses and tries to overcome objections against the possibility of the general resurrection in case the materialist understanding of the nature of human personality should be true (mainly the problem of the temporal gap. On the other hand, he provides some reasons why the materialist understanding of human nature is more relevant than its dualist counterpart to the doctrine of the bodily resurrection. The present paper evaluates his arguments and discusses the suggestion that the doctrine of resurrection is not only compatible with materialism, but is also tenable if human beings are identical with their physical bodies. The conclusion of the paper is that Merricks’ apologetic arguments achieve their aims in defending the doctrine of resurrection only partially; the resurrection doctrine appears more tenable if we accept the dualistic conception of human nature.

  6. Autopsies of the real: Resurrecting the dead

    Directory of Open Access Journals (Sweden)

    Valis, Noël

    2011-12-01

    Full Text Available The sense of the real, or the material—the dead body—as an inextricable part of the sacred does not disappear in the secular environment of the nineteenth and twentieth centuries. This article analyzes specific humanitarian narratives centered on the practice of autopsy and mummification, in which the traces of Catholicism act as a kind of spectral discourse of the imagination, where the real is configured in forms of the uncanny, the monstrous or the sacred.

    El sentido de lo real, de lo material —el cuerpo sin vida— como una inextricable parte de lo sagrado, no desaparece del ambiente secular de los siglos XIX y XX. En los relatos analizados en este artículo se estudia cómo en determinadas narrativas humanitarias centradas en la práctica de la autopsia y la momificación, las huellas del catolicismo actúan como una suerte de discurso espectral de la imaginación, en que lo real se configura en formas de lo siniestro, lo monstruoso o lo sagrado.

  7. Fault-tolerant dead reckoning system for a modular vehicle

    Science.gov (United States)

    Hashimoto, Masafumi; Oba, Fuminori; Takahashi, Kazuhiko

    2005-12-01

    A fault-tolerant dead reckoning system is presented for a modular vehicle, which consists of one chassis unit and several wheel units. The units locally estimate the vehicle position based on their own internal sensors. The local estimates are exchanged among the units via an inter-communication system, and they are fused in a decentralized manner. The units can then determine the vehicle position accurately. The decentralized dead reckoning algorithm is formulated based on the information filter and the covariance Intersection method. For enhancing the reliability of the dead reckoning a multi-model based fault detection and diagnosis (FDD) of the internal sensors is incorporated into the dead reckoning system. The units diagnose their sensors with the FDD system, and they apply only the normal sensors for the vehicle localization. In this paper two fault modes (hard fault and noise fault modes) of the sensors are handled; on the hard fault the sensor output is stuck at a constant value. On the noise fault it is disturbed by a large noise. The FDD algorithm is based on the variable structure interacting multiple-model estimator. The fault-tolerant dead reckoning algorithm was implemented on our indoor test-vehicle, which consists of one chassis unit and four wheel units. Experimental results show that our dead reckoning provided better localization accuracy than the conventional one (i.e., the dead reckoning without sensor FDD system) did even though the sensors partially failed.

  8. Packing a cake into a box

    KAUST Repository

    Skopenkov, Mikhail

    2011-05-01

    Given a triangular cake and a box in the shape of its mirror image, how can the cake be cut into a minimal number of pieces so that it can be put into the box? The cake has icing, so we are not allowed to put it into the box upside down. V. G. Boltyansky asked this question in 1977 and showed that three pieces always suffice. In this paper we provide examples of cakes that cannot be cut into two pieces to be put into the box. This shows that three is the answer to Boltyansky\\'s question. We also give examples of cakes which can be cut into two pieces. © THE MATHEMATICAL ASSOCIATION OF AMERICA.

  9. Spacer for supporting fuel element boxes

    International Nuclear Information System (INIS)

    Wild, E.

    1979-01-01

    A spacer plate unit arranged externally on each side and at a predetermined level of a polygonal fuel element box for mutually supporting, with respect to one another, a plurality of the fuel element boxes forming a fuel element bundle, is formed of a first and a second spacer plate part each having the same length and the same width and being constituted of unlike first and second materials, respectively. The first and second spacer plate parts of the several spacer plate units situated at the predetermined level are arranged in an alternating continuous series when viewed in the peripheral direction of the fuel element box, so that any two spacer plate units belonging to face-to-face oriented sides of two adjoining fuel element boxes in the fuel element bundle define interfaces of unlike materials

  10. Glove boxes. Dimensions and requirements. Draft

    International Nuclear Information System (INIS)

    1985-07-01

    The standard is to be applied to work done in glove-boxes, whereby either the personnel need to be protected from the damaging effects of the materials being handled, or the materials from the effects of the environment. It is to be applied to glove-boxes in which substances are handled which emit ionising radiation (radioactive substances). This norm is not restricted to glove-boxes in which processes are carried out on a technique scale. In accordance with this norm, only those pressures and temperatures are allowed to be present in the glove-boxes, that do not offer significantly from the work areas. Alongside the stipulations of this standard regard is also always to be taken of the regulations in the radiation protection ordinance. (orig./HP) [de

  11. Cosmetic Foot Surgery: Fashion's Pandora's Box

    Science.gov (United States)

    ... A A A | Print | Share Cosmetic Foot Surgery: Fashion’s Pandora’s Box? Foot and ankle surgeons warn against ... a "face lift" and fit them into high-fashion shoes. But physician members of the American College ...

  12. Black-Box Search by Unbiased Variation

    DEFF Research Database (Denmark)

    Lehre, Per Kristian; Witt, Carsten

    2012-01-01

    The complexity theory for black-box algorithms, introduced by Droste, Jansen, and Wegener (Theory Comput. Syst. 39:525–544, 2006), describes common limits on the efficiency of a broad class of randomised search heuristics. There is an obvious trade-off between the generality of the black-box model...... and the strength of the bounds that can be proven in such a model. In particular, the original black-box model provides for well-known benchmark problems relatively small lower bounds, which seem unrealistic in certain cases and are typically not met by popular search heuristics.In this paper, we introduce a more...... restricted black-box model for optimisation of pseudo-Boolean functions which we claim captures the working principles of many randomised search heuristics including simulated annealing, evolutionary algorithms, randomised local search, and others. The key concept worked out is an unbiased variation operator...

  13. ENERGY STAR Certified Set Top Boxes

    Data.gov (United States)

    U.S. Environmental Protection Agency — Certified models meet all ENERGY STAR requirements as listed in the Version 5.1 ENERGY STAR Program Requirements for Set-top Boxes that are effective as of January...

  14. A Lithium Vapor Box Divertor Similarity Experiment

    Science.gov (United States)

    Cohen, Robert A.; Emdee, Eric D.; Goldston, Robert J.; Jaworski, Michael A.; Schwartz, Jacob A.

    2017-10-01

    A lithium vapor box divertor offers an alternate means of managing the extreme power density of divertor plasmas by leveraging gaseous lithium to volumetrically extract power. The vapor box divertor is a baffled slot with liquid lithium coated walls held at temperatures which increase toward the divertor floor. The resulting vapor pressure differential drives gaseous lithium from hotter chambers into cooler ones, where the lithium condenses and returns. A similarity experiment was devised to investigate the advantages offered by a vapor box divertor design. We discuss the design, construction, and early findings of the vapor box divertor experiment including vapor can construction, power transfer calculations, joint integrity tests, and thermocouple data logging. Heat redistribution of an incident plasma-based heat flux from a typical linear plasma device is also presented. This work supported by DOE Contract No. DE-AC02-09CH11466 and The Princeton Environmental Institute.

  15. DEAD-Box RNA Helicases are among the Constituents of the Tobacco Pollen mRNA Storing Bodies

    Czech Academy of Sciences Publication Activity Database

    Hafidh, Said; Potěšil, D.; Zdráhal, Z.; Honys, David

    2013-01-01

    Roč. 1, č. 3 (2013) ISSN 2329-9029 R&D Projects: GA ČR GPP501/11/P321; GA ČR(CZ) GAP501/11/1462; GA MŠk(CZ) ED1.1.00/02.0068; GA MŠk(CZ) LD13049 Institutional support: RVO:61389030 Keywords : Translation * mRNA storage * RNA helicase Subject RIV: EB - Genetics ; Molecular Biology

  16. Weld Residual Stress in Corner Boxing Joints

    OpenAIRE

    Kazuyoshi, Matsuoka; Tokuharu, Yoshii; Ship Research Institute, Ministry of Transport; Ship Research Institute, Ministry of Transport

    1998-01-01

    Fatigue damage often occurs in corner boxing welded joints because of stress concentration and residual stress. The hot spot stress approach is applicable to stress concentration. However, the number of suitable methods for estimating residual stress in welded joints is limited. The purpose of this paper is to clarify the residual stress in corner boxing joints. The method of estimating residual stresses based on the inherent stress technique is presented. Residual stress measurements are per...

  17. MADS-box genes and crop domestication: the jack of all traits.

    Science.gov (United States)

    Schilling, Susanne; Pan, Sirui; Kennedy, Alice; Melzer, Rainer

    2018-03-24

    MADS-box genes are key regulators of virtually every aspect of plant reproductive development. They play especially prominent roles in flowering time control, inflorescence architecture, floral organ identity determination, and seed development. The developmental and evolutionary importance of MADS-box genes is widely acknowledged. However, their role during flowering plant domestication is less well recognized. Here, we provide an overview illustrating that MADS-box genes have been important targets of selection during crop domestication and improvement. Numerous examples from a diversity of crop plants show that various developmental processes have been shaped by allelic variations in MADS-box genes. We propose that new genomic and genome editing resources provide an excellent starting point for further harnessing the potential of MADS-box genes to improve a variety of reproductive traits in crops. We also suggest that the biophysics of MADS-domain protein-protein and protein-DNA interactions, which is becoming increasingly well characterized, makes them especially suited to exploit coding sequence variations for targeted breeding approaches.

  18. Dead-Time Generation in Six-Phase Frequency Inverter

    Directory of Open Access Journals (Sweden)

    Aurelijus Pitrėnas

    2016-06-01

    Full Text Available In this paper control of multi-phase induction drives is discussed. Structure of six-phase frequency inverter is examined. The article deals with dead-time generation circuits in six-phase frequency inverter for transistor control signals. Computer models of dead-time circuits is created using LTspice software package. Simulation results are compared with experimental results of the tested dead-time circuits. Parameters obtained in simulation results are close to the parameters obtained in experimental results.

  19. Adaptive control with variable dead-zone nonlinearities

    Science.gov (United States)

    Orlicki, D.; Valavani, L.; Athans, M.; Stein, G.

    1984-01-01

    It has been found that fixed error dead-zones as defined in the existing literature result in serious degradation of performance, due to the conservativeness which characterizes the determination of their width. In the present paper, variable width dead-zones are derived for the adaptive control of plants with unmodeled dynamics. The derivation makes use of information available about the unmodeled dynamics both a priori as well as during the adaptation process, so as to stabilize the adaptive loop and at the same time overcome the conservativeness and performance limitations of fixed-dead zone adaptive or fixed gain controllers.

  20. Are We the Walking Dead? Burnout as Zombie Apocalypse

    Science.gov (United States)

    Doolittle, Benjamin R.

    2016-01-01

    The Walking Dead, one of the most popular television shows in recent history, uses the plot of a zombie apocalypse as a lens into exploring the human condition. Amidst a particularly dangerous moment, the show’s hero references the human struggle to survive by remarking, “We are the walking dead.” This offhand comment sheds light upon physicians’ struggles in medicine, in particular the high prevalence of burnout and the challenge to cultivate compassion and meaning. This is an important question for our age and for our profession. Are we the walking dead? PMID:28376445

  1. HYDROGEN AND VOC RETENTION IN WASTE BOXES

    Energy Technology Data Exchange (ETDEWEB)

    PACE ME; MARUSICH RM

    2008-11-21

    The Hanford Waste Management Project Master Documented Safety Analysis (MDSA) (HNF-14741, 2003) identifies derived safety controls to prevent or mitigate the risks of a single-container deflagration during operations requiring moving, venting or opening transuranic (TRU)-waste containers. The issue is whether these safety controls are necessary for operations involving TRU-waste boxes that are being retrieved from burial at the Hanford Site. This paper investigates the potential for a deflagration hazard within these boxes and whether safety controls identified for drum deflagration hazards should be applied to operations involving these boxes. The study evaluates the accumulation of hydrogen and VOCs within the waste box and the transport of these gases and vapors out of the waste box. To perform the analysis, there were numerous and major assumptions made regarding the generation rate and the transport pathway dimensions and their number. Since there is little actual data with regards to these assumptions, analyses of three potential configurations were performed to obtain some indication of the bounds of the issue (the concentration of hydrogen or flammable VOCs within a waste box). A brief description of each of the three cases along with the results of the analysis is summarized.

  2. Molecular dissection of the APC/C inhibitor Rca1 shows a novel F-box-dependent function.

    Science.gov (United States)

    Zielke, Norman; Querings, Silvia; Grosskortenhaus, Ruth; Reis, Tânia; Sprenger, Frank

    2006-12-01

    Rca1 (regulator of Cyclin A)/Emi (early mitotic inhibitor) proteins are essential inhibitors of the anaphase-promoting complex/cyclosome (APC/C). In Drosophila, Rca1 is required during G2 to prevent premature cyclin degradation by the Fizzy-related (Fzr)-dependent APC/C activity. Here, we present a structure and function analysis of Rca1 showing that a carboxy-terminal fragment is sufficient for APC/C inhibition. Rca1/Emi proteins contain a conserved F-box and interact with components of the Skp-Cullin-F-box (SCF) complex. So far, no function has been ascribed to this domain. We find that the F-box of Rca1 is dispensable for APC/C-Fzr inhibition during G2. Nevertheless, we show that Rca1 has an additional function at the G1-S transition, which requires the F-box. Overexpression of Rca1 accelerates the G1-S transition in an F-box-dependent manner. Conversely, S-phase entry is delayed in cells in which endogenous Rca1 is replaced by a transgene lacking the F-box. We propose that Rca1 acts as an F-box protein in an as yet uncharacterized SCF complex, which promotes S-phase entry.

  3. Groundwater-Lake Interaction in the Dead Sea Area

    Science.gov (United States)

    Kiro, Y.; Weinstein, Y.; Starinsky, A.; Yechieli, Y.

    2011-12-01

    The Dead Sea hypersaline water system is unique in terms of its unusual geochemical composition, rapid lake level changes and water composition of the brines discharging along its shoreline. The Dead Sea can be used as a natural lab for studying groundwater-seawater interaction and saline water hydrological circulation along the aquifer-sea boundary. It provides an opportunity to follow the geochemical processes along a flow path from the lake into the aquifer and back into the lake. The lake level has been dropping since the 1960's due to human interference in its water budget, reaching a rate of 1 m/yr in recent years. Saline water circulation in coastal aquifers may be a major process that governs trace element mass balances in coastal areas. This study uses radium isotopes in order to quantify the lake water circulation in the Dead Sea aquifer. There are four naturally-occurring radium isotopes, with half-lives ranging from 3.7 days to 1600 years which are chain products of uranium and thorium isotopes. Radium isotopes are usually enriched in saline groundwater and therefore are good candidates for estimating seawater or hypersaline lake water circulation in the aquifer. Compared to most natural water bodies, the Dead Sea is extremely enriched in radium and barium, where both 226Ra and 228Ra activities and Ba concentration (145, 1-2 dpm/L and 5 mg/L, respectively) are 2-3 orders of magnitude higher than in ocean water, whereas the salinity of the Dead Sea is only 10 times higher. Circulated Dead Sea water in the aquifer contains decreased concentrations of 226Ra (60 dpm/L), Ba (1.5 mg/L), Sr (300 relative to 340 mg/L in the Dead Sea) and Sulfate (250 relative to 392 mg/L). We suggest that the low 226Ra and Ba concentrations are due to precipitation of barite and celestine from the supersaturated Dead Sea water on entering the aquifer. 228Ra and the shorter-lived 224Ra and 223Ra, which have much lower activities in the Dead Sea (up to 1.8, 3 and 0.8 dpm

  4. Probable Carbonate Fossilization Processes Within Dead Sea Microbial Remains

    Science.gov (United States)

    Morris, P. A.; Wentworth, S. J.; Thomas-Keprta, K. L.; Allen, C. C.; McKay, D. S.

    2001-01-01

    Microbial fossilization processes in the Dead Sea is primarily associated with the calcium cation. The putative fossilized microbes do not represent the reported living microbial population. Additional information is contained in the original extended abstract.

  5. Dead zone area at the downstream flow of barrages

    Directory of Open Access Journals (Sweden)

    Mohamed F. Sauida

    2016-12-01

    Full Text Available Flow separation is a natural phenomenon encountered at some cases downstream of barrages. The main flow is divided into current and dead zone flows. The percentage area of dead zone flow must be taken into consideration downstream of barrages, due to its negative effect on flow characteristics. Experimental studies were conducted in the Hydraulic Research Institute (HRI, on a physical regulator model with five vents. Theoretically the separation zone is described as a part of an ellipse which is practically verified by plotting velocity vectors. The results show that the percentage area of dead zone to the area through length of separation depends mainly on the expansion ratio [channel width to width of opened vents], with maximum value of 81% for operated side gates. A statistical analysis was derived, to predict the percentage area of dead zone flow to the area through length of separation.

  6. In the Event of Bioterrorism: Protecting Families from Deadly Diseases

    Science.gov (United States)

    ... Español Text Size Email Print Share In the Event of Bioterrorism: Protecting Families from Deadly Diseases Page ... exposure. Talking to Children about Bioterrorism In the event of bioterrorism, knowing how to talk to your ...

  7. 49 CFR 230.101 - Steam locomotive driving journal boxes.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Steam locomotive driving journal boxes. 230.101... Locomotives and Tenders Running Gear § 230.101 Steam locomotive driving journal boxes. (a) Driving journal boxes. Driving journal boxes shall be maintained in a safe and suitable condition for service. Not more...

  8. 49 CFR 178.517 - Standards for plastic boxes.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Standards for plastic boxes. 178.517 Section 178... PACKAGINGS Non-bulk Performance-Oriented Packaging Standards § 178.517 Standards for plastic boxes. (a) The following are identification codes for plastic boxes: (1) 4H1 for an expanded plastic box; and (2) 4H2 for a...

  9. SNPs in the HIV-1 TATA box and the AIDS pandemic.

    Science.gov (United States)

    Suslov, Valentin V; Ponomarenko, Petr M; Efimov, Vadim M; Savinkova, Ludmila K; Ponomarenko, Mikhail P; Kolchanov, Nikolay A

    2010-06-01

    Evolutionary trends have been examined in 146 HIV-1 forms (2662 copies, 2311 isolates) polymorphic for the TATA box using the "DNA sequence-->affinity for TBP" regression (TBP is the TATA binding protein). As a result, a statistically significant excess of low-affinity TATA box HIV-1 variants corresponding to a low level of both basal and TAT-dependent expression and, consequently, slow replication of HIV-1 have been detected. A detailed analysis revealed that the excess of slowly replicating HIV-1 is associated with the subtype E-associated TATA box core sequence "CATAAAA". Principal Component Analysis performed on 2662 HIV-1 TATA box copies in 70 countries revealed the presence of two principal components, PC1 (75.7% of the variance) and PC2 (23.3% of the variance). They indicate that each of these countries is specifically associated with one of the following trends in HIV-1 evolution: neutral drift around the normal TATA box; neutral drift around the slowly replicating TATA box core sequence (phylogenetic inertia); an adaptive increase in the frequency of the slowly replicating form.

  10. Management of the dead in Tacloban City after Typhoon Haiyan

    OpenAIRE

    Julius Erving Ballera; Vikki Carr de los Reyes; Ma Nemia Sucaldito; Alethea De Guzman; Luis Sy, Jr; Ma Justina Zapanta; Ferchito Avelino; Joselito Feliciano; Enrique Tayag

    2015-01-01

    Introduction: The post-disaster management of the dead involves a series of steps including on-site identification, transfer, storage and examination of bodies and delivery to families for burial. Two weeks after Typhoon Haiyan, a team from the Department of Health (DOH) was tasked with identifying the dead in Tacloban City. Methods: A suitable site for the collection of bodies was identified and an algorithm and standard data collection form developed. The retrieval of bodies was coordi...

  11. The dead donor rule, voluntary active euthanasia, and capital punishment.

    Science.gov (United States)

    Coons, Christian; Levin, Noah

    2011-06-01

    We argue that the dead donor rule, which states that multiple vital organs should only be taken from dead patients, is justified neither in principle nor in practice. We use a thought experiment and a guiding assumption in the literature about the justification of moral principles to undermine the theoretical justification for the rule. We then offer two real world analogues to this thought experiment, voluntary active euthanasia and capital punishment, and argue that the moral permissibility of terminating any patient through the removal of vital organs cannot turn on whether or not the practice violates the dead donor rule. Next, we consider practical justifications for the dead donor rule. Specifically, we consider whether there are compelling reasons to promulgate the rule even though its corresponding moral principle is not theoretically justified. We argue that there are no such reasons. In fact, we argue that promulgating the rule may actually decrease public trust in organ procurement procedures and medical institutions generally - even in states that do not permit capital punishment or voluntary active euthanasia. Finally, we examine our case against the dead donor rule in the light of common arguments for it. We find that these arguments are often misplaced - they do not support the dead donor rule. Instead, they support the quite different rule that patients should not be killed for their vital organs.

  12. Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1) Mutation and TRAP1 Inhibitor Gamitrinib-triphenylphosphonium (G-TPP) Induce a Forkhead Box O (FOXO)-dependent Cell Protective Signal from Mitochondria.

    Science.gov (United States)

    Kim, Hyunjin; Yang, Jinsung; Kim, Min Ju; Choi, Sekyu; Chung, Ju-Ryung; Kim, Jong-Min; Yoo, Young Hyun; Chung, Jongkyeong; Koh, Hyongjong

    2016-01-22

    TRAP1 (tumor necrosis factor receptor-associated protein 1), a mitochondrial Hsp90 family chaperone, has been identified as a critical regulator of cell survival and bioenergetics in tumor cells. To discover novel signaling networks regulated by TRAP1, we generated Drosophila TRAP1 mutants. The mutants successfully developed into adults and produced fertile progeny, showing that TRAP1 is dispensable in development and reproduction. Surprisingly, mutation or knockdown of TRAP1 markedly enhanced Drosophila survival under oxidative stress. Moreover, TRAP1 mutation ameliorated mitochondrial dysfunction and dopaminergic (DA) neuron loss induced by deletion of a familial Parkinson disease gene PINK1 (Pten-induced kinase 1) in Drosophila. Gamitrinib-triphenylphosphonium, a mitochondria-targeted Hsp90 inhibitor that increases cell death in HeLa and MCF7 cells, consistently inhibited cell death induced by oxidative stress and mitochondrial dysfunction induced by PINK1 mutation in mouse embryonic fibroblast cells and DA cell models such as SH-SY5Y and SN4741 cells. Additionally, gamitrinib-triphenylphosphonium also suppressed the defective locomotive activity and DA neuron loss in Drosophila PINK1 null mutants. In further genetic analyses, we showed enhanced expression of Thor, a downstream target gene of transcription factor FOXO, in TRAP1 mutants. Furthermore, deletion of FOXO almost nullified the protective roles of TRAP1 mutation against oxidative stress and PINK1 mutation. These results strongly suggest that inhibition of the mitochondrial chaperone TRAP1 generates a retrograde cell protective signal from mitochondria to the nucleus in a FOXO-dependent manner. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Exercising is like flogging a dead horse

    International Nuclear Information System (INIS)

    Molhoek, W.

    2003-01-01

    - FR (NPP Gravelines) was conducted (22-23th of May 2001). The main objectives of the INEX series of exercises were focused on: decision making based on limited information and uncertain plant conditions; the use of real time communications with actual equipment and procedures; public information and interaction with media; the use of real weather for real time forecasts. For real further improvement of (nuclear) emergency management and response, not only national and international exercises such as INEX, CONVEX, JINEX etc. are needed, but the efforts to improve personal performance of key-persons involved is crucial. Structural plans to train and exercise individuals and teams should therefore be developed as well. To move the dead horse and create a racehorse need a lot of personal skills and attention. It is also recognized that often the carrot is better than the whip. (author)

  14. Hemoadsorption of high-mobility-group box 1 using a porous polymethylmethacrylate fiber in a swine acute liver failure model.

    Science.gov (United States)

    Amemiya, Ryusuke; Shinoda, Masahiro; Yamada, Masayuki; Ueno, Yoshiyuki; Shimada, Kaoru; Fujieda, Hiroaki; Yagi, Hiroshi; Mizota, Takamasa; Nishiyama, Ryo; Oshima, Go; Yamada, Shingo; Matsubara, Kentaro; Abe, Yuta; Hibi, Taizo; Kitago, Minoru; Obara, Hideaki; Itano, Osamu; Kitagawa, Yuko

    2018-04-01

    High-mobility-group box chromosomal protein 1 has been identified as an important mediator of various kinds of acute and chronic inflammation. In this study, we aimed to develop a column that effectively adsorbs high-mobility-group box chromosomal protein 1 by altering the pore size of the fiber. First, we produced three types of porous polymethylmethacrylate fiber by altering the concentration of polymethylmethacrylate dissolved in dimethylsulfoxide. We then selected a fiber based on the results of an in vitro incubation test of high-mobility-group box chromosomal protein 1 adsorption. Using the selected fiber, we constructed a new column and tested its high-mobility-group box chromosomal protein 1 adsorption capacity during 4-h extracorporeal hemoperfusion in a swine acute liver failure model. Electron microscope observation showed that the three types of fibers had different pore sizes on the surface and in cross section, which were dependent on the concentration of polymethylmethacrylate. In the in vitro incubation test, fiber with moderate-sized pores demonstrated the highest adsorption capacity. In the in vivo hemoperfusion study, the ratio of the high-mobility-group box chromosomal protein 1 concentration at the outlet versus the inlet of the column was significantly lower with the new column than with the control column during 4-h extracorporeal hemoperfusion. The normalized plasma level of high-mobility-group box chromosomal protein 1 at 12 h after the completion of hemoperfusion was significantly lower with the new column than with the control column. The newly developed polymethylmethacrylate column adsorbs high-mobility-group box chromosomal protein 1 during hemoperfusion in swine ALF model.

  15. High mobility group box 1 skews macrophage polarization and negatively influences phagocytosis of apoptotic cells

    NARCIS (Netherlands)

    Schaper, Fleur; de Leeuw, Karina; Horst, Geesje; Bootsma, Hendrika; Limburg, Pieter C.; Heeringa, Peter; Bijl, Marc; Westra, Johanna

    2016-01-01

    OBJECTIVES: Decreased phagocytosis of apoptotic cells plays an important role in the pathogenesis of SLE. This can lead to secondary necrosis and release of nuclear proteins, such as high mobility group box 1 (HMGB1). We hypothesized that increased HMGB1 levels, as present in SLE, skew macrophage

  16. The archaeal TFIIE homologue facilitates transcription initiation by enhancing TATA-box recognition

    NARCIS (Netherlands)

    Bell, S.D.; Brinkman, A.B.; Oost, van der J.; Jackson, S.P.

    2001-01-01

    Transcription from many archaeal promoters can be reconstituted in vitro using recombinant TATA-box binding protein (TBP) and transcription factor B (TFB)—homologues of eukaryal TBP and TFIIB—together with purified RNA polymerase (RNAP). However, all archaeal genomes sequenced to date reveal the

  17. Forkhead-box transcription factors and their role in the immune system

    NARCIS (Netherlands)

    Coffer, PJ; Burgering, BMT

    2004-01-01

    It is more than a decade since the discovery of the first forkhead-box (FOX) transcription factor in the fruit fly Drosophila melanogaster. In the intervening time, there has been an explosion in the identification and characterization of members of this family of proteins. Importantly, in the past

  18. Changes in position and quality of preferred nest box: effects on nest box use by laying hens

    DEFF Research Database (Denmark)

    Riber, Anja Brinch; Nielsen, Birte L.

    2013-01-01

    Using laying hens, we investigated whether position of a nest box, both within the pen and relative to other nest boxes, influenced the preference for a nest box, and how a sudden and marked change to the preferred box influenced the use of nest boxes by the hens. Groups (n=12) of 15 Isa Warren...... hens were housed in pens, each with five identical nest boxes in different positions: Two single (in a corner or not) and a triplet of nest boxes (one of which in a corner). The use of nest boxes was determined by the number of eggs laid daily in each box. Three experiments, each lasting 10 days, were...... carried out. First, the undisturbed use of each of the nest box types was investigated, and a strong preference (Peggs laid there. Second, each of the hen groups was moved to another pen allocated at random, and where...

  19. Molecular and phylogenetic analyses of the complete MADS-box transcription factor family in Arabidopsis: New openings to the MADS World

    NARCIS (Netherlands)

    Parenicova, L.; Folter, de S.; Kieffer, M.; Horner, D.S.; Favalli, C.; Busscher, J.; Cook, H.E.; Ingram, R.M.; Kater, M.M.; Davies, B.; Angenent, G.C.; Colombo, L.

    2003-01-01

    MADS-box transcription factors are key regulators of several plant development processes. Analysis of the complete Arabidopsis genome sequence revealed 107 genes encoding MADS-box proteins, of which 84re of unknown function. Here, we provide a complete overview of this family, describing the gene

  20. Accumulation of transcription factors and cell signaling-related proteins in the nucleus during citrus-Xanthomonas interaction.

    Science.gov (United States)

    Rani, T Swaroopa; Durgeshwar, P; Podile, Appa Rao

    2015-07-20

    The nucleus is the maestro of the cell and is involved in the modulation of cell signaling during stress. We performed a comprehensive nuclear proteome analysis of Citrus sinensis during interaction with host (Xanthomonas citri pv. citri-Xcc) and non-host (Xanthomonas oryzae pv. oryzae-Xoo) pathogens. The nuclear proteome was obtained using a sequential method of organelle enrichment and determined by nano-LC-MS/MS analysis. A total of 243 proteins accumulated differentially during citrus-Xanthomonas interaction, belonging to 11 functional groups, with signaling and transcription-related proteins dominating. MADS-box transcription factors, DEAD-box RNA helicase and leucine aminopeptidase, mainly involved in jasmonic acid (JA) responses, were in high abundance during non-host interaction (Xoo). Signaling-related proteins like serine/threonine kinase, histones (H3.2, H2A), phosphoglycerate kinase, dynamin, actin and aldolase showed increased accumulation early during Xoo interaction. Our results suggest that there is a possible involvement of JA-triggered defense responses during non-host resistance, with early recognition of the non-host pathogen. Copyright © 2015. Published by Elsevier GmbH.

  1. Advances in the theory of box integrals

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, David H.; Borwein, J.M.; Crandall, R.E.

    2009-06-25

    Box integrals - expectations <|{rvec r}|{sup s}> or <|{rvec r}-{rvec q}|{sup s}> over the unit n-cube (or n-box) - have over three decades been occasionally given closed forms for isolated n,s. By employing experimental mathematics together with a new, global analytic strategy, we prove that for n {le} 4 dimensions the box integrals are for any integer s hypergeometrically closed in a sense we clarify herein. For n = 5 dimensions, we show that a single unresolved integral we call K{sub 5} stands in the way of such hyperclosure proofs. We supply a compendium of exemplary closed forms that naturally arise algorithmically from this theory.

  2. Grey Box Modelling of Hydrological Systems

    DEFF Research Database (Denmark)

    Thordarson, Fannar Ørn

    The main topic of the thesis is grey box modelling of hydrologic systems, as well as formulation and assessment of their embedded uncertainties. Grey box model is a combination of a white box model, a physically-based model that is traditionally formulated using deterministic ordinary differential...... the lack of fit in state space formulation, and further support decisions for a model expansion. By using stochastic differential equations to formulate the dynamics of the hydrological system, either the complexity of the model can be increased by including the necessary hydrological processes...... in the model, or formulation of process noise can be considered so that it meets the physical limits of the hydrological system and give an adequate description of the embedded uncertainty in model structure. The thesis consists of two parts: a summary report and a part which contains six scientific papers...

  3. Options for reducing HIV transmission related to the dead space in needles and syringes.

    Science.gov (United States)

    Zule, William A; Pande, Poonam G; Otiashvili, David; Bobashev, Georgiy V; Friedman, Samuel R; Gyarmathy, V Anna; Des Jarlais, Don C

    2018-01-15

    When shared by people who inject drugs, needles and syringes with different dead space may affect the probability of HIV and hepatitis C virus (HCV) transmission differently. We measured dead space in 56 needle and syringe combinations obtained from needle and syringe programs across 17 countries in Europe and Asia. We also calculated the amounts of blood and HIV that would remain in different combinations following injection and rinsing. Syringe barrel capacities ranged from 0.5 to 20 mL. Needles ranged in length from 8 to 38 mm. The average dead space was 3 μL in low dead space syringes with permanently attached needles, 13 μL in high dead space syringes with low dead space needles, 45 μL in low dead space syringes with high dead space needles, and 99 μL in high dead space syringes with high dead space needles. Among low dead space designs, calculated volumes of blood and HIV viral burden were lowest for low dead space syringes with permanently attached needles and highest for low dead space syringes with high dead space needles. The dead space in different low dead space needle and syringe combinations varied substantially. To reduce HIV transmission related to syringe sharing, needle and syringe programs need to combine this knowledge with the needs of their clients.

  4. CASAS: A Smart Home in a Box.

    Science.gov (United States)

    Cook, Diane J; Crandall, Aaron S; Thomas, Brian L; Krishnan, Narayanan C

    2013-07-01

    While the potential benefits of smart home technology are widely recognized, a lightweight design is needed for the benefits to be realized at a large scale. We introduce the CASAS "smart home in a box", a lightweight smart home design that is easy to install and provides smart home capabilities out of the box with no customization or training. We discuss types of data analysis that have been performed by the CASAS group and can be pursued in the future by using this approach to designing and implementing smart home technologies.

  5. Assessment and management of dead-wood habitat

    Science.gov (United States)

    Hagar, Joan

    2007-01-01

    The Bureau of Land Management (BLM) is in the process of revising its resource management plans for six districts in western and southern Oregon as the result of the settlement of a lawsuit brought by the American Forest Resource Council. A range of management alternatives is being considered and evaluated including at least one that will minimize reserves on O&C lands. In order to develop the bases for evaluating management alternatives, the agency needs to derive a reasonable range of objectives for key issues and resources. Dead-wood habitat for wildlife has been identified as a key resource for which decision-making tools and techniques need to be refined and clarified. Under the Northwest Forest Plan, reserves were to play an important role in providing habitat for species associated with dead wood (U.S. Department of Agriculture Forest Service and U.S. Department of the Interior Bureau of Land Management, 1994). Thus, the BLM needs to: 1) address the question of how dead wood will be provided if reserves are not included as a management strategy in the revised Resource Management Plan, and 2) be able to evaluate the effects of alternative land management approaches. Dead wood has become an increasingly important conservation issue in managed forests, as awareness of its function in providing wildlife habitat and in basic ecological processes has dramatically increased over the last several decades (Laudenslayer et al., 2002). A major concern of forest managers is providing dead wood habitat for terrestrial wildlife. Wildlife in Pacific Northwest forests have evolved with disturbances that create large amounts of dead wood; so, it is not surprising that many species are closely associated with standing (snags) or down, dead wood. In general, the occurrence or abundance of one-quarter to one-third of forest-dwelling vertebrate wildlife species, is strongly associated with availability of suitable dead-wood habitat (Bunnell et al., 1999; Rose et al., 2001). In

  6. Proceedings of the symposium on the ecology and management of dead wood in western forests

    Science.gov (United States)

    William F. Laudenslayer; Patrick J. Shea; Bradley E. Valentine; C. Phillip Weatherspoon; Thomas E. Lisle

    2002-01-01

    Dead trees, both snags (standing dead trees) and logs (downed dead trees), are critical elements of healthy and productive forests. The “Symposium on the Ecology and Management of Dead Wood in Western Forests” was convened to bring together forest researchers and managers to share the current state of knowledge relative to the values and interactions of dead wood to...

  7. Vestibular information is required for dead reckoning in the rat.

    Science.gov (United States)

    Wallace, Douglas G; Hines, Dustin J; Pellis, Sergio M; Whishaw, Ian Q

    2002-11-15

    Dead reckoning is an on-line form of spatial navigation used by an animal to identify its present location and return directly to a starting location, even after circuitous outward trips. At present, it is not known which of several self-movement cues (efferent copy from movement commands, proprioceptive information, sensory flow, or vestibular information) are used to compute homeward trajectories. To determine whether vestibular information is important for dead reckoning, the impact of chemical labyrinthectomy was evaluated in a test that demanded on-line computation of a homeward trajectory. Rats were habituated to leave a refuge that was visible from all locations on a circular table to forage for large food pellets, which they carried back to the refuge to eat. Two different probe trials were given: (1) the rats foraged from the same spatial location from a hidden refuge in the light and so were able to use visual cues to navigate; (2) the same procedure took place in the dark, constraining the animals to dead reckon. Although control rats carried food directly and rapidly back to the refuge on both probes, the rats with vestibular lesions were able to do so on the hidden refuge but not on the dark probe. The scores of vestibular reflex tests predicted the dead reckoning deficit. The vestibular animals were also impaired in learning a new piloting task. This is the first unambiguous demonstration that vestibular information is used in dead reckoning and also contributes to piloting.

  8. The Dead Sea, The Lake and Its Setting

    Science.gov (United States)

    Brink, Uri ten

    I cannot think of a subject more befitting the description of interdisciplinary research with societal relevance than the study of the Dead Sea, a terminal lake of the Jordan River in Israel and Jordan. The scientific study of the Dead Sea is intimately connected with politics, religion, archeology, economic development, tourism, and environmental change.The Dead Sea is a relatively closed geologic and limnologic system with drastic physical changes often occurring on human timescales and with a long human history to observe these changes. Research in this unique area covers diverse aspects such as active subsidence and deformation along strike-slip faults; vertical stratification and stability of the water column; physical properties of extremely saline and dense (1234 kg/m3) water; spontaneous precipitation of minerals in an oversaturated environment; origin of the unusual chemical composition of the brine; existence of life in extreme environments; use of lake level fluctuations as a paleoclimatic indicator; and effects on the environment of human intervention versus natural climatic variability. Although the Dead Sea covers a small area on a global scale, it is nevertheless one of the largest natural laboratories for these types of research on Earth. These reasons make the Dead Sea a fascinating topic for the curious mind.

  9. Accuracy in gamma spectrometry: Pileup, dead time, and fast electornics

    International Nuclear Information System (INIS)

    Lindstrom, R.M.

    1993-01-01

    An important source of inaccuracy in neutron activation analysis is the nonlinear throughput of the counting system, especially at high counting rates. Losses, due to the finite time needed for events to happen, occur in all parts of the spectrometer system: the germanium detector crystal, preamplifier, amplifier, analog-digital converter (ADC), and MCA or computer. The slowest unbuffered units are the ADC and the amplifier, followed by the crystal. Even with modern fast electronics, losses can be important, although compensating circuits can greatly improve accuracy if they are used correctly. The ADC dead time is less of a problem than it was a decade ago. For example, a modern successive-approximation ADC in the author's laboratory takes 6 μs to digitize a gamma ray in the middle of an 8192-channel spectrum, compared with 60 μs for the Wilkinson device that it replaced. Dead-time circuits in MCAs for many years have compensated very well for this dead time. Pulse pileup is as important as ADC dead time. Random coincidence, the accidental arrival of the signal from two nonrelated gamma rays at the amplifier in a time short compared to the shaping time, results in a composite pulse that distorts the spectrum. For accurate spectrometry, each such random-sum pulse should be excluded from the spectrum (pileup rejection), and the system dead time must be adjusted to compensate for the time the system is busy analyzing this rejected event (pileup live-time correction)

  10. Interaction Buckling Experiments of Box columns

    OpenAIRE

    永藤, 寿宮

    1988-01-01

    Box sections present very interesting properties in the field of compressed elements. The purpose of this experiment is to supply experimental data of interaction buckling (overall and local buckling). Test columns are classified into 4 types according to those columns length. Support conditions are pin-ended type by using new developed bowl shoe.

  11. Cereal Box Design: An Interdisciplinary Graphics Activity

    Science.gov (United States)

    Fitzgerald, Mike; Tsosie, Teri

    2012-01-01

    The cereal box design activity is intriguing both for its simplicity and the resourcefulness that it can generate in young people. Also, it lends itself to a variety of curriculums. It covers both consumerism and Design for the Environment (DfE) concepts broadly and in depth. The activity introduces a wide range of topics. They include graphic…

  12. Study of WATCH GRB error boxes

    DEFF Research Database (Denmark)

    Gorosabel, J.; Castro-Tirado, A. J.; Lund, Niels

    1995-01-01

    We have studied the first WATCH GRB Catalogue ofγ-ray Bursts in order to find correlations between WATCH GRB error boxes and a great variety of celestial objects present in 33 different catalogues. No particular class of objects has been found to be significantly correlated with the WATCH GRBs....

  13. Reflective Cracking between Precast Prestressed Box Girders

    Science.gov (United States)

    2017-06-30

    The adjacent precast prestressed concrete box-beam bridge is the bridge of choice for short and short-to-medium span bridges. This choice is because of the ease of construction, favorable span-to-depth ratios, aesthetic appeal, and high torsional sti...

  14. The Dead Sea Transform and the Dead Sea Basin - Structure and dynamics

    Science.gov (United States)

    Weber, M.; Desire Groups, D A

    2007-12-01

    DESERT and DESIRE, two multi-national, interdisciplinary research efforts by teams from Germany, Israel, Jordan and Palestine focused on the Dead Sea Transform (DST) and the Dead Sea Basin (DSB), respectively. The DST has accommodated left-lateral transform motion of 105 km between the African and Arabian plates since early Miocene (ca. 20 My), creating during this process also the prime example of a pull-apart basin, the DSB. Within DESERT the DST segment between the Dead Sea and the Red Sea called Arava/Araba Fault (AF) was studied with the following results. On plate tectonic scale the AF is a narrow, sub-vertical zone cutting through crust and lithosphere to more than 50 km depth, while the Moho depth increases smoothly from 26 km to 39 km from W to E under the DST. Several faults exist in the upper crust in a ca. 40 km wide zone around the AF, but none has kilometer-size zones of decreased seismic velocities/zones of high electrical conductivities typical for damage zones. Across the sub-vertical AF abrupt changes in lithology can be identified to a depth of 4 kilometers. The AF also acts as a barrier to fluids. The AF is the main active fault of the DST system but it has only accommodated a limited part (up to 60 km) of the overall 105 km of sinistral plate motion. Now inactive fault strands in the vicinity of the present day AF took up lateral motion until about 5 Ma ago, when the main, active fault trace shifted ca. 1 km westward to its present position. In the top few hundred meters of the AF a locally transpressional regime occurs in a 100 to 300 m wide zone of deformed and displaced material, bordered by sub-parallel faults forming positive flower structures. The damage zones of the individual faults are only 5 to 20 m wide. This narrow width is significantly smaller than at other major strike-slip faults of similar magnitude. Most of these findings are corroborated by thermo-mechanical modeling that show shear deformation in the lithosphere under the

  15. Dead Pericarps of Dry Fruits Function as Long-Term Storage for Active Hydrolytic Enzymes and Other Substances That Affect Germination and Microbial Growth

    Directory of Open Access Journals (Sweden)

    James Godwin

    2017-12-01

    Full Text Available It is commonly assumed that dead pericarps of dry indehiscent fruits have evolved to provide an additional physical layer for embryo protection and as a means for long distance dispersal. The pericarps of dry fruits undergo programmed cell death (PCD during maturation whereby most macromolecules such DNA, RNA, and proteins are thought to be degraded and their constituents remobilized to filial tissues such as embryo and endosperm. We wanted to test the hypothesis that the dead pericarp represents an elaborated layer that is capable of storing active proteins and other substances for increasing survival rate of germinating seeds. Using in gel assays we found that dead pericarps of both dehiscent and indehiscent dry fruits of various plant species including Arabidopsis thaliana and Sinapis alba release upon hydration multiple active hydrolytic enzymes that can persist in an active form for decades, including nucleases, proteases, and chitinases. Proteomic analysis of indehiscent pericarp of S. alba revealed multiple proteins released upon hydration, among them proteases and chitinases, as well as proteins involved in reactive oxygen species (ROS detoxification and cell wall modification. Pericarps appear to function also as a nutritional element-rich storage for nitrate, potassium, phosphorus, sulfur, and others. Sinapis alba dehiscent and indehiscent pericarps possess germination inhibitory substances as well as substances that promote microbial growth. Collectively, our study explored previously unknown features of the dead pericarp acting also as a reservoir of biological active proteins, and other substances capable of “engineering” the microenvironment for the benefit of the embryo.

  16. Deadly Choices empowering Indigenous Australians through social networking sites.

    Science.gov (United States)

    McPhail-Bell, Karen; Appo, Nathan; Haymes, Alana; Bond, Chelsea; Brough, Mark; Fredericks, Bronwyn

    2017-04-05

    The potential for health promotion through social networking sites (SNSs) is widely recognized. However, while health promotion prides itself in focusing on the social determinants of health, its partiality for persuading individuals to comply with health behaviours dominates the way health promotion utilizes SNSs. This paper contributes to an understanding of collaborative ways SNSs can work for health promotion agendas of self-determination and empowerment in an Indigenous Australia context. An ethnographic study was undertaken with Deadly Choices, an Indigenous-led health promotion initiative. The study involved participant observation of interactions on Deadly Choices SNSs between Deadly Choices and its online community members. Deadly Choices provides an example of SNSs providing a powerful tool to create a safe, inclusive and positive space for Indigenous people and communities to profile their healthy choices, according to Indigenous notions of health and identity. The study found five principles that underpin Deadly Choices' use of SNSs for health promotion. These are: create a dialogue; build community online and offline; incentivise healthy online engagement; celebrate Indigenous identity and culture; and prioritize partnerships. Deadly Choices SNSs empowers Indigenous people and communities to be health promoters themselves, which represents a power shift from health promotion practitioner to Indigenous people and communities and more broadly, an enactment of Indigenous self-determination on SNSs. Mainstream health promotion can learn from Indigenous health promotion practice regarding the use of SNSs for health promotion agendas. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Dynamics of TBP binding to the TATA box

    Science.gov (United States)

    Schluesche, Peter; Heiss, Gregor; Meisterernst, Michael; Lamb, Don C.

    2008-02-01

    Gene expression is highly controlled and regulated in living cells. One of the first steps in gene transcription is recognition of the promoter site by the TATA box Binding Protein (TBP). TBP recruits other transcriptions factors and eventually the RNA polymerase II to transcribe the DNA in mRNA. We developed a single pair Förster Resonance Energy Transfer (spFRET) assay to investigate the mechanism of gene regulation. Here, we apply this assay to investigate the initial binding process of TBP to the adenovirus major late (AdML) promoter site. From the spFRET measurements, we were able to identify two conformations of the TBP-DNA complex that correspond to TBP bound in the correct and the opposite orientation. Increased incubation times or the presence of the transcription factor TFIIA improved the alignment of TBP on the promoter site. Binding of TBP to the TATA box shows a rich dynamics with abrupt transitions between multiple FRET states. A frame-wise histogram analysis revealed the presence of at least six discrete states, showing that TBP binding is more complicated than previously thought. Hence, the spFRET assay is very sensitive to the conformation of the TBP-DNA complex and is very promising tool for investigating the pathway of TBP binding in detail.

  18. Tourism development challenges on the Dead Sea shore

    Directory of Open Access Journals (Sweden)

    Wendt Jan A.

    2016-12-01

    Full Text Available The Dead Sea along with Jerusalem belongs to one of the most well-known spots visited by tourists in Israel. Because of many factors, such as the water level of the Dead Sea at a depth of 430 m b.s.l. (in 2015, average salinity of 26%, hot springs and many healing salts located there, it is a unique tourist attraction on a global level. Its attractiveness is heightened by its proximity to other sites of interest, such as the Jewish fortress at Masada, Jericho, Qumran, where the Dead Sea Scrolls were found, as well as Petra, Madaba and Al-Karak on the Jordanian side of the Dead Sea. High salinity and a microclimate create perfect conditions for the development of health resorts and medical tourism. Extracting healing salts from its waters for the needs of the chemical industry is important for both the economy and medical tourism. However, as a consequence of the agricultural and urban use of the waters of the River Jordan, which flows into the Dead Sea, a persistent decrease in the lake water level has been observed over the last century. This has created a number of economic and political issues. The problems which still have to be resolved are associated with the Red Sea-Dead Sea Conduit (Canal, the division of Jordan’s water resources, conservation of the unique reservoir of the Dead Sea and the threat of hindering the development of tourism within the region. The presentation of these issues is the main aim of this research paper. The study is based on the analysis of changes in tourism flows, results of research studies and the prognosis of changes in the water level of the Dead Sea. It presents an assessment of the effects of this phenomenon on the tourist economy. At the current level of tourism flows within the region, the tourist capacity of local beaches will be exceeded in areas where the most popular tourist resorts are located. Increased expenditure on development of tourism infrastructure in the coastal zone can also be observed

  19. Simplified dead-time compensator for multiple delay SISO systems.

    Science.gov (United States)

    Torrico, Bismark Claure; Correia, Wilkley Bezerra; Nogueira, Fabrício Gonzalez

    2016-01-01

    This paper presents a dead-time compensation structure able to deal with stable and unstable multiple delay single input single output (SISO) systems. The proposed method aims to simplify the primary controller by replacing it for FIR filters placed at the feedback path. Such modification reduces the total number of parameters to be tuned which facilitates the overall design in comparison with other primary controllers normally considered. Simulation results show a better performance for the proposed control approach compared with other dead-time compensator (DTC) recently proposed in the literature. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  20. Homer and the cult of the dead in Helladic times

    Directory of Open Access Journals (Sweden)

    Odysseus Tsagarakis

    1980-12-01

    Full Text Available This paper discusses the Homeric bothros (Odyssey X 517 ff. as a possible source of information for the ritual and function of various bothroi (grave pits which are considered to be an important archaeological source. It seems that the bothroi were, by their nature, best suited to a cult of the dead and served as altars. The paper also discusses the possible reasons for the existence of the cult and argues against the view that fear of the dead motivated the cult in Helladic times.

  1. Organ donation from brain-dead and circulatory-dead donors: single-institution experiences.

    Science.gov (United States)

    Kenmochi, T; Nishiyama, S; Hayashi, M; Ito, T; Kato, Y; Hoshinaga, K

    2014-05-01

    Although the number of organ donations is extremely small in Japan, organ donation from brain dead (DBD) donors is increasing since the revised Law for Organ Transplantation was enacted on July 17, 2010. In our institution, organ donations had so far been performed from 247 donors (DCD 242, DBD 5), which is the largest number in Japan. In this study, we analyzed the status of organ donation before and after the enforcement of the revised law. After the enforcement of the revised law, the option of organ donation was shown to the more families of potential donors by the doctors or donor coordinators. However, the final number of donors was almost the same. The frequency of DBD donors of all donors increased (33.3%) as compared to 9.1% before the enforcement of the revised law. Reasons for rejection of donation from donor families were mainly based on the lack of understanding of brain death. To increase organ donation, we should promote social recognition of brain death, having the Organ Donation Card, and discussion of organ donation in each family. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. The Box Turtle: Room with a View on Species Decline.

    Science.gov (United States)

    Belzer, Bill; Steisslinger, Mary Beth

    1999-01-01

    Surveys salient aspects of eastern box-turtle natural history. Explores the societal and ecological factors that have contributed to the decline of the box-turtle population. Contains 18 references. (WRM)

  3. Extreme Dead Sea drying event during the last interglacial from the ICDP Dead Sea Deep Drill Core

    Science.gov (United States)

    Goldstein, S.; Stein, M.; Ben-Avraham, Z.; Agnon, A.; Ariztegui, D.; Brauer, A.; Haug, G.; Ito, E.; Kitagawa, H.; Torfstein, A.; Yasuda, Y.

    2012-04-01

    The ICDP funded Dead Sea Deep Drilling Project (DSDDP) recovered the longest and most complete paleo-environmental record in the Middle East, drilling holes in a deep and a shallow site extending to ~450 meters. The Dead Sea expands during the glacials and contracts during interglacials, and the sediments are an archive of the evolving climatic conditions. During glacials the sediments comprise intervals of marl (aragonite, gypsum and detritus) and during interglacials they are salts and marls. We estimate that the deep site core spans ~200 kyr (to early MIS 7). A dramatic discovery is a ~40 cm interval of rounded pebbles at ~235 m below the lake floor, the only clean pebbly unit in the entire core. It appears to be a beach layer, near the deepest part of the Dead Sea, lying above ~35 meters of mainly salt. If it is a beach layer, it implies an almost complete dry-down of the paleo-Dead Sea. The pebble layer lies within the last interglacial interval. Our initial attempt to estimate the age of the possible dry down shows an intriguing correlation between the salt-mud stratigraphy of the Dead Sea core and the oxygen isotope record of Soreq Cave, whereby excursions to light oxygen in the speleothems correspond to periods of salt deposition. Through this comparison, we estimate that the dry down occurred during MIS 5e. The occurrence of ~35 meters of mainly salt along with the pebble layer demonstrates a severe dry interval during MIS 5. This observation has implications for the Middle East today, where the Dead Sea level is dropping as all the countries in the area use the runoff. GCM models indicate a more arid future in the region. The core shows that the runoff nearly stopped during a past warm period without human intervention.

  4. Seal boxes from the Viminacium site

    Directory of Open Access Journals (Sweden)

    Milovanović Bebina

    2013-01-01

    Full Text Available Bronze seal boxes that had the function of holding the wax seal on the Viminacium site - Upper Moesia (Stari Kostolac, Serbia, mainly from the area of the necropolis (ten were found in the graves and ten at the cemetery between the graves. Six are from buildings that had a storage function, five are from public facilities - an amphitheatre, and only one find is from the military fort of the legion VII Claudia, which was stationed in Viminacium in the second half of the 1st century. Thirty-two seal boxes have been processed: nine whole, six with fragmented upper and lower parts, seven bases and ten covers. Seal boxes consist of two parts: the cover and the base. The cover is decorated with figural images, concentric rings and especially with applied ornaments. Some of the motifs are filled with enamel. The base always has three to five circular perforations at the bottom, the side walls are a height of 4 to 5 mm with two opposed notches or slots which are thought to have facilitated the tying of the seal box to a package or a document. The lock mechanism is operated using the hinges principle. Some specimens have a circular extension on the cover with a thorn on the bottom. This fits the hollow in the base, through which passes a thorn for the additional fixing of the cover. Based on shape and decoration, seal boxes were classified into five types: I - elliptical or oval shaped with a figural representation on the cover derived in relief; II/1 - leaf or heart-shaped with a special, riveted ornament; II/2 - leaf or heart-shaped with enamel on the cover; III/1 - circular showing a form in relief; III/2 - circular with cast concentric rings, with no enamel; III/3 - circular with concentric rings with enamel on the cover; IV - diamond shaped with enamel on the cover and V - square with enamel on the cover. The seal boxes dominate chronologically from the first half of the 2nd and throughout the 3rd century.

  5. Ballast system for maintaining constant pressure in a glove box

    Science.gov (United States)

    Shlichta, Paul J.

    1989-09-01

    A ballast system is disclosed for a glove box including a fixed platform on which is mounted an inflatable bag on top of which resides a cover and a weight. The variable gas volume of the inflatable bag communicates with that of the glove box via a valved tube. The weight and the gas volume are selected to maintain a relatively constant pressure in the glove box despite variations in the glove box volume while avoiding the use of complicated valving apparatus.

  6. Living with the Dead or Communicating with the dead: media practices of continuing bonds among bereaved parents

    DEFF Research Database (Denmark)

    Sandvik, Kjetil; Christensen, Dorthe Refslund

    in the shape of everyday parental activities such as playing with the child, reading bedtime stories, celebrating birthdays or just bearing the dead child in mind, the purpose of which are to keep the dead child as a present part of the parents’ and family’s continuing life. We argue that these practices...... when getting a memory tattoo. Based on observation studies and qualitative contents analysis performed since 2008 on children’s graves and on online memorial sites (Christensen & Sandvik 2013, 2014a, 2014b, 2015a) and furthermore including interviews with bereaved parents (Christensen & Sandvik...

  7. 47 CFR 90.241 - Radio call box operations.

    Science.gov (United States)

    2010-10-01

    ... box installations in areas where such frequencies are available for fixed system use subject to the... 47 Telecommunication 5 2010-10-01 2010-10-01 false Radio call box operations. 90.241 Section 90... PRIVATE LAND MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.241 Radio call box...

  8. Grey-Box Modelling of Pharmacokinetic /Pharmacodynamic Systems

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Jacobsen, Judith L.; Pedersen, Oluf

    2004-01-01

    Grey-box pharmacokinetic/pharmacodynamic (PK/PD) modelling is presented as a promising way of modelling PK/PD systems. The concept behind grey-box modelling is based on combining physiological knowledge along with information from data in the estimation of model parameters. Grey-box modelling...

  9. 30 CFR 18.49 - Connection boxes on machines.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Connection boxes on machines. 18.49 Section 18... Design Requirements § 18.49 Connection boxes on machines. Connection boxes used to facilitate replacement of cables or machine components shall be explosion-proof. Portable-cable terminals on cable reels...

  10. 31 CFR 515.326 - Custody of safe deposit boxes.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Custody of safe deposit boxes. 515... Definitions § 515.326 Custody of safe deposit boxes. Safe deposit boxes shall be deemed to be in the custody... upon the meaning of the term custody. ...

  11. 31 CFR 500.326 - Custody of safe deposit boxes.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Custody of safe deposit boxes. 500... Definitions § 500.326 Custody of safe deposit boxes. Safe deposit boxes shall be deemed to be in the custody... upon the meaning of the term custody. ...

  12. 49 CFR 230.103 - Tender roller bearing journal boxes.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Tender roller bearing journal boxes. 230.103... Locomotives and Tenders Running Gear § 230.103 Tender roller bearing journal boxes. Tender roller bearing journal boxes shall be maintained in a safe and suitable condition. ...

  13. 49 CFR 230.102 - Tender plain bearing journal boxes.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Tender plain bearing journal boxes. 230.102... Locomotives and Tenders Running Gear § 230.102 Tender plain bearing journal boxes. Plain bearing journal boxes... expected to damage the bearing; or have a detrimental effect on the lubrication of the journal and bearing...

  14. Using Origami Boxes to Explore Concepts of Geometry and Calculus

    Science.gov (United States)

    Wares, Arsalan

    2011-01-01

    The purpose of this classroom note is to provide an example of how a simple origami box can be used to explore important concepts of geometry and calculus. This article describes how an origami box can be folded, then it goes on to describe how its volume and surface area can be calculated. Finally, it describes how the box could be folded to…

  15. 77 FR 74513 - Folding Gift Boxes From China

    Science.gov (United States)

    2012-12-14

    ... COMMISSION Folding Gift Boxes From China Determination On the basis of the record \\1\\ developed in the... antidumping duty order on folding gift boxes from China would be likely to lead to continuation or recurrence... Commission are contained in USITC Publication 4365 (November 2012), entitled Folding Gift Boxes from China...

  16. SMRT has tissue-specific isoform profiles that include a form containing one CoRNR box

    International Nuclear Information System (INIS)

    Short, Stephen; Malartre, Marianne; Sharpe, Colin

    2005-01-01

    SMRT acts as a corepressor for a range of transcription factors. The amino-terminal part of the protein includes domains that mainly mediate transcriptional repression whilst the carboxy-terminal part includes domains that interact with nuclear receptors using up to three motifs called CoRNR boxes. The region of the SMRT primary transcript encoding the interaction domains is subject to alternative splicing that varies the inclusion of the third CoRNR box. The profile in mice includes an abundant, novel SMRT isoform that possesses just one CoRNR box. Mouse tissues therefore express SMRT isoforms containing one, two or three CoRNR boxes. In frogs, the SMRT isoform profile is tissue-specific. The mouse also shows distinct profiles generated by differential expression levels of the SMRT transcript isoforms. The formation of multiple SMRT isoforms and their tissue-specific regulation indicates a mechanism, whereby cells can define the repertoire of transcription factors regulated by SMRT

  17. Dimethyloxalylglycine treatment of brain-dead donor rats improves both donor and graft left ventricular function after heart transplantation.

    Science.gov (United States)

    Hegedűs, Péter; Li, Shiliang; Korkmaz-Icöz, Sevil; Radovits, Tamás; Mayer, Tobias; Al Said, Samer; Brlecic, Paige; Karck, Matthias; Merkely, Béla; Szabó, Gábor

    2016-01-01

    Hypoxia inducible factor (HIF)-1 pathway signalling has a protective effect against ischemia/reperfusion injury. The prolyl-hydroxylase inhibitor dimethyloxalylglycine (DMOG) activates the HIF-1 pathway by stabilizing HIF-1α. In a rat model of brain death (BD)-associated donor heart dysfunction we tested the hypothesis that pre-treatment of brain-dead donors with DMOG would result in a better graft heart condition. BD was induced in anesthetized Lewis rats by inflating a subdurally placed balloon catheter. Controls underwent sham operations. Then, rats were injected with an intravenous dose of DMOG (30 mg/kg) or an equal volume of physiologic saline. After 5 hours of BD or sham operation, hearts were perfused with a cold (4°C) preservation solution (Custodiol; Dr. Franz Köhler Chemie GmbH; Germany), explanted, stored at 4°C in Custodiol, and heterotopically transplanted. Graft function was evaluated 1.5 hours after transplantation. Compared with control, BD was associated with decreased left ventricular systolic and diastolic function. DMOG treatment after BD improved contractility (end-systolic pressure volume relationship E'max: 3.7 ± 0.6 vs 3.1 ± 0.5 mm Hg/µ1; p brain-dead group. After heart transplantation, DMOG treatment of brain-dead donors significantly improved the altered systolic function and decreased inflammatory infiltration, cardiomyocyte necrosis, and DNA strand breakage. In addition, compared with the brain-dead group, DMOG treatment moderated the pro-apoptotic changes in the gene and protein expression. In a rat model of potential brain-dead heart donors, pre-treatment with DMOG resulted in improved early recovery of graft function after transplantation. These results support the hypothesis that activation of the HIF-1 pathway has a protective role against BD-associated cardiac dysfunction. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  18. Dead Zones in LX-17 and PBX 9502

    Energy Technology Data Exchange (ETDEWEB)

    Souers, P C; Andreski, H G; Batteux, J; Bratton, B; Cabacungan, C; Cook, III, C F; Fletcher, S; Garza, R; Grimsley, D; Handly, J; Hernandez, A; McMaster, P; Molitoris, J D; Palmer, R; Prindiville, J; Rodriguez, J; Schneberk, D; Wong, B; Vitello, P

    2005-09-06

    Pin and X-ray corner-turning data have been taken on ambient LX-17 and PBX 9052, and the results are listed in tables as an aid to future modeling. The results have been modeled at 4 zones/mm with a reactive flow approach that varies the burn rate as a function of pressure. A single rate format is used to simulate failure and detonation in different pressure regimes. A pressure cut-off must also be reached to initiate the burn. Corner-turning and failure are modeled using an intermediate pressure rate region, and detonation occurs at high pressure. The TATB booster is also modeled using reactive flow, and X-ray tomography is used to partition the ram-pressed hemisphere into five different density regions. The model reasonably fits the bare corner-turning experiment but predicts a smaller dead zone with steel confinement, in contradiction with experiment. The same model also calculates the confined and unconfined cylinder detonation velocities and predicts the failure of the unconfined cylinder at 3.75 mm radius. The PBX 9502 shows a smaller dead zone than LX-17. An old experiment that showed a large apparent dead zone in Comp B was repeated with X-ray transmission and no dead zone was seen. This confirms the idea that a variable burn rate is the key to modeling. The model also produces initiation delays, which are shorter than those found in time-to-detonation.

  19. "The Northern Lights" Investigative Reporting Covers Deadly Decisions.

    Science.gov (United States)

    Srour, George

    2001-01-01

    Presents a story package from the high school newspaper "The Northern Lights," called "Deadly Decisions." Includes an editorial, an eyewitness account, a timeline of the coverage itself, an interview with a local TV reporter, photographs, and a graph of the events the stories covered. (SR)

  20. Eating the dead in Madagascar | Campbell | South African Medical ...

    African Journals Online (AJOL)

    They may be supported in societies under stress or in times of famine, to reflect aggression and antisocial behaviour (in cases where the bodies of enemies killed in battle or people who have harmed the family are eaten), or to honour a dead kinsman. It was, for example, noted in Madagascar during the imperial campaigns ...

  1. [Forensic Analysis of 20 Dead Cases Related to Heroin Abuse].

    Science.gov (United States)

    Huang, W Q; Li, L H; Li, Z; Hong, S J

    2016-08-01

    To perform retrospective analysis on 20 dead cases related to heroin abuse, and to provide references for the forensic assessment of correlative cases. Among 20 dead cases related to heroin abuse, general situation, using method of drug, cause of death and result of forensic examination were analyzed by statistical analysis for summarizing the cause of death and pathologic changes. The dead were mostly young adults, with more male than female. The results of histopathological examinations showed non-specific pathological changes. There were four leading causes of death, including acute poisoning of heroin abuse or leakage (13 cases, 65%), concurrent diseases caused by heroin abuse (3 cases, 15%), inspiratory asphyxia caused by taking heroin (2 cases, 10%), and heroin withdrawal syndrome (2 cases, 10%). The forensic identification on dead related to heroin abuse must base on the comprehensive autopsy, and combine with the qualitative and quantitative analysis of heroin and its metabolites in death and the case information, as well as the scene investigation. Copyright© by the Editorial Department of Journal of Forensic Medicine

  2. Dead Metaphor in Selected Advertisements in Nigerian Dailies ...

    African Journals Online (AJOL)

    Dead metaphors and images are often enlivened and empowered by advertisers to help their commUlzication and to achieve bewitching effects. It is interesting to see words and phrases that may be presumed to have been drained of their linguistic strength being brought back to currency and made to act fast in aiding ...

  3. Theory of precipitation effects on dead cylindrical fuels

    Science.gov (United States)

    Michael A. Fosberg

    1972-01-01

    Numerical and analytical solutions of the Fickian diffusion equation were used to determine the effects of precipitation on dead cylindrical forest fuels. The analytical solution provided a physical framework. The numerical solutions were then used to refine the analytical solution through a similarity argument. The theoretical solutions predicted realistic rates of...

  4. Dead Reckoning Localization Technique for Mobile Wireless Sensor Networks

    OpenAIRE

    Rashid, Haroon; Turuk, Ashok Kumar

    2015-01-01

    Full paper at: http://arxiv.org/pdf/1504.06797.pdfThis paper shows how a mobile node can be localized with less than three beacon nodes. It uses a technique known as dead-reckoning for localization of nodes at specific intervals

  5. Stylistic Variation In Three English Translations Of The Dead Sea ...

    African Journals Online (AJOL)

    Since the discovery of the Dead Sea Scrolls in 1947 different English translations were published. In this article the stylistic variation of three of these translations are analysed. It is suggested that the issue of stylistic variation boils down to linguistically inscribed preference in the choice and construction of discourses in the ...

  6. Piecing Together the Past: The Dead Sea Schools.

    Science.gov (United States)

    Ulrich, Eugene; And Others

    1995-01-01

    Illustrates the astonishing coordination of archaeological and scholarly activities surrounding the Dead Sea Scrolls. First discovered by Bedouin nomads in 1947, the Scrolls consist of a few complete manuscripts and over 80,000 fragments. Discusses the early Christian sect that produced the Scrolls, and provides current perspectives on the…

  7. Literary Genres in Poetic Texts from the Dead Sea Scrolls

    Science.gov (United States)

    Pickut, William Douglas

    2017-01-01

    Among the texts of the Dead Sea Scrolls, there are four literary compositions that bear the superscriptional designations shir and mizmor. These designations correspond directly to superscriptional designations provided many times in both the now-canonical Psalter and the various witnesses to those texts unearthed at Qumran. On its face, this fact…

  8. Comparison of burning characteristics of live and dead chaparral fuels

    Science.gov (United States)

    L. Sun; X. Zhou; S. Mahalingam; D.R. Weise

    2006-01-01

    Wildfire spread in living vegetation, such as chaparral in southern California, often causes significant damage to infrastructure and ecosystems. The effects of physical characteristics of fuels and fuel beds on live fuel burning and whether live fuels differ fundamentally from dead woody fuels in their burning characteristics are not well understood. Toward this end,...

  9. Brought in Dead: An Avoidable Delay in Maternal Deaths.

    Science.gov (United States)

    Kumar, Aruna; Agrawal, Neha

    2016-10-01

    Maternal brought in dead are the patient who dies in the need of adequate medical care. These deaths are often not analyzed sincerely as they are not institutional deaths. Our aim is to find out actual life threatening cause of delay leading to death. Patients brought dead to casualty were seen by the doctors on duty in Department of Obstetrics and Gynaecology,Gandhi Medical College, Bhopal round the clock. Cause of death was analyzed by verbal autopsy of attendants and referral letter from the institute. In this analytical study a complete evaluation of brought deaths from January 2011 to Decmeber 2014 was done. A total of 64 brought in deaths were reported in this 4 year duration. Most common cause of death was postpartum hemorrhage (54.68 %) followed by hypertension (15.62 %) and the most common cause of delay was delay in getting adequate treatment (56.25 %). The brought in dead are the indicator of the three delays in getting health care. Challenges appear to be enormous to be tackled. Timely management proves to be critical in preventing maternal death. Thus it appears that community education about pregnancy and its complications, EmOC training at FRU and strict adherence to referral protocol may help us to reduce the brought dead burden.

  10. Gastric necrosis four years after fundoplication causing a dead foetus

    DEFF Research Database (Denmark)

    Thinggaard, Ebbe; Skovsen, Anders Peter; Kildsig, Jeppe

    2014-01-01

    A 31-year-old pregnant woman was admitted and treated for diabetic ketoacidosis. As the patient deteriorated and the viability of the foetus was uncertain a CT scan was done which showed free fluid and air intraabdominally. Surgery was performed. A dead foetus was delivered and a 2 × 5 cm necrotic...

  11. Dead wood in European beech (Fagus sylvatica) forest reserves

    NARCIS (Netherlands)

    Christensen, M.; Hahn, K.; Mountford, E.P.; Ódor, P.; Standovár, T.; Rozenbergar, D.; Diaci, J.; Wijdeven, S.M.J.; Meyer, P.; Winter, S.; Vrska, T.

    2005-01-01

    Data were analysed on the volume of dead wood in 86 beech forest reserves, covering most of the range of European beech forests. The mean volume was 130 m3/ha and the variation among reserves was high, ranging from almost nil to 550 m3/ha. The volume depended significantly on forest type, age since

  12. Bipolar disorder, childhood bereavement, and the return of the dead ...

    African Journals Online (AJOL)

    Upon its head, with red extended mouth and solitary eye of fire, sat the hideous beast whose craft had seduced me into murder ...' From 'The Black Cat', written c. age 35 (Poe 1975:230). Keywords: Edgar Allan Poe; bipolar disorder, childhood bereavement, and the return of the dead; literary criticism; American poetry; ...

  13. Hypoalbuminaemia in brain-dead donors for liver transplantation

    African Journals Online (AJOL)

    Nicky

    Liver transplantation has become established as the treat- ment of choice for most patients with end-stage liver disease and is performed on a routine basis in most major centres throughout the world. The majority of donors for liver trans- plantation are brain-dead cadaver donors following either a severe head injury or a ...

  14. Remembering Important People On The Day Of The Dead

    Science.gov (United States)

    Curriculum Review, 2005

    2005-01-01

    This article describes a project that can help students learn more about historic figures-or remember lost loved ones--with this Day of the Dead project from Frida Kahlo and Diego Rivera. The purpose is to remember the wonderful things the person did, and to celebrate his or her life. Directions for construction, as well as a suggested list of…

  15. The prevalence and challenges of abandoned dead neonates in an ...

    African Journals Online (AJOL)

    %) cases, as depicted in Table 1. The parents/caregivers of 618 (56.5%) dead babies were illiterate and of a low socioeconomic class. Financial constraint experienced by the parents/caregivers of 309. (28.3%) babies, repulsion toward obvious ...

  16. Preparedness of Response to Deadly Outbreaks: Lessons Learnt ...

    African Journals Online (AJOL)

    Some of the lessons learnt included improved work efficiency, built staff resilience to work long hours under stressful conditions and consciously managing aseptic techniques. Conclusion: Exposure to some adverse conditions such as managing work operations in the midst of a deadly outbreak such as Ebola may have a ...

  17. Antimicrobial properties of Dead Sea black mineral mud.

    Science.gov (United States)

    Ma'or, Zeev; Henis, Yigal; Alon, Yaacov; Orlov, Elina; Sørensen, Ketil B; Oren, Aharon

    2006-05-01

    The unique, black, hypersaline mud mined from the Dead Sea shores is extensively used in mud packs, masks, and topical body and facial treatments in spas surrounding the lake, and in cosmetic preparations marketed worldwide, but little is known about its antimicrobiological properties. We performed detailed microbial and chemical analysis of Dead Sea mineral mud compounded in dermatological and cosmetic preparations. Using conventional bacteriological media (with or without salt augmentation), we found surprisingly low numbers of colony-forming microorganisms in the mud. The highest counts (up to 20,000 colonies per gram, mostly consisting of endospore-forming bacteria) were obtained on sheep blood agar. Test microorganisms (i.e. Escherichia coli, Staphylococcus aureus, Propionibacterium acnes, Candida albicans) rapidly lost their viability when added to the mud. Zones of growth inhibition were observed around discs of Dead Sea mud placed on agar plates inoculated with Candida or with Propionibacterium, but not with Staphylococcus or Escherichia. The effect was also found when the mud was sterilized by gamma irradiation. Using (35)S-labeled sulfate as a tracer, bacterial dissimilatory sulfate reduction could be demonstrated at a low rate (0.13 +/- 0.03 nmol/cm(3).d). The antibacterial properties of Dead Sea mud are probably owing to chemical and/or physical phenomena. Possible modes of antimicrobial action of the mud in relation to its therapeutic properties are discussed.

  18. Necrotizing fasciitis: A deadly disease | Cree | East and Central ...

    African Journals Online (AJOL)

    Background: Knowledge of the diagnosis, cause, course and required treatment of this deadly disease among physicians and surgeons around the world is limited. Methods: A study was undertaken at University Teaching Hospital (UTH), Lusaka Zambia to review the incidence, associated pathology, management given, ...

  19. Book Review Lifeblood: How to Change the World, One Dead ...

    African Journals Online (AJOL)

    Book Review Lifeblood: How to Change the World, One Dead Mosquito at a Time By Alex Perry (2011). Melissa Raemaekers. Abstract. Pp xiv + 219. R210. Picador Africa, Pan Macmillan, South Africa. 2011. ISBN 978-1-77010-146-3. February 2012, Vol. 102, No. 2 SAMJ. Full Text: EMAIL FREE FULL TEXT EMAIL FREE ...

  20. Assessment of biofuel potential of dead neem leaves ( Azadirachta ...

    African Journals Online (AJOL)

    Dead leaves of neem trees in the Sahelian urban zone are among the wastes that are underutilized, since it is either buried or burnt, and thus, contribute to increased environmental pollution. Unfortunately, the lack of information on the biomass and energy potentials of these wastes empedes any initiative for its industrial ...

  1. Cowboys and zombies: destabilizing patriarchal discourse in The Walking Dead

    NARCIS (Netherlands)

    Hassler-Forest, D.

    2012-01-01

    The serialized comic book The Walking Dead, written by Robert Kirkman and drawn by Charlie Adlard, has been published by Image Comics from October 2003, and is still being released in monthly instalments as of this writing. It has won numerous awards, including the prestigious Eisner Award for Best

  2. A white box perspective on behavioural adaptation

    DEFF Research Database (Denmark)

    Bruni, Roberto; Corradini, Andrea; Gadducci, Fabio

    2015-01-01

    We present a white-box conceptual framework for adaptation developed in the context of the EU Project ASCENS coordinated by Martin Wirsing. We called it CoDA, for Control Data Adaptation, since it is based on the notion of control data. CoDA promotes a neat separation between application and adap......We present a white-box conceptual framework for adaptation developed in the context of the EU Project ASCENS coordinated by Martin Wirsing. We called it CoDA, for Control Data Adaptation, since it is based on the notion of control data. CoDA promotes a neat separation between application...... and adaptation logic through a clear identification of the set of data that is relevant for the latter. The framework provides an original perspective from which we survey a representative set of approaches to adaptation, ranging from programming languages and paradigms to computational models and architectural...

  3. The Central Nervous System of Box Jellyfish

    DEFF Research Database (Denmark)

    Garm, Anders Lydik; Ekström, Peter

    2008-01-01

    of behaviors in the box jellyfish such as obstacle avoidance and navigation. The need to process the visual information and turn it into the appropriate behavior puts strong demands on the nervous system of box jellyfish, which appears more elaborate than in other cnidarians. Here, the central part...... of this nervous system is described. Each rhopalium holds a separate part of the CNS with 1,000 nerve cells and a large amount of neuropil. The rhopalial nervous system has several subsystems defined by the anatomy, location, and immunocytochemistry of the cells. Most of the subsystems connect to one or more...... of the eye types, and it is likely that the rhopalial nervous system accounts for most of the visual processing. The major part of the CNS is made up of a ring nerve encircling the bell shaped body. The ring nerve holds around 10,000 cells and is directly connected to all four rhopalial nervous systems...

  4. Fatal exit the automotive black box debate

    CERN Document Server

    Kowalick, Tom

    2005-01-01

    "Fatal Exit: The Automotive Black Box Debate cuts through thirty years of political wrangling and institutional biases to provide an argument for the Motor Vehicle Event Data Recorder (MVEDR). This automotive equivalent of an airplane's flight recorder or black box is intended to solve the mysteries of car crashes and improve the safety of our roads. The reader is taken inside the automotive industry and the government highway safety establishment to foster an understanding of the politics and the positions on all sides of this safety debate. The author takes an unbiased approach, chronologically presenting each argument and uncovering the agendas and mandates of each of the stakeholders." "This publication is essential reading for all consumers who need to have their voices heard on this critical issue, as well as for attorneys, public safety advocates, public policy administrators, engineers, automotive professionals, journalists, and insurance executives."--Jacket.

  5. Monitoring Instrument for X-Ray Box

    CERN Document Server

    Cifuentes Ospina, Alberto; Kuehn, Susanne; Schaepe, Steffen; CERN. Geneva. EP Department

    2017-01-01

    A humidity and temperature readout instrument has been designed and implemented in order to monitor the X-Ray Box used for testing the silicon detectors prototypes of the ITk. The sensors are connected to an Arduino Mega board equipped with 16 analog inputs and a serial port to a computer. A user-friendly software has been also designed in order to give an easy access to all measurements.

  6. Removable glove for a glove box

    International Nuclear Information System (INIS)

    Lucas, J.M.

    1982-01-01

    The glove includes one part forming a cuff and another part forming the glove. These two parts are joined in a leak-tight manner by a rigid ring. The glove part is interchangeable without breaking the seal through two neighbouring grooves formed on the ring to receive a bead made on the open end of the glove. The grooves are visible when the glove is placed outside the glove box, thereby enabling the glove part to be changed in this position [fr

  7. The future of grey-box fuzzing

    OpenAIRE

    Hjelt, Isak

    2017-01-01

    Society are becoming more dependent on software, and more artifacts are being connected to the Internet each day [31]. This makes the work of tracking down vulnerabilities in software a moral obligation for software developers. Since manual testing is expensive [7], automated bug finding techniques are attractive within the quality assurance field, since it can save companies a lot of money. This thesis summarizes the research of an automated bug finding technique called grey-box fuzzing, wit...

  8. PCB-Based Break-Out Box

    Science.gov (United States)

    Lee, Jason H.

    2011-01-01

    Break-out boxes (BOBs) are necessary for all electrical integration/cable checkouts and troubleshooting. Because the price of a BOB is high, and no work can be done without one, often the procedure stops, simply waiting for a BOB. A less expensive BOB would take less time in the integration, testing, and troubleshooting process. The PCB-based BOB works and looks the same as a standard JPL BOB, called Gold Boxes. The only differences between the old BOB and the new PCB-based BOB is that the new one has 80 percent of its circuitry in a printed circuit board. This process reduces the time for fabrication, thus making the BOBs less expensive. Moreover, because of its unique design, the new BOBs can be easily assembled and fixed. About 80 percent of the new PCB-based BOB is in a $22 (at the time of this reporting) custom-designed, yet commercially available PCB. This device has been used successfully to verify that BOB cables were properly made. Also, upon completion, the BOB was beeped out via a multimeter to ensure that all sockets on the connectors were properly connected to the respective banana jack. When compared to the Gold Box BOBs, the new BOB has many advantages. It is much more cost efficient, it delivers equal usability at substantially lower cost of the BOB, and the Gold Box is much heavier when compared to the new BOB. The new BOB is also a bit longer and much more versatile in that connectors are easily changeable and if a banana jack is broken, it can be replaced instead of throwing away an entire BOB.

  9. Dry boxes and inert atmosphere techniques

    International Nuclear Information System (INIS)

    Bartak, D.E.

    1987-01-01

    Practitioners need to conduct experiments with molten salts in an inert atmosphere owing to the chemical reactivity of these media. Most fused salt solvent systems show reactivity to water and/or oxygen, which results in significant chemical changes in the properties of these solvents. Although several studies on the nature of an oxygen/oxide electrode in this melt have been reported, the reactions have not been fully understood because of apparent water contamination in many cases. Nitrate melt systems are also hygroscopic; for example, the LiNO 3 -KNO 3 eutectic (177 0 C) absorbs water to at least 0.2% by weight. The result is that the electrochemistry of heavier, electropositive metal ions has been significantly altered. In addition, trace amounts of water have been shown to significantly affect the oxygen-oxide redox chemistry in NaNO 3 -KNO 3 melts (250 0 C). The haloaluminates, which include AlCl 3 -NaCl (175 0 C), as well as AlCl 3 -organic salt binaries are particularly sensitive to the presence of both oxygen and moisture. Oxygen is a strong oxidant in the fused hydroxide systems with formation of superoxide ion from either oxide or water. This chapter describes general, inert atmosphere techniques which can be used by the molten salt experimentalist. Because of the limitations of volatility, vacuum manipulations are not considered. Rather, the use of glove boxes, glove bags, and inert bench-top techniques are discussed. The areas covered are: glove box and bag equipment, operation and maintenance of glove boxes and glove bags, and common operations conducted inside glove boxes

  10. Uveal melanoma: relatively rare but deadly cancer

    Science.gov (United States)

    Kaliki, S; Shields, C L

    2017-01-01

    Although it is a relatively rare disease, primarily found in the Caucasian population, uveal melanoma is the most common primary intraocular tumor in adults with a mean age-adjusted incidence of 5.1 cases per million per year. Tumors are located either in iris (4%), ciliary body (6%), or choroid (90%). The host susceptibility factors for uveal melanoma include fair skin, light eye color, inability to tan, ocular or oculodermal melanocytosis, cutaneous or iris or choroidal nevus, and BRCA1-associated protein 1 mutation. Currently, the most widely used first-line treatment options for this malignancy are resection, radiation therapy, and enucleation. There are two main types of radiation therapy: plaque brachytherapy (iodine-125, ruthenium-106, or palladium-103, or cobalt-60) and teletherapy (proton beam, helium ion, or stereotactic radiosurgery using cyber knife, gamma knife, or linear accelerator). The alternative to radiation is enucleation. Although these therapies achieve satisfactory local disease control, long-term survival rate for patients with uveal melanoma remains guarded, with risk for liver metastasis. There have been advances in early diagnosis over the past few years, and with the hope survival rates could improve as smaller tumors are treated. As in many other cancer indications, both early detection and early treatment could be critical for a positive long-term survival outcome in uveal melanoma. These observations call attention to an unmet medical need for the early treatment of small melanocytic lesions or small melanomas in the eye to achieve local disease control and vision preservation with the possibility to prevent metastases and improve overall patient survival. PMID:27911450

  11. Effectiveness of box trainers in laparoscopic training

    Directory of Open Access Journals (Sweden)

    Dhariwal Anender

    2007-01-01

    Full Text Available Rationale and Objectives: Various devices are used to aid in the education of laparoscopic skills ranging from simple box trainers to sophisticated virtual reality trainers. Virtual reality system is an advanced and effective training method, however it is yet to be adopted in India due to its cost and the advanced technology required for it. Therefore, box trainers are being used to train laparoscopic skills. Hence this study was undertaken to assess the overall effectiveness of the box-training course. Study Procedure: The study was conducted during six-day laparoscopic skills training workshops held during 2006. Twenty five surgeons; age range of 26 to 45 years, of either sex, who had not performed laparoscopic surgery before; attending the workshop were evaluated. Each participant was given a list of tasks to perform before beginning the box-training course on day one and was evaluated quantitatively by rating the successful completion of each test. Evaluation began when the subject placed the first tool into the cannula and ended with task completion. Two evaluation methods used to score the subject, including a global rating scale and a task-specific checklist. After the subject completed all sessions of the workshop, they were asked to perform the same tasks and were evaluated in the same manner. For each task completed by the subjects, the difference in the scores between the second and first runs were calculated and interpreted as an improvement as a percentage of the initial score. Statistical Analysis: Wilcoxon matched-paired signed-ranks test was applied to find out the statistical significance of the results obtained. Results: The mean percentage improvement in scores for both the tasks, using global rating scale, was 44.5% + 6.930 (Mean + SD. For task 1, using the global rating scale mean percentage improvement was 49.4% + 7.948 (Mean + SD. For task 2, mean percentage improvement using global rating scale was 39.6% + 10.4 (Mean

  12. Extreme drying event in the Dead Sea basin during MIS5 from the ICDP Dead Sea Deep Drill Core

    Science.gov (United States)

    Goldstein, S. L.; Stein, M.; Ben-Avraham, Z.; Agnon, A.; Ariztegui, D.; Brauer, A.; Haug, G. H.; Ito, E.; Kitagawa, H.; Torfstein, A.; Yasuda, Y.; The Icdp-Dsddp Scientific Party

    2011-12-01

    The ICDP funded Dead Sea Deep Drilling Project (DSDDP) recovered the longest and most complete paleo-environmental record in the Middle East, drilling holes of ~450 and ~350 meters in length in deep (~300 m below the lake level) and shallow sites (~3 mbll) respectively. The Dead Sea expands during the glacials and contracts during interglacials, and the sediments comprise a geological archive of the evolving environmental conditions (e.g. rains, floods, dust-storms, droughts). Dead Sea sediments include inorganic aragonite, allowing for dating by U-series (e.g. Haase-Schramm et al. GCA 2004). The deep site cores were opened and described in June 2011. The cores are composed mainly of alternating intervals of marl (aragonite, gypsum and detritus) during glacials, and salts and marls during interglacials. From this stratigraphy we estimate that the deep site core spans ~200 kyr (to the boundary of MIS 6 and 7). A dramatic discovery is a ~40 cm thick interval of partly rounded pebbles at ~235 m below the lake floor. This is the only clean pebbly unit in the entire core. It appears to be a beach layer, near the deepest part of the Dead Sea, lying above ~35 meters of mainly salt. If it is a beach layer, it implies an almost complete dry-down of the paleo-Dead Sea. The pebble layer lies within the last interglacial interval. Our initial attempt to more precisely estimate the age of the possible dry down shows an intriguing correlation between the salt-mud stratigraphy of the Dead Sea core and the oxygen isotope record of Soreq Cave, whereby excursions to light oxygen in the speleothems correspond to periods of salt deposition. Through this comparison, we estimate that the possible dry down occurred during MIS 5e. The occurrence of ~35 meters of mainly salt along with the pebble layer demonstrates a severe dry interval during MIS 5. This observation has implications for the Middle East today, where the Dead Sea level is dropping as all the countries in the area use the

  13. Prohibiting Headgear for Safety in Amateur Boxing? Opinion of the Canadian Boxing Community: an Online Poll.

    Science.gov (United States)

    Dickinson, Philip; Rempel, Philip

    In 2013, the Amateur International Boxing Association (AIBA) introduced a rule banning headgear for male-senior open class boxers during competition. The AIBA has defended the rule change as motivated by safety and supported by internal unpublished studies. As a result, in 2018, the AIBA plans to universally prohibit headgear in competition: for all competitors (male and female), all ages and all levels. Within Canada, this ruling has generated controversy in the boxing community, yet there has been no overall measure of opinion. To address this, we instituted a voluntary, anonymous, online open-access poll to allow members of the boxing community to express their stance on headgear use in competition. In total, 636 responses were received. A total of 71.5 % of Canadian respondents believed headgear should be mandatory at all levels. Only 5.8 % agreed that headgear should be prohibited, as planned for 2018. Estimating results on a representative breakdown of boxing membership in Canada, a similar pattern emerged, whereby 68.2 % concurred with mandatory headgear while only 4.95 % supported its prohibition. Parents of boxers were almost unanimously against banning headgear, stating they would change sports as a result. Similarly, only 1.7 % of women believed headgear should be prohibited. The consensus of the Canadian boxing community largely opposes the rule changes that the AIBA has implemented. The results highlight risks posed to the long-term viability of the sport, if significant grassroots safety concerns are disregarded.

  14. 76 FR 63341 - Culturally Significant Objects Imported for Exhibition Determinations: “The Dead Sea Scrolls...

    Science.gov (United States)

    2011-10-12

    ... for Exhibition Determinations: ``The Dead Sea Scrolls: Life and Faith in Biblical Times'' SUMMARY... objects to be included in the exhibition ``The Dead Sea Scrolls: Life and Faith in Biblical Times...

  15. Analysis of archaeal communities in Gulf of Mexico dead zone sediments.

    Science.gov (United States)

    Sediments may contribute significantly to Louisiana continental shelf “dead zone” hypoxia but limited information hinders comparison of sediment biogeochemistry between norm-oxic and hypoxic seasons. Dead zone sediment cores collected during hypoxia (September 2006) had higher l...

  16. Smoking Out a Deadly Threat: Tobacco Use in the LGBT Community

    Science.gov (United States)

    ... Out a Deadly Threat: Tobacco Use in the LGBT Community Disparities in Lung Health Series "Smoking Out a Deadly Threat: Tobacco Use in the LGBT Community" is part of the American Lung Association's ...

  17. Occurrence of organohalogens at the Dead Sea Basin

    Science.gov (United States)

    Tubbesing, Christoph; Kotte, Karsten; Keppler, Frank; Krause, Torsten; Bahlmann, Enno; Schöler, Heinfried

    2013-04-01

    Most arid and semi-arid regions are characterized by evaporites, which are assured sources for volatile organohalogens (VOX) [1]. These compounds play an important role in tropospheric and stratospheric chemistry. The Dead Sea between Israel and Jordan is the world's most famous and biggest all-season water covered salt lake. In both countries chemical plants like the Dead Sea Works and the Arab Potash Company are located at the southern part of the Dead Sea and mine various elements such as bromine and magnesium. Conveying sea water through constructed evaporation pans multifarious salts are enriched and precipitated. In contrast, the Northern basin and main part of the Dead Sea has remained almost untouched by industrial salt production. Its fresh water supply from the Jordan River is constantly decreasing, leading to further increased salinity. During a HALOPROC campaign (Natural Halogenation Processes in the Environment) we collected various samples including air, soils, sediments, halophytic plants, ground- and seawater from the Northern and Southern basin of the Israeli side of the Dead Sea. These samples were investigated for the occurrence of halocarbons using different analytical techniques. Most samples were analyzed for volatile organohalogens such as haloalkanes using gas chromatography- mass spectrometry (GC-MS). Interestingly, there is a strong enrichment of trihalomethanes (THM), especially all chlorinated and brominated ones and also the iodinated compound dichloroiodomethane were found in the Southern basin. In addition, volatile organic carbons (VOC) such as ethene and some other alkenes were analyzed by a gas chromatography-flame ionisation detector (GC-FID) to obtain further information about potential precursors of halogenated compounds. Halophytic plants were investigated for their potential to release chloromethane and bromomethane but also for their stable carbon and hydrogen isotope composition. For this purpose, a plant chamber was

  18. Complete mitochondrial genome of Cuora trifasciata (Chinese three-striped box turtle), and a comparative analysis with other box turtles.

    Science.gov (United States)

    Li, Wei; Zhang, Xin-Cheng; Zhao, Jian; Shi, Yan; Zhu, Xin-Ping

    2015-01-25

    Cuora trifasciata has become one of the most critically endangered species in the world. The complete mitochondrial genome of C. trifasciata (Chinese three-striped box turtle) was determined in this study. Its mitochondrial genome is a 16,575-bp-long circular molecule that consists of 37 genes that are typically found in other vertebrates. And the basic characteristics of the C. trifasciata mitochondrial genome were also determined. Moreover, a comparison of C. trifasciata with Cuora cyclornata, Cuora pani and Cuora aurocapitata indicated that the four mitogenomics differed in length, codons, overlaps, 13 protein-coding genes (PCGs), ND3, rRNA genes, control region, and other aspects. Phylogenetic analysis with Bayesian inference and maximum likelihood based on 12 protein-coding genes of the genus Cuora indicated the phylogenetic position of C. trifasciata within Cuora. The phylogenetic analysis also showed that C. trifasciata from Vietnam and China formed separate monophyletic clades with different Cuora species. The results of nucleotide base compositions, protein-coding genes and phylogenetic analysis showed that C. trifasciata from these two countries may represent different Cuora species. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. 49 CFR 178.512 - Standards for steel or aluminum boxes.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Standards for steel or aluminum boxes. 178.512... aluminum boxes. (a) The following are identification codes for steel or aluminum boxes: (1) 4A for a steel box; and (2) 4B for an aluminum box. (b) Construction requirements for steel or aluminum boxes are as...

  20. Dead space and slope indices from the expiratory carbon dioxide tension-volume curve

    NARCIS (Netherlands)

    A.H. Kars (Alice); J.M. Bogaard (Jan); Th. Stijnen (Theo); J. de Vries; A.F.M. Verbraak (Anton); C. Hilvering

    1997-01-01

    textabstractThe slope of phase 3 and three noninvasively determined dead space estimates derived from the expiratory carbon dioxide tension (PCO2) versus volume curve, including the Bohr dead space (VD,Bohr), the Fowler dead space (VD,Fowler) and pre-interface expirate

  1. Application of Optical Flow Sensors for Dead Reckoning, Heading Reference, Obstacle Detection, and Obstacle Avoidance

    Science.gov (United States)

    2015-09-01

    OPTICAL FLOW SENSORS FOR DEAD RECKONING , HEADING REFERENCE, OBSTACLE DETECTION, AND OBSTACLE AVOIDANCE by Tarek M. Nejah September 2015...SENSORS FOR DEAD RECKONING , HEADING REFERENCE, OBSTACLE DETECTION, AND OBSTACLE AVOIDANCE 5. FUNDING NUMBERS 6. AUTHOR(S) Nejah, Tarek M. 7...DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) A novel approach for dead reckoning , heading reference, obstacle detection, and obstacle

  2. 78 FR 16565 - Culturally Significant Objects Imported for Exhibition Determinations: “The Dead Sea Scrolls...

    Science.gov (United States)

    2013-03-15

    ... Culturally Significant Objects Imported for Exhibition Determinations: ``The Dead Sea Scrolls: Life and Faith in Ancient Times'' Formerly Titled ``The Dead Sea Scrolls: Life and Faith in Biblical Times'' ACTION... exhibition ``The Dead Sea Scrolls: Life and Faith in Biblical Times.'' The referenced notice was corrected on...

  3. 78 FR 62354 - Culturally Significant Objects Imported for Exhibition Determinations: “The Dead Sea Scrolls...

    Science.gov (United States)

    2013-10-18

    ... Culturally Significant Objects Imported for Exhibition Determinations: ``The Dead Sea Scrolls: Life and Faith in Ancient Times'' Formerly Titled ``The Dead Sea Scrolls: Life and Faith in Biblical Times'' ACTION... exhibition ``The Dead Sea Scrolls: Life and Faith in Biblical Times.'' The referenced notice was corrected on...

  4. 77 FR 64373 - Culturally Significant Objects Imported for Exhibition Determinations: “The Dead Sea Scrolls...

    Science.gov (United States)

    2012-10-19

    ... Culturally Significant Objects Imported for Exhibition Determinations: ``The Dead Sea Scrolls: Life and Faith in Ancient Times,'' Formerly Titled ``The Dead Sea Scrolls: Life and Faith in Biblical Times... the exhibition ``The Dead Sea Scrolls: Life and Faith in Biblical Times.'' The referenced notice is...

  5. 78 FR 24462 - Culturally Significant Objects Imported for Exhibition; Determinations: “The Dead Sea Scrolls...

    Science.gov (United States)

    2013-04-25

    ... Culturally Significant Objects Imported for Exhibition; Determinations: ``The Dead Sea Scrolls: Life and Faith in Ancient Times'' Formerly Titled ``The Dead Sea Scrolls: Life and Faith in Biblical Times... the exhibition ``The Dead Sea Scrolls: Life and Faith in Biblical Times.'' The referenced notice was...

  6. El Dia de los Muertos -- Libreto. (The Day of the Dead -- Notebook.)

    Science.gov (United States)

    Espinoza, Delia; Lopez, Santiago, III

    On November 2, all Mexican Americans remember their dead as Mexico does on that same day. Called "El Dia de los Muertos" (Day of the Dead), the dead are remembered posthumously with flowers, candles, music, prayers, chants, and wreaths. The people go to cemeteries to clean tombs, lay fresh or artificial flowers on them, and pray for…

  7. Microclimate and habitat heterogeneity as the major drivers of beetle diversity in dead wood

    Science.gov (United States)

    Sebastian Seibold; Claus Bassler; Roland Brandl; Boris Buche; Alexander Szallies; Simon Thorn; Michael D. Ulyshen; Jorg Muller; Christopher Baraloto

    2016-01-01

    1. Resource availability and habitat heterogeneity are principle drivers of biodiversity, but their individual roles often remain unclear since both factors are usually correlated. The biodiversity of species dependent on dead wood could be driven by either resource availability represented by dead-wood amount or habitat heterogeneity characterized by dead-wood...

  8. 9 CFR 309.3 - Dead, dying, disabled, or diseased and similar livestock.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Dead, dying, disabled, or diseased and... AND VOLUNTARY INSPECTION AND CERTIFICATION ANTE-MORTEM INSPECTION § 309.3 Dead, dying, disabled, or diseased and similar livestock. (a) Livestock found to be dead or in a dying condition on the premises of...

  9. Proportional Derivative Control with Inverse Dead-Zone for Pendulum Systems

    OpenAIRE

    Rubio, José de Jesús; Zamudio, Zizilia; Pacheco, Jaime; Mújica Vargas, Dante

    2013-01-01

    A proportional derivative controller with inverse dead-zone is proposed for the control of pendulum systems. The proposed method has the characteristic that the inverse dead-zone is cancelled with the pendulum dead-zone. Asymptotic stability of the proposed technique is guaranteed by the Lyapunov analysis. Simulations of two pendulum systems show the effectiveness of the proposed technique.

  10. Boxing headguard performance in punch machine tests.

    Science.gov (United States)

    McIntosh, Andrew S; Patton, Declan A

    2015-09-01

    The paper presents a novel laboratory method for assessing boxing headguard impact performance. The method is applied to examine the effects of headguards on head impact dynamics and injury risk. A linear impactor was developed, and a range of impacts was delivered to an instrumented Hybrid III head and neck system both with and without an AIBA (Association Internationale de Boxe Amateur)-approved headguard. Impacts at selected speeds between 4.1 and 8.3 m/s were undertaken. The impactor mass was approximately 4 kg and an interface comprising a semirigid 'fist' with a glove was used. The peak contact forces were in the range 1.9-5.9 kN. Differences in head impact responses between the Top Ten AIBA-approved headguard and bare headform in the lateral and forehead tests were large and/or significant. In the 8.3 m/s fist-glove impacts, the mean peak resultant headform accelerations for bare headform tests was approximately 130 g compared with approximately 85 g in the forehead impacts. In the 6.85 m/s bare headform impacts, mean peak resultant angular head accelerations were in the range of 5200-5600 rad/s(2) and almost halved by the headguard. Linear and angular accelerations in 45° forehead and 60° jaw impacts were reduced by the headguard. The data support the opinion that current AIBA headguards can play an important role in reducing the risk of concussion and superficial injury in boxing competition and training. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Not to declare dead someone still alive: Case reports

    Directory of Open Access Journals (Sweden)

    Anđelić Slađana

    2015-01-01

    Full Text Available Introduction. Diagnosing death represents an activity that carries a great deal of public responsibility for medical professionals and is continually exposed to the control of citizens and media. Although this is a taboo subject in medical circles, unfortunately in medical practice there are situations when the physician issues a death diagnosis form without even examining the person or for an already buried person. Such physician’s action is impermissible and it leads to the possibility of professional and criminal law punishment. Case Outline. By giving examples from practice, we wish to point out the need for exceptional caution when confirming and diagnosing death in order to diagnose the true, i.e. rule out apparent death and consequently avoid the mistake of declaring dead someone still alive. Conclusion. When confirming and declaring death, exceptional caution of the physician is necessary so as not to declare dead someone still alive!

  12. Awakening the "Walking Dead": Zombie Pedagogy for Millennials

    Directory of Open Access Journals (Sweden)

    Nancy Dawn Wadsworth

    2017-02-01

    Full Text Available This article lays out the pedagogical benefits of using popular zombie productions, particularly AMC's The Walking Dead, to teach a critical introduction to modern political theory. Based on my undergraduate course: "Political Theory, Climate Change, and the Zombie Apocalypse," the article outlines how The Walking Dead can be used to critique the mythic assumptions built into modern social contract theory; to introduce other political ideologies, including conservatism, anarchism, fascism, and communism; and to consider the political challenges raised by a global problem such as climate change in an increasingly neoliberal environment. Zombie productions are offered as a particularly salient pedagogical tool that can help awaken critical political analysis for the Millennial Generation.

  13. The death effect in literary evaluation: reverence for the dead?

    Science.gov (United States)

    Green, Joseph P; Mohler, Eric W

    It is commonly believed that the value of art and other creative works increases after the death of the artist. In an attempt to examine this so-called death effect we presented a short story to N = 431 undergraduate students asking how much money they would hypothetically spend to purchase a literary work. We experimentally manipulated: 1) whether the author died or moved after publishing a short story, and, 2) the gender of the author. Participants randomly received one of four possible biographical descriptions about the author. We predicted that participants would offer higher purchase prices and subjectively evaluate the work more positively when they believed the author was dead. Results were consistent with this hypothesis perhaps reflecting a certain reverence for the dead. We also found that evaluations of the story were more favorable when the purported gender of the author matched that of the participant.

  14. Pulsed optically pumped atomic clock with zero-dead-time

    Science.gov (United States)

    Lin, Haixiao; Lin, Jinda; Deng, Jianliao; Zhang, Song; Wang, Yuzhu

    2017-12-01

    By alternatively operating two pulsed optically pumped (POP) atomic clocks, the dead time in a single clock can be eliminated, and the local oscillator can be discriminated continuously. A POP atomic clock with a zero-dead-time (ZDT) method is then insensitive to the microwave phase noise. From τ = 0.01 to 1 s, the Allan deviation of the ZDT-POP clock is reduced as nearly τ-1, which is significantly faster than τ-1/2 of a conventional clock. During 1-40 s, the Allan deviation returns to τ-1/2. Moreover, the frequency stability of the ZDT-POP clock is improved by one order of magnitude compared with that of the conventional POP clock. We also analyze the main factors that limit the short-term frequency stability of the POP atomic clock.

  15. The Dead Mother, the Uncanny, and the Holy Ghost

    Directory of Open Access Journals (Sweden)

    Gal Ventura

    2015-01-01

    Full Text Available Recurrent portrayals of dead mothers frequently appeared in French art from 1800 to 1850. This essay focuses on one of the latest manifestations of this image, namely, the French Realist Jules Breton's (1827-1906 painting The Hunger of 1850, in order to examine the psycho-historical elements associated with the mother's death. Through an analysis of the "Uncanny" as formulated by both Ernst Jentsch and Sigmund Freud, we will address the undissolvable link between the structuralization of "homeliness" in the late eighteenth century and the dread it evoked in the early nineteenth century, as two sides of the same coin. We will simultaneously consider the inherent conflictuality embodied by the dead mother according to the French psychoanalyst André Green, who dealt with the experience of "nothingness" that characterizes children of mothers-who-refuse-to-die.

  16. Emerging Role of High-Mobility Group Box 1 (HMGB1) in Liver Diseases

    OpenAIRE

    Chen, Ruochan; Hou, Wen; Zhang, Qiuhong; Kang, Rui; Fan, Xue-Gong; Tang, Daolin

    2013-01-01

    Damage-associated molecular pattern (DAMP) molecules are essential for the initiation of innate inflammatory responses to infection and injury. The prototypic DAMP molecule, high-mobility group box 1 (HMGB1), is an abundant architectural chromosomal protein that has location-specific biological functions: within the nucleus as a DNA chaperone, within the cytosol to sustain autophagy and outside the cell as a DAMP molecule. Recent research indicates that aberrant activation of HMGB1 signaling ...

  17. Design Research: Six Views in a Box

    DEFF Research Database (Denmark)

    2011-01-01

    ways to better understand the consequences of the disease, spread the knowledge to more people and diagnosis the disease as soon as possible. The class was partly sponsored by Johnson & Johnson, an international pharmaceutical company. The students also collaborated with the Danish Alzheimer...... Association. Future designers need competence in co-design. Just as important is the need to establish various formats for how to maintain the research results and make these a valuable asset for further inquiry. Thus, the outcome of the class is a box that can be used by Johnson & Johnson and other...

  18. Development of blanket box structure fabrication technology

    International Nuclear Information System (INIS)

    Mohri, K.; Sato, S.; Kawaguchi, I.; Sato, K.; Kuroda, T.; Hashimoto, T.; Sato, S.; Takatsu, H.

    1995-01-01

    Fabrication studies have been performed for the first wall and blanket box structure in the fusion experimental reactor designed in Japan. The hot isostatic pressing technique has been proposed as one of the most promising candidate methods for fabricating the first wall. This paper describes the trial fabrication of a half-scale mock-up for part of an outboard module near the midplane, without the internal structure of a breeding region, to investigate its feasibility and to clarify technological issues associated with the proposed fabrication technologies. (orig.)

  19. Piracy and Box Office Movie Revenues

    DEFF Research Database (Denmark)

    Peukert, Christian; Claussen, Jörg; Kretschmer, Tobias

    2017-01-01

    In this paper we evaluate the heterogeneous effects of online copyright enforcement. We ask whether the unexpected shutdown of the popular file hosting platform Megaupload had a differential effect on box office revenues of wide-release vs. niche movies. Identification comes from a comparison...... of movies that were available on Megaupload to those that were not. We show that only movies that premiere in a relatively large number of theaters benefitted from the shutdown of Megaupload. The average effect, however, is negative. We provide suggestive evidence that this result is driven by information...

  20. Keller-box method and its application

    CERN Document Server

    Prasad, Kerehalli V

    2014-01-01

    Most of the problems arising in science and engineering are nonlinear. They are inherently difficult to solve. Traditional analytical approximations are valid only for weakly nonlinear problems, and often break down for problems with strong nonlinearity. This book presents the current theoretical developments and applications of Keller-Box method to nonlinear problems. The first half of the bookaddresses basic concepts to understand the theoretical framework for the method. In the second half of the book, the authorsgive a number of examples of coupled nonlinear problems that have been solved

  1. Design Research: Six Views in a Box

    DEFF Research Database (Denmark)

    2011-01-01

    and close relations, and professional caretakers. Alzheimer's destroys brain cells, causing memory loss and problems with thinking and behavior severe enough to affect work, lifelong hobbies and social life. As Alzheimer’s is a fatal disease that affects many people, there is a strong interest in finding...... professional organizations in a user-driven approach to explore and learn what it means to identify and admit that a person has Alzheimer’s. Apart from making contributions to the common box, the students have written reports in which they reflect on their work both in relation to the design research process...

  2. Do Biomimetic Students Think Outside the Box?

    DEFF Research Database (Denmark)

    Lenau, Torben Anker

    2017-01-01

    Biomimetics is a recognized method in ideation for getting access to new and – for the designer – novel knowledge, which hopefully will result in more novel and useful products. But do designers actually find new knowledge, i.e. think outside the box or do they stick to well-known biological...... phenomena? If they concentrate on animals and plants, which they beforehand have knowledge about, it could be expected that solutions will remind of what they would have found without using biomimetics. To investigate this question, the empirical results from a university course in biomimetics have been...

  3. Test procedure for boxed waste assay system

    International Nuclear Information System (INIS)

    Wachter, J.

    1994-01-01

    This document, prepared by Los Alamos National Laboratory's NMT-4 group, details the test methodology and requirements for Acceptance/Qualification testing of a Boxed Waste Assay System (BWAS) designed and constructed by Pajarito Scientific Corporation. Testing of the BWAS at the Plutonium Facility (TA55) at Los Alamos National Laboratory will be performed to ascertain system adherence to procurement specification requirements. The test program shall include demonstration of conveyor handling capabilities, gamma ray energy analysis, and imaging passive/active neutron accuracy and sensitivity. Integral to these functions is the system's embedded operating and data reduction software

  4. AntReckoning: Dead Reckoning using Interest Modeling by Pheromones

    OpenAIRE

    Yahyavi , Amir; Huguenin , Kévin; Kemme , Bettina

    2011-01-01

    International audience; In games, the goals and interests of players are key factors in their behavior. However, techniques used by networked games to cope with infrequent updates and message loss, such as dead reckoning, estimate a player's movements based on previous observations only. The estimations are typically done using dynamics of motion, taking only inertia and external factors (e.g., gravity, wind) into account while completely ignoring the player's goals (e.g., chasing other playe...

  5. Strong tracking adaptive Kalman filters for underwater vehicle dead reckoning

    Science.gov (United States)

    Xiao, Kun; Fang, Shao-Ji; Pang, Yong-Jie

    2007-06-01

    To impove underwater vehicle dead reckoning, a developed strong tracking adaptive kalman filter is proposed. The filter is improved with an additional adaptive factor and an estimator of measurement noise covariance. Since the magnitude of fading factor is changed adaptively, the tracking ability of the filter is still enhanced in low velocity condition of underwater vehicles. The results of simulation tests prove the presented filter effective.

  6. Interest Modeling in Games: The Case of Dead Reckoning

    OpenAIRE

    Yahyavi, Amir; Huguenin, Kévin; Kemme, Bettina

    2013-01-01

    Special Issue on Network and Systems Support for Games; International audience; In games, the goals and interests of players are key factors in their behavior. However, techniques used by networked games to cope with infrequent updates and message loss, such as dead reckoning, estimate a player's movements based mainly on previous observations. The estimations are typically made by using dynamics of motion, taking only inertia and some external factors (e.g., gravity, wind) into account while...

  7. Vector Graph Assisted Pedestrian Dead Reckoning Using an Unconstrained Smartphone

    OpenAIRE

    Qian, Jiuchao; Pei, Ling; Ma, Jiabin; Ying, Rendong; Liu, Peilin

    2015-01-01

    The paper presents a hybrid indoor positioning solution based on a pedestrian dead reckoning (PDR) approach using built-in sensors on a smartphone. To address the challenges of flexible and complex contexts of carrying a phone while walking, a robust step detection algorithm based on motion-awareness has been proposed. Given the fact that step length is influenced by different motion states, an adaptive step length estimation algorithm based on motion recognition is developed. Heading estimat...

  8. Thermodynamics of the dead zone inner edge in protoplanetary disks

    International Nuclear Information System (INIS)

    Faure, Julien

    2014-01-01

    The dead zone, a quiescent region enclosed in the turbulent flow of a protoplanetary disk, seems to be a promising site for planet formation. Indeed, the development of a density maximum at the dead zone inner edge, that has the property to trap the infalling dust, is a natural outcome of the accretion mismatch at this interface. Moreover, the flow here may be unstable and organize itself into vortical structures that efficiently collect dust grains. The inner edge location is however loosely constrained. In particular, it depends on the thermodynamical prescriptions of the disk model that is considered. It has been recently proposed that the inner edge is not static and that the variations of young stars accretion luminosity are the signature of this interface displacements. This thesis address the question of the impact of the gas thermodynamics onto its dynamics around the dead zone inner edge. MHD simulations including the complex interplay between thermodynamical processes and the dynamics confirmed the dynamical behaviour of the inner edge. A first measure of the interface velocity has been realised. This result has been compared to the predictions of a mean field model. It revealed the crucial role of the energy transport by density waves excited at the interface. These simulations also exhibit a new intriguing phenomenon: vortices forming at the interface follow a cycle of formation-migration-destruction. This vortex cycle may compromise the formation of planetesimals at the inner edge. This thesis claims that thermodynamical processes are at the heart of how the region around the dead zone inner edge in protoplanetary disks works. (author) [fr

  9. The conformational state of the nucleosome entry–exit site modulates TATA box-specific TBP binding

    Science.gov (United States)

    Hieb, Aaron R.; Gansen, Alexander; Böhm, Vera; Langowski, Jörg

    2014-01-01

    The TATA binding protein (TBP) is a critical transcription factor used for nucleating assembly of the RNA polymerase II machinery. TBP binds TATA box elements with high affinity and kinetic stability and in vivo is correlated with high levels of transcription activation. However, since most promoters use less stable TATA-less or TATA-like elements, while also competing with nucleosome occupancy, further mechanistic insight into TBP's DNA binding properties and ability to access chromatin is needed. Using bulk and single-molecule FRET, we find that TBP binds a minimal consensus TATA box as a two-state equilibrium process, showing no evidence for intermediate states. However, upon addition of flanking DNA sequence, we observe non-specific cooperative binding to multiple DNA sites that compete for TATA-box specificity. Thus, we conclude that TBP binding is defined by a branched pathway, wherein TBP initially binds with little sequence specificity and is thermodynamically positioned by its kinetic stability to the TATA box. Furthermore, we observed the real-time access of TBP binding to TATA box DNA located within the DNA entry–exit site of the nucleosome. From these data, we determined salt-dependent changes in the nucleosome conformation regulate TBP's access to the TATA box, where access is highly constrained under physiological conditions, but is alleviated by histone acetylation and TFIIA. PMID:24829456

  10. The conformational state of the nucleosome entry-exit site modulates TATA box-specific TBP binding.

    Science.gov (United States)

    Hieb, Aaron R; Gansen, Alexander; Böhm, Vera; Langowski, Jörg

    2014-07-01

    The TATA binding protein (TBP) is a critical transcription factor used for nucleating assembly of the RNA polymerase II machinery. TBP binds TATA box elements with high affinity and kinetic stability and in vivo is correlated with high levels of transcription activation. However, since most promoters use less stable TATA-less or TATA-like elements, while also competing with nucleosome occupancy, further mechanistic insight into TBP's DNA binding properties and ability to access chromatin is needed. Using bulk and single-molecule FRET, we find that TBP binds a minimal consensus TATA box as a two-state equilibrium process, showing no evidence for intermediate states. However, upon addition of flanking DNA sequence, we observe non-specific cooperative binding to multiple DNA sites that compete for TATA-box specificity. Thus, we conclude that TBP binding is defined by a branched pathway, wherein TBP initially binds with little sequence specificity and is thermodynamically positioned by its kinetic stability to the TATA box. Furthermore, we observed the real-time access of TBP binding to TATA box DNA located within the DNA entry-exit site of the nucleosome. From these data, we determined salt-dependent changes in the nucleosome conformation regulate TBP's access to the TATA box, where access is highly constrained under physiological conditions, but is alleviated by histone acetylation and TFIIA. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Seismic stability of a standalone glove box structure

    International Nuclear Information System (INIS)

    Saraswat, A.; Reddy, G.R.; Ghosh, S.; Ghosh, A.K.; Kumar, Arun

    2014-01-01

    Highlights: • Glove box is a leak tight, safety related structure used for handling radiotoxic materials. • To study the seismic performance of a freestanding glove box, extensive shake table testing has been carried out. • Glove box maintained structural integrity and leak tightness up to design basis earthquake loading. • Detailed three-dimensional finite element model of the structure is developed and analyzed by using direct time integration methods. • Simplified numerical method is proposed and successfully applied, to quickly estimate sliding displacement and determine upper bounds for it. - Abstract: In a nuclear fuel cycle facility, radiotoxic materials are being handled in freestanding leak tight enclosures called glove boxes (GBs). These glove boxes act as a primary confinement for the radiotoxic materials. Glove boxes are designed as per codal requirements for class I component. They are designed to withstand extreme level of earthquake loading with a return period of 10,000 years. To evaluate seismic performance of the glove box, there is a need to check the stability (sliding and overturning), structural integrity (stresses and strains) and leak tightness under earthquake loading. Extensive shake table experiments were conducted on a single standalone glove box. Actual laboratory conditions were simulated during testing to check the response. After extensive shake table testing, glove box structure was also analyzed using finite element (FE) software. Detailed three-dimensional model of glove box structure was developed and analyzed using nonlinear time history method. It was observed that finite element methods could be utilized to accurately predict dynamic response of glove box structure. This paper discusses the details and results of shake table testing and methodology used for modelling and analysing freestanding glove box structure under seismic loading. In addition, simplified numerical procedure, developed using energy conservation

  12. Seismic stability of a standalone glove box structure

    Energy Technology Data Exchange (ETDEWEB)

    Saraswat, A., E-mail: anupams@barc.gov.in [Bhabha Atomic Research Centre, Mumbai (India); Reddy, G.R. [Bhabha Atomic Research Centre, Mumbai (India); Ghosh, S. [Indian Institute of Technology Bombay, Mumbai (India); Ghosh, A.K.; Kumar, Arun [Bhabha Atomic Research Centre, Mumbai (India)

    2014-09-15

    Highlights: • Glove box is a leak tight, safety related structure used for handling radiotoxic materials. • To study the seismic performance of a freestanding glove box, extensive shake table testing has been carried out. • Glove box maintained structural integrity and leak tightness up to design basis earthquake loading. • Detailed three-dimensional finite element model of the structure is developed and analyzed by using direct time integration methods. • Simplified numerical method is proposed and successfully applied, to quickly estimate sliding displacement and determine upper bounds for it. - Abstract: In a nuclear fuel cycle facility, radiotoxic materials are being handled in freestanding leak tight enclosures called glove boxes (GBs). These glove boxes act as a primary confinement for the radiotoxic materials. Glove boxes are designed as per codal requirements for class I component. They are designed to withstand extreme level of earthquake loading with a return period of 10,000 years. To evaluate seismic performance of the glove box, there is a need to check the stability (sliding and overturning), structural integrity (stresses and strains) and leak tightness under earthquake loading. Extensive shake table experiments were conducted on a single standalone glove box. Actual laboratory conditions were simulated during testing to check the response. After extensive shake table testing, glove box structure was also analyzed using finite element (FE) software. Detailed three-dimensional model of glove box structure was developed and analyzed using nonlinear time history method. It was observed that finite element methods could be utilized to accurately predict dynamic response of glove box structure. This paper discusses the details and results of shake table testing and methodology used for modelling and analysing freestanding glove box structure under seismic loading. In addition, simplified numerical procedure, developed using energy conservation

  13. Making the weight: a case study from professional boxing.

    Science.gov (United States)

    Morton, James P; Robertson, Colin; Sutton, Laura; MacLaren, Don P M

    2010-02-01

    Professional boxing is a combat sport categorized into a series of weight classes. Given the sport's underpinning culture, boxers' typical approach to "making weight" is usually via severe acute and/or chronic energy restriction and dehydration. Such practices have implications for physical performance and also carry health risks. This article provides a case-study account outlining a more structured and gradual approach to helping a professional male boxer make weight for the 59-kg superfeatherweight division. Over a 12-week period, the client athlete adhered to a daily diet approximately equivalent to his resting metabolic rate (6-7 MJ; 40% carbohydrate, 38% protein, 22% fat). Average body-mass loss was 0.9 + or - 0.4 kg/wk, equating to a total loss of 9.4 kg. This weight loss resulted in a decrease in percent body fat from 12.1% to 7.0%. In the 30 hr between weigh-in and competition, the client consumed a high-carbohydrate diet (12 g/kg body mass) supported by appropriate hydration strategies and subsequently entered the ring at a fighting weight of 63.2 kg. This nutritional strategy represented a major change in the client's habitual weight-making practices and did not rely on any form of intended dehydration during the training period or before weighing in. The intervention demonstrates that a more gradual approach to making weight in professional boxing can be successfully achieved via a combination of restricted energy intake and increased energy expenditure, providing there is willingness on the part of the athlete and coaches involved to adopt novel practices.

  14. Evolution and divergence of SBP-box genes in land plants.

    Science.gov (United States)

    Zhang, Shu-Dong; Ling, Li-Zhen; Yi, Ting-Shuang

    2015-10-14

    Squamosa promoter binding protein (SBP)-box family genes encode plant-specific transcription factors that control many important biological functions, including phase transition, inflorescence branching, fruit ripening, and copper homeostasis. Nevertheless, the evolutionary patterns of SBP-box genes and evolutionary forces driving them are still not well understood. 104 SBP-box gene candidates of five representative land plants were obtained from Phytozome database (v10.3). Phylogenetic combined with gene structure analyses were used to identify SBP-box gene lineages in land plants. Gene copy number and the sequence and structure features were then compared among these different SBP-box lineages. Selection analysis, relative rate tests and expression divergence were finally used to interpret the evolutionary relationships and divergence of SBP-box genes in land plants. We investigated 104 SBP-box genes from moss, Arabidopsis, poplar, rice, and maize. These genes are divided into group I and II, and the latter is further divided into two subgroups (subgroup II-1 and II-2) based on phylogenetic analysis. Interestingly, subgroup II-1 genes have similar sequence and structural features to group I genes, whereas subgroup II-2 genes exhibit intrinsic differences on these features, including high copy numbers and the presence of miR156/miR529 regulation. Further analyses indicate that subgroup II-1 genes are constrained by stronger purifying selection and evolve at a lower substitution rate than II-2 genes, just as group I genes do when compared to II genes. Among subgroup II-2 genes, miR156 targets evolve more rapidly than miR529 targets and experience comparatively relaxed purifying selection. These results suggest that group I and subgroup II-1 genes under strong selective constraint are conserved. By contrast, subgroup II-2 genes evolve under relaxed purifying selection and have diversified through gene copy duplications and changes in miR156/529 regulation, which

  15. Cooperation Between Dead Reckoning (Path Integration) and External Position Cues

    Science.gov (United States)

    Etienne, Ariane S.; Maurer, Roland; Berlie, Joëlle; Derivaz, Valérie; Georgakopoulos, Joséphine; Griffin, Andrea; Rowe, Tiffany

    Dead reckoning (also called path integration) is the process by which a navigating organism derives its current position relative to an Earthbound reference point from its own locomotion. Dead reckoning requires the continuous estimation of changes in direction and location through self-generated signals and the computation of position on the basis of these signals.(i) Hymenopterous insects measure rotations and translations mainly with the help of optical references such as the Sun and translational visual flow. By contrast, mammals are able to estimate their position on the basis of purely 'internal' information; that is, signals generated in the vestibular system by inertial forces, somatosensory feedback, and efference copies (copies of central commands that control the performance of rotations and translations). Obviously, the assessment of the angular and linear components of locomotion is much more precise if it is assisted by external references than if this is not the case.(ii) Only man-made dead reckoning systems yield precise position information through the twofold integration over time of inertial signals deriving from angular and linear acceleration. On the biological level, all species tested so far seem to rely on a simplified form of path 'integration': in certain test situations, arthropods and mammals (including humans) commit similar systematic errors. This suggests that species from unrelated taxa update position according to a similar algorithm.

  16. Water Quality Modeling in the Dead End Sections of Drinking ...

    Science.gov (United States)

    Dead-end sections of drinking water distribution networks are known to be problematic zones in terms of water quality degradation. Extended residence time due to water stagnation leads to rapid reduction of disinfectant residuals allowing the regrowth of microbial pathogens. Water quality models developed so far apply spatial aggregation and temporal averaging techniques for hydraulic parameters by assigning hourly averaged water demands to the main nodes of the network. Although this practice has generally resulted in minimal loss of accuracy for the predicted disinfectant concentrations in main water transmission lines, this is not the case for the peripheries of a distribution network. This study proposes a new approach for simulating disinfectant residuals in dead end pipes while accounting for both spatial and temporal variability in hydraulic and transport parameters. A stochastic demand generator was developed to represent residential water pulses based on a non-homogenous Poisson process. Dispersive solute transport was considered using highly dynamic dispersion rates. A genetic algorithm was used to calibrate the axial hydraulic profile of the dead-end pipe based on the different demand shares of the withdrawal nodes. A parametric sensitivity analysis was done to assess the model performance under variation of different simulation parameters. A group of Monte-Carlo ensembles was carried out to investigate the influence of spatial and temporal variations

  17. Gulf of Mexico dead zone - 1000 year record

    Science.gov (United States)

    Osterman, L.E.; Poore, R.Z.; Swarzenski, P.W.

    2010-01-01

    An area of oxygen-depleted bottom- and subsurfacewater (hypoxia = dissolved oxygen Since systematic measurement of the extent of the dead zone was begun in 1985, the overall pattern indicates that the area of the dead zone is increasing. Several studies have concluded that the expansion of the Louisiana shelf dead zone is related to increased nutrients (primarily nitrogen, but possibly also phosphorous) in the Mississippi River drainage basin and is responsible for the degradation of Gulf of Mexico marine habitats. The goal of this research is to augment information on the recent expansion of Louisiana shelf hypoxia and to investigate the temporal and geographic extent of the lowoxygen bottom-water conditions prior to 1985 in sediment cores collected from the Louisiana shelf. We use a specific low-oxygen faunal proxy termed the PEB index based on the cumulative percentage of three foraminifers (= % Protononion atlanticum, + % Epistominella vitrea, + % Buliminella morgani) that has been shown statistically to represent the modern seasonal Louisiana hypoxia zone. Our hypothesis is that the increased relative abundance of PEB species in dated sediment cores accurately tracks past seasonal low-oxygen conditions on the Louisiana shelf.

  18. Cdc20 mediates D-box-dependent degradation of Sp100

    International Nuclear Information System (INIS)

    Wang, Ran; Li, Ke-min; Zhou, Cai-hong; Xue, Jing-lun; Ji, Chao-neng; Chen, Jin-zhong

    2011-01-01

    Highlights: ► Cdc20 is a co-activator of APC/C complex. ► Cdc20 recruits Sp100 and mediates its degradation. ► The D-box of Sp100 is required for Cdc20-mediated degradation. ► Sp100 expresses consistently at both the mRNA and protein levels in cell cycle. -- Abstract: Cdc20 is a co-activator of the anaphase-promoting complex/cyclosome (APC/C complex), which recruits substrates at particular phases of the cell cycle and mediates their degradation. Sp100 is a PML-NB scaffold protein, which localizes to nuclear particles during interphase and disperses from them during mitosis, participates in viral resistance, transcriptional regulation, and apoptosis. However, its metabolism during the cell cycle has not yet been fully characterized. We found a putative D-box in Sp100 using the Eukaryotic Linear Motif (ELM) predictor database. The putative D-box of Sp100 was verified by mutational analysis. Overexpression of Cdc20 resulted in decreased levels of both endogenous Sp100 protein and overexpressed Sp100 mRNA in HEK 293 cells. Only an overexpressed D-box deletion mutant of Sp100 accumulated in HEK293 cells that also overexpressed Cdc20. Cdc20 knockdown by cdc20 specific siRNA resulted in increased Sp100 protein levels in cells. Furthermore, we discovered that the Cdc20 mediated degradation of Sp100 is diminished by the proteasome inhibitor MG132, which suggests that the ubiquitination pathway is involved in this process. However, unlike the other Cdc20 substrates, which display oscillating protein levels, the level of Sp100 protein remains constant throughout the cell cycle. Additionally, both overexpression and knockdown of endogenous Sp100 had no effect on the cell cycle. Our results suggested that sp100 is a novel substrate of Cdc20 and it is degraded by the ubiquitination pathway. The intact D-box of Sp100 was necessary for this process. These findings expand our knowledge of both Sp100 and Cdc20 as well as their role in ubiquitination.

  19. Comprehensive study in the inhibitory effect of berberine on gene transcription, including TATA box.

    Science.gov (United States)

    Wang, Yugang; Kheir, Michael M; Chai, Yushuang; Hu, Jun; Xing, Dongming; Lei, Fan; Du, Lijun

    2011-01-01

    Berberine (BBR) is an established natural DNA intercalator with numerous pharmacological functions. However, currently there are neither detailed reports concerning the distribution of this alkaloid in living cells nor reports concerning the relationship between BBR's association with DNA and the function of DNA. Here we report that the distribution of BBR within the nucleus can be observed 30 minutes after drug administration, and that the content of berberine in the nucleus peaks at around 4 µmol, which is twelve hours after drug administration. The spatial conformation of DNA and chromatin was altered immediately after their association with BBR. Moreover, this association can effectively suppress the transcription of DNA in living cell systems and cell-free systems. Electrophoretic mobility shift assays (EMSA) demonstrated further that BBR can inhibit the association between the TATA binding protein (TBP) and the TATA box in the promoter, and this finding was also attained in living cells by chromatin immunoprecipitation (ChIP). Based on results from this study, we hypothesize that berberine can suppress the transcription of DNA in living cell systems, especially suppressing the association between TBP and the TATA box by binding with DNA and, thus, inhibiting TATA box-dependent gene expression in a non-specific way. This novel study has significantly expanded the sphere of knowledge concerning berberine's pharmacological effects, beginning at its paramount initial interaction with the TATA box.

  20. Reconciling White-Box and Black-Box Perspectives on Behavioral Self-adaptation

    DEFF Research Database (Denmark)

    Bruni, Roberto; Corradini, Andrea; Gadducci, Fabio

    2015-01-01

    This paper proposes to reconcile two perspectives on behavioral adaptation commonly taken at different stages of the engineering of autonomic computing systems. Requirements engineering activities often take a black-box perspective: A system is considered to be adaptive with respect to an environ...