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Sample records for component rrp6p reveals

  1. Structure of the nuclear exosome component Rrp6p reveals an interplay between the active site and the HRDC domain

    DEFF Research Database (Denmark)

    Midtgaard, Søren Fuglsang; Assenholt, Jannie; Jonstrup, Anette Thyssen

    2006-01-01

    The multisubunit eukaryotic exosome is an essential RNA processing and degradation machine. In its nuclear form, the exosome associates with the auxiliary factor Rrp6p, which participates in both RNA processing and degradation reactions. The crystal structure of Saccharomyces cerevisiae Rrp6p...... ribonucleotides and their bases. Finally, in vivo mutational studies show the importance of the domain contacts for the processing function of Rrp6p and highlight fundamental differences between the protein and its prokaryotic RNase D counterparts....

  2. Structural analysis of the yeast exosome Rrp6p–Rrp47p complex by small-angle X-ray scattering

    Energy Technology Data Exchange (ETDEWEB)

    Dedic, Emil; Seweryn, Paulina; Jonstrup, Anette Thyssen; Flygaard, Rasmus Koch [Centre for mRNP Biogenesis and Metabolism, Gustav Wieds Vej 10c, Aarhus University, DK-8000 Aarhus C (Denmark); Department of Molecular Biology and Genetics, Gustav Wieds Vej 10c, Aarhus University, DK-8000 Aarhus C (Denmark); Fedosova, Natalya U. [Department of Biomedicine, Ole Worms Allé 6, Aarhus University, DK-8000 Aarhus C (Denmark); Hoffmann, Søren Vrønning [Institute for Storage Ring Facilities (ISA), Department of Physics and Astronomy, Ny Munkegade 120, Aarhus University, DK-8000 Aarhus C (Denmark); Boesen, Thomas [Centre for Membrane Pumps in Cells and Disease – PUMPKIN, Gustav Wieds Vej 10c, Aarhus University, DK-8000 Aarhus C (Denmark); Department of Molecular Biology and Genetics, Gustav Wieds Vej 10c, Aarhus University, DK-8000 Aarhus C (Denmark); Brodersen, Ditlev Egeskov, E-mail: deb@mb.au.dk [Centre for mRNP Biogenesis and Metabolism, Gustav Wieds Vej 10c, Aarhus University, DK-8000 Aarhus C (Denmark); Department of Molecular Biology and Genetics, Gustav Wieds Vej 10c, Aarhus University, DK-8000 Aarhus C (Denmark)

    2014-07-18

    Highlights: • We show that S. cerevisiae Rrp6p and Rrp47p stabilise each other in vitro. • We determine molecular envelopes of the Rrp6p–Rrp47p complex by SAXS. • Rrp47p binds at the top of the Rrp6p exonuclease domain. • Rrp47p modulates the activity of Rrp6p on a variety of RNA substrates. • Rrp47p does not affect RNA affinity by Rrp6p. - Abstract: The RNase D-type 3′–5′ exonuclease Rrp6p from Saccharomyces cerevisiae is a nuclear-specific cofactor of the RNA exosome and associates in vivo with Rrp47p (Lrp1p). Here, we show using biochemistry and small-angle X-ray scattering (SAXS) that Rrp6p and Rrp47p associate into a stable, heterodimeric complex with an elongated shape consistent with binding of Rrp47p to the nuclease domain and opposite of the HRDC domain of Rrp6p. Rrp47p reduces the exonucleolytic activity of Rrp6p on both single-stranded and structured RNA substrates without significantly altering the affinity towards RNA or the ability of Rrp6p to degrade RNA secondary structure.

  3. Structural analysis of the yeast exosome Rrp6p–Rrp47p complex by small-angle X-ray scattering

    International Nuclear Information System (INIS)

    Dedic, Emil; Seweryn, Paulina; Jonstrup, Anette Thyssen; Flygaard, Rasmus Koch; Fedosova, Natalya U.; Hoffmann, Søren Vrønning; Boesen, Thomas; Brodersen, Ditlev Egeskov

    2014-01-01

    Highlights: • We show that S. cerevisiae Rrp6p and Rrp47p stabilise each other in vitro. • We determine molecular envelopes of the Rrp6p–Rrp47p complex by SAXS. • Rrp47p binds at the top of the Rrp6p exonuclease domain. • Rrp47p modulates the activity of Rrp6p on a variety of RNA substrates. • Rrp47p does not affect RNA affinity by Rrp6p. - Abstract: The RNase D-type 3′–5′ exonuclease Rrp6p from Saccharomyces cerevisiae is a nuclear-specific cofactor of the RNA exosome and associates in vivo with Rrp47p (Lrp1p). Here, we show using biochemistry and small-angle X-ray scattering (SAXS) that Rrp6p and Rrp47p associate into a stable, heterodimeric complex with an elongated shape consistent with binding of Rrp47p to the nuclease domain and opposite of the HRDC domain of Rrp6p. Rrp47p reduces the exonucleolytic activity of Rrp6p on both single-stranded and structured RNA substrates without significantly altering the affinity towards RNA or the ability of Rrp6p to degrade RNA secondary structure

  4. An Interaction between RRP6 and SU(VAR)3-9 Targets RRP6 to Heterochromatin and Contributes to Heterochromatin Maintenance in Drosophila melanogaster

    Science.gov (United States)

    Eberle, Andrea B.; Jordán-Pla, Antonio; Gañez-Zapater, Antoni; Hessle, Viktoria; Silberberg, Gilad; von Euler, Anne; Silverstein, Rebecca A.; Visa, Neus

    2015-01-01

    RNA surveillance factors are involved in heterochromatin regulation in yeast and plants, but less is known about the possible roles of ribonucleases in the heterochromatin of animal cells. Here we show that RRP6, one of the catalytic subunits of the exosome, is necessary for silencing heterochromatic repeats in the genome of Drosophila melanogaster. We show that a fraction of RRP6 is associated with heterochromatin, and the analysis of the RRP6 interaction network revealed physical links between RRP6 and the heterochromatin factors HP1a, SU(VAR)3-9 and RPD3. Moreover, genome-wide studies of RRP6 occupancy in cells depleted of SU(VAR)3-9 demonstrated that SU(VAR)3-9 contributes to the tethering of RRP6 to a subset of heterochromatic loci. Depletion of the exosome ribonucleases RRP6 and DIS3 stabilizes heterochromatic transcripts derived from transposons and repetitive sequences, and renders the heterochromatin less compact, as shown by micrococcal nuclease and proximity-ligation assays. Such depletion also increases the amount of HP1a bound to heterochromatic transcripts. Taken together, our results suggest that SU(VAR)3-9 targets RRP6 to a subset of heterochromatic loci where RRP6 degrades chromatin-associated non-coding RNAs in a process that is necessary to maintain the packaging of the heterochromatin. PMID:26389589

  5. The exosome component Rrp6 is required for RNA polymerase II termination at specific targets of the Nrd1-Nab3 pathway.

    Directory of Open Access Journals (Sweden)

    Melanie J Fox

    Full Text Available The exosome and its nuclear specific subunit Rrp6 form a 3'-5' exonuclease complex that regulates diverse aspects of RNA biology including 3' end processing and degradation of a variety of noncoding RNAs (ncRNAs and unstable transcripts. Known targets of the nuclear exosome include short (<1000 bp RNAPII transcripts such as small noncoding RNAs (snRNAs, cryptic unstable transcripts (CUTs, and some stable unannotated transcripts (SUTs that are terminated by an Nrd1, Nab3, and Sen1 (NNS dependent mechanism. NNS-dependent termination is coupled to RNA 3' end processing and/or degradation by the Rrp6/exosome in yeast. Recent work suggests Nrd1 is necessary for transcriptome surveillance, regulating promoter directionality and suppressing antisense transcription independently of, or prior to, Rrp6 activity. It remains unclear whether Rrp6 is directly involved in termination; however, Rrp6 has been implicated in the 3' end processing and degradation of ncRNA transcripts including CUTs. To determine the role of Rrp6 in NNS termination globally, we performed RNA sequencing (RNA-Seq on total RNA and perform ChIP-exo analysis of RNA Polymerase II (RNAPII localization. Deletion of RRP6 promotes hyper-elongation of multiple NNS-dependent transcripts resulting from both improperly processed 3' RNA ends and faulty transcript termination at specific target genes. The defects in RNAPII termination cause transcriptome-wide changes in mRNA expression through transcription interference and/or antisense repression, similar to previously reported effects of depleting Nrd1 from the nucleus. Elongated transcripts were identified within all classes of known NNS targets with the largest changes in transcription termination occurring at CUTs. Interestingly, the extended transcripts that we have detected in our studies show remarkable similarity to Nrd1-unterminated transcripts at many locations, suggesting that Rrp6 acts with the NNS complex globally to promote

  6. Structure and reconstitution of yeast Mpp6-nuclear exosome complexes reveals that Mpp6 stimulates RNA decay and recruits the Mtr4 helicase

    Energy Technology Data Exchange (ETDEWEB)

    Wasmuth, Elizabeth V. [Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States; Zinder, John C. [Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States; Tri-Institutional Training Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, United States; Zattas, Dimitrios [Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States; Das, Mom [Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States; Lima, Christopher D. [Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States; Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, United States

    2017-07-25

    <p>Nuclear RNA exosomes catalyze a range of RNA processing and decay activities that are coordinated in part by cofactors, including Mpp6, Rrp47, and the Mtr4 RNA helicase. Mpp6 interacts with the nine-subunit exosome core, while Rrp47 stabilizes the exoribonuclease Rrp6 and recruits Mtr4, but it is less clear if these cofactors work together. Using biochemistry with Saccharomyces cerevisiae proteins, we show that Rrp47 and Mpp6 stimulate exosome-mediated RNA decay, albeit with unique dependencies on elements within the nuclear exosome. Mpp6-exosomes can recruit Mtr4, while Mpp6 and Rrp47 each contribute to Mtr4-dependent RNA decay, with maximal Mtr4-dependent decay observed with both cofactors. The 3.3 Å structure of a twelve-subunit nuclear Mpp6 exosome bound to RNA shows the central region of Mpp6 bound to the exosome core, positioning its Mtr4 recruitment domain next to Rrp6 and the exosome central channel. Genetic analysis reveals interactions that are largely consistent with our model.p>

  7. Identification of karyopherins involved in the nuclear import of RNA exosome subunit Rrp6 in Saccharomyces cerevisiae.

    Science.gov (United States)

    Gonzales-Zubiate, Fernando A; Okuda, Ellen K; Da Cunha, Julia P C; Oliveira, Carla Columbano

    2017-07-21

    The exosome is a conserved multiprotein complex essential for RNA processing and degradation. The nuclear exosome is a key factor for pre-rRNA processing through the activity of its catalytic subunits, Rrp6 and Rrp44. In Saccharomyces cerevisiae , Rrp6 is exclusively nuclear and has been shown to interact with exosome cofactors. With the aim of analyzing proteins associated with the nuclear exosome, in this work, we purified the complex with Rrp6-TAP, identified the co-purified proteins by mass spectrometry, and found karyopherins to be one of the major groups of proteins enriched in the samples. By investigating the biological importance of these protein interactions, we identified Srp1, Kap95, and Sxm1 as the most important karyopherins for Rrp6 nuclear import and the nuclear localization signals recognized by them. Based on the results shown here, we propose a model of multiple pathways for the transport of Rrp6 to the nucleus. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. The exosome component Rrp6 is required for RNA polymerase II termination at specific targets of the Nrd1-Nab3 pathway.

    Science.gov (United States)

    Fox, Melanie J; Gao, Hongyu; Smith-Kinnaman, Whitney R; Liu, Yunlong; Mosley, Amber L

    2015-01-01

    The exosome and its nuclear specific subunit Rrp6 form a 3'-5' exonuclease complex that regulates diverse aspects of RNA biology including 3' end processing and degradation of a variety of noncoding RNAs (ncRNAs) and unstable transcripts. Known targets of the nuclear exosome include short (Polymerase II (RNAPII) localization. Deletion of RRP6 promotes hyper-elongation of multiple NNS-dependent transcripts resulting from both improperly processed 3' RNA ends and faulty transcript termination at specific target genes. The defects in RNAPII termination cause transcriptome-wide changes in mRNA expression through transcription interference and/or antisense repression, similar to previously reported effects of depleting Nrd1 from the nucleus. Elongated transcripts were identified within all classes of known NNS targets with the largest changes in transcription termination occurring at CUTs. Interestingly, the extended transcripts that we have detected in our studies show remarkable similarity to Nrd1-unterminated transcripts at many locations, suggesting that Rrp6 acts with the NNS complex globally to promote transcription termination in addition to 3' end RNA processing and/or degradation at specific targets.

  9. The Campylobacter jejuni MarR-like transcriptional regulators RrpA and RrpB both influence bacterial responses to oxidative and aerobic stresses.

    Science.gov (United States)

    Gundogdu, Ozan; da Silva, Daiani T; Mohammad, Banaz; Elmi, Abdi; Mills, Dominic C; Wren, Brendan W; Dorrell, Nick

    2015-01-01

    The ability of the human intestinal pathogen Campylobacter jejuni to respond to oxidative stress is central to bacterial survival both in vivo during infection and in the environment. Re-annotation of the C. jejuni NCTC11168 genome revealed the presence of two MarR-type transcriptional regulators Cj1546 and Cj1556, originally annotated as hypothetical proteins, which we have designated RrpA and RrpB (regulator of response to peroxide) respectively. Previously we demonstrated a role for RrpB in both oxidative and aerobic (O2) stress and that RrpB was a DNA binding protein with auto-regulatory activity, typical of MarR-type transcriptional regulators. In this study, we show that RrpA is also a DNA binding protein and that a rrpA mutant in strain 11168H exhibits increased sensitivity to hydrogen peroxide oxidative stress. Mutation of either rrpA or rrpB reduces catalase (KatA) expression. However, a rrpAB double mutant exhibits higher levels of resistance to hydrogen peroxide oxidative stress, with levels of KatA expression similar to the wild-type strain. Mutation of either rrpA or rrpB also results in a reduction in the level of katA expression, but this reduction was not observed in the rrpAB double mutant. Neither the rrpA nor rrpB mutant exhibits any significant difference in sensitivity to either cumene hydroperoxide or menadione oxidative stresses, but both mutants exhibit a reduced ability to survive aerobic (O2) stress, enhanced biofilm formation and reduced virulence in the Galleria mellonella infection model. The rrpAB double mutant exhibits wild-type levels of biofilm formation and wild-type levels of virulence in the G mellonella infection model. Together these data indicate a role for both RrpA and RrpB in the C. jejuni peroxide oxidative and aerobic (O2) stress responses, enhancing bacterial survival in vivo and in the environment.

  10. The Campylobacter jejuni MarR-like transcriptional regulators RrpA and RrpB both influence bacterial responses to oxidative and aerobic stresses

    Directory of Open Access Journals (Sweden)

    Ozan eGundogdu

    2015-07-01

    Full Text Available The ability of the human intestinal pathogen Campylobacter jejuni to respond to oxidative stress is central to bacterial survival both in vivo during infection and in the environment. Re-annotation of the C. jejuni NCTC11168 genome revealed the presence of two MarR-type transcriptional regulators Cj1546 and Cj1556, originally annotated as hypothetical proteins, which we have designated RrpA and RrpB (regulator of response to peroxide respectively. Previously we demonstrated a role for RrpB in both oxidative and aerobic (O2 stress and that RrpB was a DNA binding protein with auto-regulatory activity, typical of MarR-type transcriptional regulators. In this study, we show that RrpA is also a DNA binding protein and that a rrpA mutant in strain 11168H exhibits increased sensitivity to hydrogen peroxide oxidative stress. Mutation of either rrpA or rrpB reduces catalase (KatA expression. However a rrpAB double mutant exhibits higher levels of resistance to hydrogen peroxide oxidative stress, with levels of KatA expression similar to the wild-type strain. Neither the rrpA nor rrpB mutant exhibits any significant difference in sensitivity to either cumene hydroperoxide or menadione oxidative stresses, but both mutants exhibit a reduced ability to survive aerobic (O2 stress, enhanced biofilm formation and reduced virulence in the Galleria mellonella infection model. The rrpAB double mutant exhibits wild-type levels of biofilm formation and wild-type levels of virulence in the Galleria mellonella infection model. Together these data indicate a role for both RrpA and RrpB in the C. jejuni peroxide oxidative and aerobic (O2 stress responses, enhancing bacterial survival in vivo and in the environment.

  11. Stability of UV exposed RR-P3BT films by spectroscopic ellipsometry

    International Nuclear Information System (INIS)

    Diware, Mangesh S.; Byun, J. S.; Hwang, S. Y.; Kim, T. J.; Kim, Y. D.

    2013-01-01

    Stability of regioregular poly(3-butylthiophene) (RR-P3BT) films under irradiation of ultra-violet (UV) light has been studied by spectroscopic ellipsometry at room temperature. Consistent decrease in dielectric function with UV exposure time showed the degree of degradation of polymer. This work suggests that, protective methods are mandatory to use this kind of material in optical devices.

  12. Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

    Directory of Open Access Journals (Sweden)

    Nigel P S Crawford

    2007-11-01

    Full Text Available A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b, was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.

  13. Role of acetyl-phosphate in activation of the Rrp2-RpoN-RpoS pathway in Borrelia burgdorferi.

    Directory of Open Access Journals (Sweden)

    Haijun Xu

    2010-09-01

    Full Text Available Borrelia burgdorferi, the Lyme disease spirochete, dramatically alters its transcriptome and proteome as it cycles between the arthropod vector and mammalian host. During this enzootic cycle, a novel regulatory network, the Rrp2-RpoN-RpoS pathway (also known as the σ(54-σ(S sigma factor cascade, plays a central role in modulating the differential expression of more than 10% of all B. burgdorferi genes, including the major virulence genes ospA and ospC. However, the mechanism(s by which the upstream activator and response regulator Rrp2 is activated remains unclear. Here, we show that none of the histidine kinases present in the B. burgdorferi genome are required for the activation of Rrp2. Instead, we present biochemical and genetic evidence that supports the hypothesis that activation of the Rrp2-RpoN-RpoS pathway occurs via the small, high-energy, phosphoryl-donor acetyl phosphate (acetyl∼P, the intermediate of the Ack-Pta (acetate kinase-phosphate acetyltransferase pathway that converts acetate to acetyl-CoA. Supplementation of the growth medium with acetate induced activation of the Rrp2-RpoN-RpoS pathway in a dose-dependent manner. Conversely, the overexpression of Pta virtually abolished acetate-induced activation of this pathway, suggesting that acetate works through acetyl∼P. Overexpression of Pta also greatly inhibited temperature and cell density-induced activation of RpoS and OspC, suggesting that these environmental cues affect the Rrp2-RpoN-RpoS pathway by influencing acetyl∼P. Finally, overexpression of Pta partially reduced infectivity of B. burgdorferi in mice. Taken together, these findings suggest that acetyl∼P is one of the key activating molecule for the activation of the Rrp2-RpoN-RpoS pathway and support the emerging concept that acetyl∼P can serve as a global signal in bacterial pathogenesis.

  14. The 10-item Remembered Relationship with Parents (RRP10) scale: two-factor model and association with adult depressive symptoms.

    Science.gov (United States)

    Denollet, Johan; Smolderen, Kim G E; van den Broek, Krista C; Pedersen, Susanne S

    2007-06-01

    Dysfunctional parenting styles are associated with poor mental and physical health. The 10-item Remembered Relationship with Parents (RRP(10)) scale retrospectively assesses Alienation (dysfunctional communication and intimacy) and Control (overprotection by parents), with an emphasis on deficiencies in empathic parenting. We examined the 2-factor structure of the RRP(10) and its relationship with adult depression. 664 respondents from the general population (48% men, mean age 54.6+/-14.2 years) completed the RRP(10), Parental Bonding Instrument (PBI), and Beck Depression Inventory. The Alienation and Control dimensions of the RRP(10) displayed a sound factor structure, good internal consistency (Cronbach's alpha=0.83-0.86), and convergent validity against the PBI scales. No significant gender differences were found on the RRP(10) scales. Stratifying by RRP(10) dimensions showed that respondents high in Alienation and Control, for both father (33.3% vs. 14.5%, pparental Alienation and Control. High Alienation and Control were independently related to increased risk of depressive symptoms. Given the brevity of the RRP(10), it can easily be used in epidemiological/clinical research on the link between the remembered relationship with parents and mental/physical health.

  15. Integration of HPV6 and downregulation of AKR1C3 expression mark malignant transformation in a patient with juvenile-onset laryngeal papillomatosis.

    Directory of Open Access Journals (Sweden)

    Christian Ulrich Huebbers

    Full Text Available Juvenile-onset recurrent respiratory papillomatosis (RRP is associated with low risk human papillomavirus (HPV types 6 and 11. Malignant transformation has been reported solely for HPV11-associated RRP in 2-4% of all RRP-cases, but not for HPV6. The molecular mechanisms in the carcinogenesis of low risk HPV-associated cancers are to date unknown. We report of a female patient, who presented with a laryngeal carcinoma at the age of 24 years. She had a history of juvenile-onset RRP with an onset at the age of three and subsequently several hundred surgical interventions due to multiple recurrences of RRP. Polymerase chain reaction (PCR or bead-based hybridization followed by direct sequencing identified HPV6 in tissue sections of previous papilloma and the carcinoma. P16(INK4A, p53 and pRb immunostainings were negative in all lesions. HPV6 specific fluorescence in situ hybridization (FISH revealed nuclear staining suggesting episomal virus in the papilloma and a single integration site in the carcinoma. Integration-specific amplification of papillomavirus oncogene transcripts PCR (APOT-PCR showed integration in the aldo-keto reductase 1C3 gene (AKR1C3 on chromosome 10p15.1. ArrayCGH detected loss of the other gene copy as part of a deletion at 10p14-p15.2. Western blot analysis and immunohistochemistry of the protein AKR1C3 showed a marked reduction of its expression in the carcinoma. In conclusion, we identified a novel molecular mechanism underlying a first case of HPV6-associated laryngeal carcinoma in juvenile-onset RRP, i.e. that HPV6 integration in the AKR1C3 gene resulted in loss of its expression. Alterations of AKR1C gene expression have previously been implicated in the tumorigenesis of other (HPV-related malignancies.

  16. The 10-item Remembered Relationship with Parents (RRP10) scale

    DEFF Research Database (Denmark)

    Denollet, Johan; Smolderen, Kim G E; van den Broek, Krista C

    2007-01-01

    Dysfunctional parenting styles are associated with poor mental and physical health. The 10-item Remembered Relationship with Parents (RRP(10)) scale retrospectively assesses Alienation (dysfunctional communication and intimacy) and Control (overprotection by parents), with an emphasis...... on deficiencies in empathic parenting. We examined the 2-factor structure of the RRP(10) and its relationship with adult depression....

  17. The Campylobacter jejuni Oxidative Stress Regulator RrpB Is Associated with a Genomic Hypervariable Region and Altered Oxidative Stress Resistance.

    Science.gov (United States)

    Gundogdu, Ozan; da Silva, Daiani T; Mohammad, Banaz; Elmi, Abdi; Wren, Brendan W; van Vliet, Arnoud H M; Dorrell, Nick

    2016-01-01

    Campylobacter jejuni is the leading cause of bacterial foodborne diarrhoeal disease worldwide. Despite the microaerophilic nature of the bacterium, C. jejuni can survive the atmospheric oxygen conditions in the environment. Bacteria that can survive either within a host or in the environment like C. jejuni require variable responses to survive the stresses associated with exposure to different levels of reactive oxygen species. The MarR-type transcriptional regulators RrpA and RrpB have recently been shown to play a role in controlling both the C. jejuni oxidative and aerobic stress responses. Analysis of 3,746 C. jejuni and 486 C. coli genome sequences showed that whilst rrpA is present in over 99% of C. jejuni strains, the presence of rrpB is restricted and appears to correlate with specific MLST clonal complexes (predominantly ST-21 and ST-61). C. coli strains in contrast lack both rrpA and rrpB . In C. jejuni rrpB + strains, the rrpB gene is located within a variable genomic region containing the IF subtype of the type I Restriction-Modification ( hsd ) system, whilst this variable genomic region in C. jejuni rrpB - strains contains the IAB subtype hsd system and not the rrpB gene. C. jejuni rrpB - strains exhibit greater resistance to peroxide and aerobic stress than C. jejuni rrpB + strains. Inactivation of rrpA resulted in increased sensitivity to peroxide stress in rrpB + strains, but not in rrpB - strains. Mutation of rrpA resulted in reduced killing of Galleria mellonella larvae and enhanced biofilm formation independent of rrpB status. The oxidative and aerobic stress responses of rrpB - and rrpB + strains suggest adaptation of C. jejuni within different hosts and niches that can be linked to specific MLST clonal complexes.

  18. Vessel calibration for accurate material accountancy at RRP

    International Nuclear Information System (INIS)

    Yanagisawa, Yuu; Ono, Sawako; Iwamoto, Tomonori

    2004-01-01

    RRP has a 800t·Upr capacity a year to re-process, where would be handled a large amount of nuclear materials as solution. A large scale plant like RRP will require accurate materials accountancy system, so that the vessel calibration with high-precision is very important as initial vessel calibration before operation. In order to obtain the calibration curve, it is needed well-known each the increment volume related with liquid height. Then we performed at least 2 or 3 times run with water for vessel calibration and careful evaluation for the calibration data should be needed. We performed vessel calibration overall 210 vessels, and the calibration of 81 vessels including IAT and OAT were held under presence of JSGO and IAEA inspectors taking into account importance on the material accountancy. This paper describes outline of the initial vessel calibration and calibration results based on back pressure measurement with dip tubes. (author)

  19. Designing and Operating for Safeguards: Lessons Learned From the Rokkasho Reprocessing Plant (RRP)

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Shirley J.; Ehinger, Michael

    2010-08-07

    This paper will address the lessons learned during the implementation of International Atomic Energy Agency (IAEA) safeguards at the Rokkasho Reprocessing Plant (RRP) which are relevant to the issue of ‘safeguards by design’. However, those lessons are a result of a cumulative history of international safeguards experiences starting with the West Valley reprocessing plant in 1969, continuing with the Barnwell plant, and then with the implementation of international safeguards at WAK in Germany and TRP in Japan. The design and implementation of safeguards at RRP in Japan is the latest and most challenging that the IAEA has faced. This paper will discuss the work leading up to the development of a safeguards approach, the design and operating features that were introduced to improve or aid in implementing the safeguards approach, and the resulting recommendations for future facilities. It will provide an overview of how ‘safeguardability’ was introduced into RRP.

  20. Designing and Operating for Safeguards: Lessons Learned From the Rokkasho Reprocessing Plant (RRP)

    International Nuclear Information System (INIS)

    Johnson, Shirley J.; Ehinger, Michael

    2010-01-01

    This paper will address the lessons learned during the implementation of International Atomic Energy Agency (IAEA) safeguards at the Rokkasho Reprocessing Plant (RRP) which are relevant to the issue of 'safeguards by design'. However, those lessons are a result of a cumulative history of international safeguards experiences starting with the West Valley reprocessing plant in 1969, continuing with the Barnwell plant, and then with the implementation of international safeguards at WAK in Germany and TRP in Japan. The design and implementation of safeguards at RRP in Japan is the latest and most challenging that the IAEA has faced. This paper will discuss the work leading up to the development of a safeguards approach, the design and operating features that were introduced to improve or aid in implementing the safeguards approach, and the resulting recommendations for future facilities. It will provide an overview of how 'safeguardability' was introduced into RRP.

  1. Structures of two exonucleases involved in controlled RNA turnover in yeast

    DEFF Research Database (Denmark)

    Jonstrup, Anette Thyssen; Midtgaard, Søren Fuglsang; Van, Lan Bich

    divalent cations. The Pop2p structure reveals that the ability of this enzyme to degrade poly(A)/(U)/(C), but not poly(G) may be determined by structural hindrance of interaction with this specific nucleotide. In Rrp6p, mutations known to confer specific RNA degradation phenotypes in yeast nuclei can now...... rid of aberrant RNAs. Here we describe the structures of two 3'-5' exonucleases involved in controlled RNA decay in yeast, Pop2p and Rrp6p. Rrp6p is associated with the nuclear exosome where it participates in the degradation of improperly processed precursor mRNAs and trimming of stable RNAs [1]. Pop...

  2. Minimum Energy of a Prismatic Joint with out: Actuator: Application on RRP Robot

    OpenAIRE

    Tawiwat V.; Tosapolporn P.; Kedit J.

    2009-01-01

    This research proposes the state of art on how to control or find the trajectory paths of the RRP robot when the prismatic joint is malfunction. According to this situation, the minimum energy of the dynamic optimization is applied. The RRP robot or similar systems have been used in many areas such as fire fighter truck, laboratory equipment and military truck for example a rocket launcher. In order to keep on task that assigned, the trajectory paths must be computed. Here, the open loop cont...

  3. The RRP Project: investigating radionuclide retardation in the host rock

    International Nuclear Information System (INIS)

    Alexander, W.R.; Frieg, B.; Ota, K.; Bossart, P.

    1996-01-01

    The Radionuclide Retardation Project (RRP), which is a joint Nagra/PNC (Power Reactor and Nuclear Fuel Development Corp.) project, has two components: the first (the Excavation Project, EP) looks at the behaviour of radionuclides which are so strongly retarded in the experimental shear zone that they cannot pass through the zones in experimentally reasonable times. In order to determine where radionuclide retardation has occurred in the pore space, as well as the flowpath geometry in the shear zone, the entire injection zone has to be excavated and taken back to the laboratory for analysis of the sites of retardation of the radionuclides. This approach has the advantage of allowing a detailed 3D description of the experimental shear zone. The aim of the second component of the project (Connected Porosities, CP) is to examine the fate of those radionuclides which diffuse out of the main water-conducting features in the shear zone and into the pore spaces of the rock matrix, where they become trapped. This represents a potentially significant retardation mechanism in a repository host rock. (author) 8 figs., refs

  4. Development and test of Nb3Sn cos-theta magnets based on RRp and PIT strands

    International Nuclear Information System (INIS)

    Feher, S.; Ambrosio, G.; Andreev, N.; Barzi, E.; Bordini, B.; Bossert, R.; Carcagno, R.; Kashikhin, V.S.; Kashikhin, V.V.; Lamm, M.J.; Novitski, I.; Pischalnikov, Yu.; Sylvester, C.; Tartaglia, M.; Turrioni, D.; Yamada, R.; Zlobin, A.V.; Fermilab

    2005-01-01

    As part of the High Field Magnet program at Fermilab three cos(Θ) magnets--two mirror dipole magnets utilizing RRP cable and one dipole magnet utilizing PIT cable--have been designed, fabricated and tested recently. Both mirror magnets with RRP strands only reached ∼50-60% of their estimated critical current limit. The PIT conductor based dipole however reached its critical current limit producing over 10 T magnetic field in the bore of the magnet. This paper describes the parameters of superconducting strands and cable, the details of magnet design and fabrication procedure, and reports the results

  5. Development and test of Nb3Sn cos-theta magnets based on RRP and PIT strands

    Energy Technology Data Exchange (ETDEWEB)

    Feher, S.; Ambrosio, G.; Andreev, N.; Barzi, E.; Bordini, B.; Bossert, R.; Carcagno, R.; Kashikhin, V.S.; Kashikhin, V.V.; Lamm, M.J.; Novitski, I.; Pischalnikov, Yu.; Sylvester, C.; Tartaglia, M.; Turrioni, D.; Yamada, R.; Zlobin, A.V.; /Fermilab

    2005-09-01

    As part of the High Field Magnet program at Fermilab three cos({theta}) magnets--two mirror dipole magnets utilizing RRP cable and one dipole magnet utilizing PIT cable--have been designed, fabricated and tested recently. Both mirror magnets with RRP strands only reached {approx}50-60% of their estimated critical current limit. The PIT conductor based dipole however reached its critical current limit producing over 10 T magnetic field in the bore of the magnet. This paper describes the parameters of superconducting strands and cable, the details of magnet design and fabrication procedure, and reports the results.

  6. Rrp12 and the Exportin Crm1 participate in late assembly events in the nucleolus during 40S ribosomal subunit biogenesis.

    Science.gov (United States)

    Moriggi, Giulia; Nieto, Blanca; Dosil, Mercedes

    2014-12-01

    During the biogenesis of small ribosomal subunits in eukaryotes, the pre-40S particles formed in the nucleolus are rapidly transported to the cytoplasm. The mechanisms underlying the nuclear export of these particles and its coordination with other biogenesis steps are mostly unknown. Here we show that yeast Rrp12 is required for the exit of pre-40S particles to the cytoplasm and for proper maturation dynamics of upstream 90S pre-ribosomes. Due to this, in vivo elimination of Rrp12 leads to an accumulation of nucleoplasmic 90S to pre-40S transitional particles, abnormal 35S pre-rRNA processing, delayed elimination of processing byproducts, and no export of intermediate pre-40S complexes. The exportin Crm1 is also required for the same pre-ribosome maturation events that involve Rrp12. Thus, in addition to their implication in nuclear export, Rrp12 and Crm1 participate in earlier biosynthetic steps that take place in the nucleolus. Our results indicate that, in the 40S subunit synthesis pathway, the completion of early pre-40S particle assembly, the initiation of byproduct degradation and the priming for nuclear export occur in an integrated manner in late 90S pre-ribosomes.

  7. Avaliando lembranças de alienação e controle parental: evidências de validade de construto da RRP10 no Brasil

    Directory of Open Access Journals (Sweden)

    Rildésia S. V. Gouveia

    2013-01-01

    Full Text Available O presente estudo objetivou adaptar para o contexto brasileiro a Escala de Lembranças do Relacionamento com os Pais (RRP10 - 10-Item Remembered Relationship with Parents, conhecendo evidências de seus parâmetros psicométricos. Participaram 298 estudantes universitários de uma instituição privada de João Pessoa (PB, a maioria do sexo feminino (55,6% e idade média de 19 anos. Estes responderam quatro medidas, entre elas a RRP10 e perguntas demográficas. Os resultados confirmaram a estrutura bifatorial teorizada, cujos fatores (alienação e controle apresentaram evidências de precisão (confiabilidade composta e consistência interna e validade convergente-discriminante. Concluiu-se que esta medida poderá ser empregada adequadamente no futuro, uma vez que reuniu evidências de validade de construto.

  8. Occupational dose at Rokkasho reprocessing plant (RRP)

    International Nuclear Information System (INIS)

    Takashima, F.; Taguchi, R.; Kano, M.; Moriyama, T.; Ogaki, K.; Noda, K.

    2008-01-01

    In Japan, Rokkasho Reprocessing Plant (RRP) is going to start the operation in service as the first large-scale commercial reprocessing plant of spent fuels that has annual reprocessing quantity of 800tU pr in maximum. The occupational external exposure is controlled for the purpose of keeping dose as low as reasonably achievable, and it is monitored by the personal dosimeter. On the other hand, the occupational internal exposure is controlled for the purpose of preventing, and it is monitored by the periodical evaluation of internal dose from the radioactive concentration in air of workplace. The individual doses of radiation workers are less than the dose limits in the statute and our lower management values enough. Dose data will be stored continuously and the rational management method will be examined. (author)

  9. Health-related quality of life using SF-8 and EPIC questionnaires after treatment with radical retropubic prostatectomy and permanent prostate brachytherapy

    International Nuclear Information System (INIS)

    Hashine, Katsuyoshi; Kusuhara, Yoshito; Miura, Noriyoshi; Shirato, Akitomi; Sumiyoshi, Yoshiteru; Kataoka, Masaaki

    2009-01-01

    The health-related quality of life (HRQOL) after treatment of prostate cancer is examined using a new HRQOL tool. HRQOL, based on the expanded prostate cancer index composite (EPIC) and SF-8 questionnaires, was prospectively compared after either a radical retropubic prostatectomy (RRP) or a permanent prostate brachytherapy (PPB) at a single institute. Between October 2005 and June 2007, 96 patients were treated by an RRP and 88 patients were treated by a PPB. A HRQOL survey was completed at baseline, and at 1, 3, 6 and 12 months after treatment, prospectively. The general HRQOL in the RRP and PPB groups was not different after 3 months. However, at baseline and 1 month after treatment, the mental component summary was significantly better in the PPB group than in the RRP group. Moreover, the disease-specific HRQOL was worse regarding urinary and sexual functions in the RRP group. Urinary irritative/obstructive was worse in the PPB group, but urinary incontinence was worse in the RRP group and had not recovered to baseline after 12 months. The bowel function and bother were worse in the PPB group than in the RRP group after 3 months. In the RRP group, the patients with nerve sparing demonstrated the same scores in sexual function as the PPB group. This prospective study revealed the differences in the HRQOL after an RRP and PPB. Disease-specific HRQOL is clarified by using EPIC survey. These results will be helpful for making treatment decisions. (author)

  10. Performance of Nb3Sn RRP strands and cables based on a 108/127 stack design

    International Nuclear Information System (INIS)

    Barzi, E.; Ambrosio, G.; Andreev, N.; Bossert, R.; Carcagno, R.; Feher, S.; Kashikhin, V.S.; Kashikhin, V.V.; Lamm, M.J.; Nobrega, F.; Novitski, I.; Pishalnikov, Y.; Sylvester, C.; Tartaglia, M.; Turrioni, D.; Yamada, R.; Zlobin, A.V.; Field, M.; Hong, S.; Parrell, J.; Zhang, Y.

    2006-01-01

    The high performance Nb 3 Sn strand produced by Oxford Superconducting Technology (OST) with the Restack Rod Process (RRP) is presently considered as a baseline conductor for the Fermilab's accelerator magnet R and D program. To improve the strand stability in the current and field range expected in magnet models, the number of subelements in the strand was increased by a factor of two (from 54 to 108), which resulted in a smaller effective filament size. The performance of the 1.0 and 0.7 mm strands of this design was studied using virgin and deformed strand samples. 27-strand Rutherford cables made of 1 mm strand were also tested using a superconducting transformer, small racetrack and 1-m shell-type dipole coils. This paper presents the RRP strand and cable parameters, and reports the results of strand, cable and coil testing

  11. Performance of Nb3Sn RRP strands and cables based on a 108/127 stack design

    Energy Technology Data Exchange (ETDEWEB)

    Barzi, E.; Ambrosio, G.; Andreev, N.; Bossert, R.; Carcagno, R.; Feher, S.; Kashikhin, V.S.; Kashikhin, V.V.; Lamm, M.J.; Nobrega, F.; Novitski, I.; /Fermilab /Oxford Supercond. Tech., Carteret

    2006-08-01

    The high performance Nb{sub 3}Sn strand produced by Oxford Superconducting Technology (OST) with the Restack Rod Process (RRP) is presently considered as a baseline conductor for the Fermilab's accelerator magnet R&D program. To improve the strand stability in the current and field range expected in magnet models, the number of subelements in the strand was increased by a factor of two (from 54 to 108), which resulted in a smaller effective filament size. The performance of the 1.0 and 0.7 mm strands of this design was studied using virgin and deformed strand samples. 27-strand Rutherford cables made of 1 mm strand were also tested using a superconducting transformer, small racetrack and 1-m shell-type dipole coils. This paper presents the RRP strand and cable parameters, and reports the results of strand, cable and coil testing.

  12. Clinical and biochemical outcomes of men undergoing radical prostatectomy or radiation therapy for localized prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schreiber, David; Weiss, Jeffrey P.; Safdieh, Joseph; Weiner, Joseph; Rotman, Marvin; Schwartz, David [Veterans Affairs, New York Harbor Healthcare System, Brooklyn (United States); Rineer, Justin [University of Florida Health Cancer Center at Orlando Health, Orlando (United States)

    2015-03-15

    We analyzed outcomes of patients with prostate cancer undergoing either radical retropubic prostatectomy (RRP) +/- salvage radiation or definitive radiation therapy (RT) +/- androgen deprivation. From 2003-2010 there were 251 patients who underwent RRP and 469 patients who received RT (> or =7,560 cGy) for prostate cancer. Kaplan-Meier analysis was performed with the log-rank test to compare biochemical control (bCR), distant metastatic-free survival (DMPFS), and prostate cancer-specific survival (PCSS) between the two groups. The median follow-up was 70 months and 61.3% of the men were African American. For low risk disease the 6-year bCR were 90.3% for RT and 85.6% for RRP (p = 0.23) and the 6-year post-salvage bCR were 90.3% vs. 90.9%, respectively (p = 0.84). For intermediate risk disease the 6-year bCR were 82.6% for RT and 59.7% for RRP (p < 0.001) and 82.6% vs. 74.0%, respectively, after including those salvaged with RT (p = 0.06). For high risk disease, the 6-year bCR were 67.4% for RT and 41.3% for RRP (p < 0.001) and after including those salvaged with RT was 67.4% vs. 43.1%, respectively (p < 0.001). However, there were no significant differences between the two groups in regards to DMPFS or PCSS. Treatment approaches utilizing RRP +/- salvage radiation or RT +/- androgen deprivation yielded equivalent DMPFS and PCSS outcomes. Biochemical control rates, using their respective definitions, appeared equivalent or better in those who received treatment with RT.

  13. Clinical and biochemical outcomes of men undergoing radical prostatectomy or radiation therapy for localized prostate cancer

    International Nuclear Information System (INIS)

    Schreiber, David; Weiss, Jeffrey P.; Safdieh, Joseph; Weiner, Joseph; Rotman, Marvin; Schwartz, David; Rineer, Justin

    2015-01-01

    We analyzed outcomes of patients with prostate cancer undergoing either radical retropubic prostatectomy (RRP) +/- salvage radiation or definitive radiation therapy (RT) +/- androgen deprivation. From 2003-2010 there were 251 patients who underwent RRP and 469 patients who received RT (> or =7,560 cGy) for prostate cancer. Kaplan-Meier analysis was performed with the log-rank test to compare biochemical control (bCR), distant metastatic-free survival (DMPFS), and prostate cancer-specific survival (PCSS) between the two groups. The median follow-up was 70 months and 61.3% of the men were African American. For low risk disease the 6-year bCR were 90.3% for RT and 85.6% for RRP (p = 0.23) and the 6-year post-salvage bCR were 90.3% vs. 90.9%, respectively (p = 0.84). For intermediate risk disease the 6-year bCR were 82.6% for RT and 59.7% for RRP (p < 0.001) and 82.6% vs. 74.0%, respectively, after including those salvaged with RT (p = 0.06). For high risk disease, the 6-year bCR were 67.4% for RT and 41.3% for RRP (p < 0.001) and after including those salvaged with RT was 67.4% vs. 43.1%, respectively (p < 0.001). However, there were no significant differences between the two groups in regards to DMPFS or PCSS. Treatment approaches utilizing RRP +/- salvage radiation or RT +/- androgen deprivation yielded equivalent DMPFS and PCSS outcomes. Biochemical control rates, using their respective definitions, appeared equivalent or better in those who received treatment with RT.

  14. Is there any change in pelvic floor electromyography during the first 6 months after radical retropubic prostatectomy?

    Science.gov (United States)

    Hacad, Claudia R; Glazer, Howard I; Zambon, João Paulo C; Burti, Juliana S; Almeida, Fernando G

    2015-03-01

    The aim of this study is to determine electromyographic pelvic floor muscles activity during the first 6 months post RRP and its relationship to urinary continence. Thirty-eight men (mean age of 63.1 ± 5.7 year) with prostate cancer scheduled for open radical retropubic prostatectomy were evaluated. pelvic radiotherapy, systemic or neurologic diseases, pre-operative International Prostate Symptoms Score (IPSS) >7 and OABq ≥8. Surface electromyography (sEMG) evaluation, IPSS, Urinary Distress Inventory, Incontinence Impact Questionnaire, and Overactive Bladder Questionnaire-short form were applied before and at 1, 3, and 6 months after RRP. Six months after surgery, 18 men (47.4 %) presented urinary leakage. The sEMG evaluations within the first 6 months presented changes in fast contraction amplitude (p = 0.006), rest amplitude after fast contraction (p = 0.04), 10 s sustained contraction mean amplitude (p = 0.024) and final rest amplitude (p = 0.011). We observed that continent and incontinent patients as a group presented electromyographic changes during the first 6 months after radical prostatectomy that could be justified by the denervation/reinnervation of the external urethral sphincter. This finding is consistent with the adaptation of the pelvic floor musculature to the new urethral sphincter condition following surgery.

  15. Oncolytic Herpes Virus rRp450 Shows Efficacy in Orthotopic Xenograft Group 3/4 Medulloblastomas and Atypical Teratoid/Rhabdoid Tumors

    Directory of Open Access Journals (Sweden)

    Adam W. Studebaker

    2017-09-01

    Full Text Available Pediatric brain tumors including medulloblastoma and atypical teratoid/rhabdoid tumor are associated with significant mortality and treatment-associated morbidity. While medulloblastoma tumors within molecular subgroups 3 and 4 have a propensity to metastasize, atypical teratoid/rhabdoid tumors frequently afflict a very young patient population. Adjuvant treatment options for children suffering with these tumors are not only sub-optimal but also associated with many neurocognitive obstacles. A potentially novel treatment approach is oncolytic virotherapy, a developing therapeutic platform currently in early-phase clinical trials for pediatric brain tumors and recently US Food and Drug Administration (FDA-approved to treat melanoma in adults. We evaluated the therapeutic potential of the clinically available oncolytic herpes simplex vector rRp450 in cell lines derived from medulloblastoma and atypical teratoid/rhabdoid tumor. Cells of both tumor types were supportive of virus replication and virus-mediated cytotoxicity. Orthotopic xenograft models of medulloblastoma and atypical teratoid/rhabdoid tumors displayed significantly prolonged survival following a single, stereotactic intratumoral injection of rRp450. Furthermore, addition of the chemotherapeutic prodrug cyclophosphamide (CPA enhanced rRp450’s in vivo efficacy. In conclusion, oncolytic herpes viruses with the ability to bioactivate the prodrug CPA within the tumor microenvironment warrant further investigation as a potential therapy for pediatric brain tumors.

  16. The Safeguards analysis applied to the RRP. Automatic sampling authentication system

    International Nuclear Information System (INIS)

    Ono, Sawako; Nakashima, Shinichi; Iwamoto, Tomonori

    2004-01-01

    The sampling for analysis from vessels and columns at the Rokkasho Reprocessing Plant (RRP) is performed mostly by the automatic sampling system. The safeguards sample for the verification also will be taken using these sampling systems and transfer to the OSL though the pneumatic transfer network owned and controlled by operator. In order to maintaining sample integrity and continuity of knowledge (CoK) for throughout the sample processing. It is essential to develop and establish the authentication measures for the automatic sampling system including transfer network. We have developed the Automatic Sampling Authentication System (ASAS) under consultation by IAEA. This paper describes structure, function and concept of ASAS. (author)

  17. RRP Nb3Sn strand studies for LARP

    International Nuclear Information System (INIS)

    Barzi, Emanuela; Bossert, Rodger; Caspi, Shlomo; Dietderich, Daniel R.; Ferracin, Paolo; Ghosh, Arup; Turrioni, Daniele

    2006-01-01

    The Nb 3 Sn strand chosen for the next step in the magnet R and D of the U.S. LHC Accelerator Research Program is the 54/61 sub-element Restacked Rod Process by Oxford Instruments, Superconducting Technology. To ensure that the 0.7 mm RRP strands to be used in the upcoming LARP magnets are suitable, extensive studies were performed. Measurements included the critical current, e , using the voltage-current (V-I) method, the stability current, I S , as the minimal quench current obtained with the voltage-field (V-H) method, and RRR. Magnetization was measured at low and high fields to determine the effective filament size and to detect flux jumps. Effects of heat treatment temperature and durations on I e and I S were also studied. Using strand billet qualification and tests of strands extracted from cables, the short sample limits of magnet performance were obtained. The details and the results of this investigation are herein described

  18. RRP Nb3Sn Strand Studies for LARP

    International Nuclear Information System (INIS)

    Barzi, Emanuela; Bossert, Rodger; Caspi, Shlomo; Dietderich, Daniel R.; Ferracin, Paolo; Ghosh, Arup; Turrioni, Daniele

    2007-01-01

    The Nb 3 Sn strand chosen for the next step in the magnet R and D of the U.S. LHC Accelerator Research Program is the 54/61 sub-element Restacked Rod Process by Oxford Instruments, Superconducting Technology. To ensure that the 0.7 mm RRP strands to be used in the upcoming LARP magnets are suitable, extensive studies were performed. Measurements included the critical current, I c , using the voltage-current (V-I) method, the stability current, I S , as the minimal quench current obtained with the voltage-field (V-H) method, and RRR. Magnetization was measured at low and high fields to determine the effective filament size and to detect flux jumps. Effects of heat treatment temperature and durations on I c and I S were also studied. Using strand billet qualification and tests of strands extracted from cables, the short sample limits of magnet performance were obtained. The details and the results of this investigation are herein described

  19. Crystallization and preliminary X-ray diffraction analysis of the P3 RNA domain of yeast ribonuclease MRP in a complex with RNase P/MRP protein components Pop6 and Pop7

    International Nuclear Information System (INIS)

    Perederina, Anna; Esakova, Olga; Quan, Chao; Khanova, Elena; Krasilnikov, Andrey S.

    2009-01-01

    This article describes the first successful crystallization of components of eukaryotic ribonucleases P/MRP. Yeast RNase MRP RNA domain P3 was crystallized in a complex with the proteins Pop6 and Pop7; the crystals diffracted to 3.25 Å resolution. Eukaryotic ribonucleases P and MRP are closely related RNA-based enzymes which contain a catalytic RNA component and several protein subunits. The roles of the protein subunits in the structure and function of eukaryotic ribonucleases P and MRP are not clear. Crystals of a complex that included a circularly permuted 46-nucleotide-long P3 domain of the RNA component of Saccharomyces cerevisiae ribonuclease MRP and selenomethionine derivatives of the shared ribonuclease P/MRP protein components Pop6 (18.2 kDa) and Pop7 (15.8 kDa) were obtained using the sitting-drop vapour-diffusion method. The crystals belonged to space group P4 2 22 (unit-cell parameters a = b = 127.2, c = 76.8 Å, α = β = γ = 90°) and diffracted to 3.25 Å resolution

  20. Charge Carrier Transport and Photogeneration in P3HT:PCBM Photovoltaic Blends

    KAUST Repository

    Laquai, Frederic

    2015-05-03

    This article reviews the charge transport and photogeneration in bulk-heterojunction solar cells made from blend films of regioregular poly(3-hexylthiophene) (RR-P3HT) and methano­fullerene (PCBM). The charge transport, specifically the hole mobility in the RR-P3HT phase of the polymer:fullerene photovoltaic blend, is dramatically affected by thermal annealing. The hole mobility increases more than three orders of magnitude and reaches a value of up to 2 × 10−4 cm2 V−1 s−1 after the thermal annealing process as a result of an improved semi-crystallinity of the film. This significant increase of the hole mobility balances the electron and hole mobilities in a photovoltaic blend in turn reducing space-charge formation, and this is the most important factor for the strong enhancement of the photovoltaic efficiency compared to an as cast, that is, non-annealed device. In fact, the balanced charge carrier mobility in RR-P3HT:PCBM blends in combination with a field- and temperature-independent charge carrier generation and greatly reduced non-geminate recombination explains the large quantum efficiencies mea­sured in P3HT:PCBM photovoltaic devices.

  1. The Visual Analogue Scale for Rating, Ranking and Paired-Comparison (VAS-RRP): A new technique for psychological measurement.

    Science.gov (United States)

    Sung, Yao-Ting; Wu, Jeng-Shin

    2018-04-17

    Traditionally, the visual analogue scale (VAS) has been proposed to overcome the limitations of ordinal measures from Likert-type scales. However, the function of VASs to overcome the limitations of response styles to Likert-type scales has not yet been addressed. Previous research using ranking and paired comparisons to compensate for the response styles of Likert-type scales has suffered from limitations, such as that the total score of ipsative measures is a constant that cannot be analyzed by means of many common statistical techniques. In this study we propose a new scale, called the Visual Analogue Scale for Rating, Ranking, and Paired-Comparison (VAS-RRP), which can be used to collect rating, ranking, and paired-comparison data simultaneously, while avoiding the limitations of each of these data collection methods. The characteristics, use, and analytic method of VAS-RRPs, as well as how they overcome the disadvantages of Likert-type scales, ranking, and VASs, are discussed. On the basis of analyses of simulated and empirical data, this study showed that VAS-RRPs improved reliability, response style bias, and parameter recovery. Finally, we have also designed a VAS-RRP Generator for researchers' construction and administration of their own VAS-RRPs.

  2. Development and test of Nb3sn cos-theta coils made of high-jc rrp strands

    Energy Technology Data Exchange (ETDEWEB)

    Bossert, R.; Ambrosio, G.; Andreev, N.; Barzi, E.; Carcagno, R.; Feher, S.; Kashikhin, V.S.; Kashikhin, V.V.; Lamm, M.J.; Novitski, I.; Pischalnikov, Yu.; Sylvester, C.; Tartaglia, M.; Turrioni, D.; Yamada, R.; Zlobin, A.V.; /Fermilab

    2005-10-01

    A series of 1-m long Nb3Sn dipole magnets have been built at Fermilab in an attempt to refine the wind-and-react technology for Nb{sub 3}Sn conductor. Models have been made with MJR and PIT strand with varying degrees of success. Subsequently two new dipole ''mirror'' magnets based on RRP Nb{sub 3}Sn coils were constructed and tested. This paper describes the design, fabrication and test results of those magnets.

  3. Charge carrier transport and photogeneration in P3HT:PCBM photovoltaic blends.

    Science.gov (United States)

    Laquai, Frédéric; Andrienko, Denis; Mauer, Ralf; Blom, Paul W M

    2015-06-01

    This article reviews the charge transport and photogeneration in bulk-heterojunction solar cells made from blend films of regioregular poly(3-hexylthiophene) (RR-P3HT) and methano-fullerene (PCBM). The charge transport, specifically the hole mobility in the RR-P3HT phase of the polymer:fullerene photovoltaic blend, is dramatically affected by thermal annealing. The hole mobility increases more than three orders of magnitude and reaches a value of up to 2 × 10(-4) cm(2) V(-1) s(-1) after the thermal annealing process as a result of an improved semi-crystallinity of the film. This significant increase of the hole mobility balances the electron and hole mobilities in a photovoltaic blend in turn reducing space-charge formation, and this is the most important factor for the strong enhancement of the photovoltaic efficiency compared to an as cast, that is, non-annealed device. In fact, the balanced charge carrier mobility in RR-P3HT:PCBM blends in combination with a field- and temperature-independent charge carrier generation and greatly reduced non-geminate recombination explains the large quantum efficiencies mea-sured in P3HT:PCBM photovoltaic devices. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Principal component analysis reveals gender-specific predictors of cardiometabolic risk in 6th graders

    Directory of Open Access Journals (Sweden)

    Peterson Mark D

    2012-11-01

    Full Text Available Abstract Background The purpose of this study was to determine the sex-specific pattern of pediatric cardiometabolic risk with principal component analysis, using several biological, behavioral and parental variables in a large cohort (n = 2866 of 6th grade students. Methods Cardiometabolic risk components included waist circumference, fasting glucose, blood pressure, plasma triglycerides levels and HDL-cholesterol. Principal components analysis was used to determine the pattern of risk clustering and to derive a continuous aggregate score (MetScore. Stratified risk components and MetScore were analyzed for association with age, body mass index (BMI, cardiorespiratory fitness (CRF, physical activity (PA, and parental factors. Results In both boys and girls, BMI and CRF were associated with multiple risk components, and overall MetScore. Maternal smoking was associated with multiple risk components in girls and boys, as well as MetScore in boys, even after controlling for children’s BMI. Paternal family history of early cardiovascular disease (CVD and parental age were associated with increased blood pressure and MetScore for girls. Children’s PA levels, maternal history of early CVD, and paternal BMI were also indicative for various risk components, but not MetScore. Conclusions Several biological and behavioral factors were independently associated with children’s cardiometabolic disease risk, and thus represent a unique gender-specific risk profile. These data serve to bolster the independent contribution of CRF, PA, and family-oriented healthy lifestyles for improving children’s health.

  5. Crystallization and preliminary X-ray diffraction analysis of the P3 RNA domain of yeast ribonuclease MRP in a complex with RNase P/MRP protein components Pop6 and Pop7.

    Science.gov (United States)

    Perederina, Anna; Esakova, Olga; Quan, Chao; Khanova, Elena; Krasilnikov, Andrey S

    2010-01-01

    Eukaryotic ribonucleases P and MRP are closely related RNA-based enzymes which contain a catalytic RNA component and several protein subunits. The roles of the protein subunits in the structure and function of eukaryotic ribonucleases P and MRP are not clear. Crystals of a complex that included a circularly permuted 46-nucleotide-long P3 domain of the RNA component of Saccharomyces cerevisiae ribonuclease MRP and selenomethionine derivatives of the shared ribonuclease P/MRP protein components Pop6 (18.2 kDa) and Pop7 (15.8 kDa) were obtained using the sitting-drop vapour-diffusion method. The crystals belonged to space group P4(2)22 (unit-cell parameters a = b = 127.2, c = 76.8 A, alpha = beta = gamma = 90 degrees ) and diffracted to 3.25 A resolution.

  6. Prospective longitudinal comparative study of health-related quality of life in patients treated with radical prostatectomy or permanent brachytherapy for prostate cancer

    International Nuclear Information System (INIS)

    Kobuke, Makoto; Saika, Takashi; Nakanishi, Yoshiko

    2009-01-01

    To determine health-related quality of life (HRQOL) after radical retropubic prostatectomy (RRP) or permanent prostate brachytherapy (BT), third party-conducted QOL surveys were prospectively compared. Between 2004 and 2005, 37 patients underwent RRP and 36 were treated with BT. A QOL survey consisting of the Medical Outcomes Study 36-Item Short Form (SF-36), the University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) and the International Prostate Symptoms Score (IPSS) was completed prospectively by a research coordinator at baseline, and at 1, 3, 6 and 12 months after treatment. The RRP patients scored well in general QOL except at 1 month after surgery, with their mental health better than at baseline by 6 months after surgery. Disease-specific QOL in RRP patients received a low score at 1 month for both urinary and sexual function, though urinary function rapidly recovered to baseline levels. BT patient QOL was not affected by the therapy except in the IPSS score. However, general and mental health scores in BT patients were inferior to those in RRP patients. This prospective study revealed differences in QOL after RRP and BT. These results will be helpful in making treatment decisions. (author)

  7. The adenovirus E4 11 k protein binds and relocalizes the cytoplasmic P-body component Ddx6 to aggresomes

    International Nuclear Information System (INIS)

    Greer, Amy E.; Hearing, Patrick; Ketner, Gary

    2011-01-01

    The adenovirus E4 11 k protein, product of E4 ORF3, is required in infection for processes including normal accumulation of viral late mRNAs. 11 k restructures both the nucleus and cytoplasm of infected cells by relocalizing specific host cell target proteins, most strikingly components of nuclear PML oncogenic domains. It is likely that in many cases relocalization inactivates target proteins to produce 11 k's effects, although the mechanism and targets for stimulation of late mRNA accumulation is unknown. We have identified a new set of proteins relocalized by 11 k: at least five protein components of cytoplasmic mRNA processing bodies (p-bodies) are found in 11 k-induced cytoplasmic aggresomes, sites where proteins are inactivated or destroyed. One of these p-body proteins, RNA helicase Ddx6, binds 11 k, suggesting a mechanism for relocalization. Because p-bodies are sites for mRNA degradation, their modification by 11 k may provide an explanation for the role of 11 k in viral late mRNA accumulation.

  8. Role of Nab2 in RNA metabolism in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Olszewski, Pawel

    RNP assembly generates errors, which are tracked down by nuclear surveillance mechanisms. Thus, not surprisingly, protein components of mRNPs have multiple functions in the biogenesis of the particle but also interact with the surveillance machinery. An example of such a multifunctional factor is the S......RNP components showed changes in the Nab2 interactome in the absence of Rrp6, and also suggested that Nab2 binds to multiple sites on the mRNA. Wide-range proteomic analysis of Nab2 immunoprecipitates revealed association with C/D box snoRNP components. These novel interactions were supported by the presence...

  9. Boudin trafficking reveals the dynamic internalisation of specific septate junction components in Drosophila.

    Science.gov (United States)

    Tempesta, Camille; Hijazi, Assia; Moussian, Bernard; Roch, Fernando

    2017-01-01

    The maintenance of paracellular barriers in invertebrate epithelia depends on the integrity of specific cell adhesion structures known as septate junctions (SJ). Multiple studies in Drosophila have revealed that these junctions have a stereotyped architecture resulting from the association in the lateral membrane of a large number of components. However, little is known about the dynamic organisation adopted by these multi-protein complexes in living tissues. We have used live imaging techniques to show that the Ly6 protein Boudin is a component of these adhesion junctions and can diffuse systemically to associate with the SJ of distant cells. We also observe that this protein and the claudin Kune-kune are endocytosed in epidermal cells during embryogenesis. Our data reveal that the SJ contain a set of components exhibiting a high membrane turnover, a feature that could contribute in a tissue-specific manner to the morphogenetic plasticity of these adhesion structures.

  10. Quench performance of Nb3Sn cos-theta coils made of 108/127 RRP strands

    International Nuclear Information System (INIS)

    Zlobin, A.V.; Ambrosio, G.; Andreev, N.; Barzi, E.; Bossert, R.; Carcagno, R.; Kashikhin, V.S.; Kashikhin, V.V.; Lamm, M.J.; Nobrega, F.; Novitski, I.

    2007-01-01

    A series of 1-m long Nb 3 Sn dipole models has been built at Fermilab in an attempt to refine the wind-and-react technology for Nb3Sn accelerator magnets. Three models made with Powder-in-Tube Nb 3 Sn strand reached their design field of 10 T demonstrating a good reproducibility of magnet quench performance and field quality. Recently a new dipole 'mirror' model based on Nb 3 Sn coil made of improved Restack Rod Process strand was constructed and tested reaching the maximum field above 11 T. This paper describes the parameters of the RRP strand and cable used as well as the design, fabrication and test results of this magnet

  11. Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Dai, Wei; Cheung, Arthur Kwok Leung; Ko, Josephine Mun Yee; Cheng, Yue; Zheng, Hong; Ngan, Roger Kai Cheong; Ng, Wai Tong; Lee, Anne Wing Mui; Yau, Chun Chung; Lee, Victor Ho Fu; Lung, Maria Li

    2015-01-01

    Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10 −9 ), but was less obvious in other types of solid tumors except for prostate and Epstein–Barr virus (EBV)-positive gastric cancer (FDR<10 −3 ). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection

  12. Exploring a minimal two-component p53 model

    International Nuclear Information System (INIS)

    Sun, Tingzhe; Zhu, Feng; Shen, Pingping; Yuan, Ruoshi; Xu, Wei

    2010-01-01

    The tumor suppressor p53 coordinates many attributes of cellular processes via interlocked feedback loops. To understand the biological implications of feedback loops in a p53 system, a two-component model which encompasses essential feedback loops was constructed and further explored. Diverse bifurcation properties, such as bistability and oscillation, emerge by manipulating the feedback strength. The p53-mediated MDM2 induction dictates the bifurcation patterns. We first identified irradiation dichotomy in p53 models and further proposed that bistability and oscillation can behave in a coordinated manner. Further sensitivity analysis revealed that p53 basal production and MDM2-mediated p53 degradation, which are central to cellular control, are most sensitive processes. Also, we identified that the much more significant variations in amplitude of p53 pulses observed in experiments can be derived from overall amplitude parameter sensitivity. The combined approach with bifurcation analysis, stochastic simulation and sampling-based sensitivity analysis not only gives crucial insights into the dynamics of the p53 system, but also creates a fertile ground for understanding the regulatory patterns of other biological networks

  13. Metallurgical evaluation of laser additive manufactured Ti6Al4V components

    CSIR Research Space (South Africa)

    Mutombo, K

    2013-10-01

    Full Text Available of contact between single deposited layer and Ti6Al4V base as well as the tensile properties of the component were evaluated. Powdered metal globularization, size segregation, un-melted or semi-melted particles and chemical surface contamination were revealed...

  14. Quench performance of Nb3Sn cos-theta coils made of 108/127 RRP strands

    Energy Technology Data Exchange (ETDEWEB)

    Zlobin, A.V.; Ambrosio, G.; Andreev, N.; Barzi, E.; Bossert, R.; Carcagno, R.; Kashikhin, V.S.; Kashikhin, V.V.; Lamm, M.J.; Nobrega, F.; Novitski, I.; /Fermilab

    2007-07-01

    A series of 1-m long Nb{sub 3}Sn dipole models has been built at Fermilab in an attempt to refine the wind-and-react technology for Nb3Sn accelerator magnets. Three models made with Powder-in-Tube Nb{sub 3}Sn strand reached their design field of 10 T demonstrating a good reproducibility of magnet quench performance and field quality. Recently a new dipole 'mirror' model based on Nb{sub 3}Sn coil made of improved Restack Rod Process strand was constructed and tested reaching the maximum field above 11 T. This paper describes the parameters of the RRP strand and cable used as well as the design, fabrication and test results of this magnet.

  15. Genetic rearrangements of six wheat-agropyron cristatum 6P addition lines revealed by molecular markers.

    Directory of Open Access Journals (Sweden)

    Haiming Han

    Full Text Available Agropyron cristatum (L. Gaertn. (2n = 4x = 28, PPPP not only is cultivated as pasture fodder but also could provide many desirable genes for wheat improvement. It is critical to obtain common wheat-A. cristatum alien disomic addition lines to locate the desired genes on the P genome chromosomes. Comparative analysis of the homoeologous relationships between the P genome chromosome and wheat genome chromosomes is a key step in transferring different desirable genes into common wheat and producing the desired alien translocation line while compensating for the loss of wheat chromatin. In this study, six common wheat-A. cristatum disomic addition lines were produced and analyzed by phenotypic examination, genomic in situ hybridization (GISH, SSR markers from the ABD genomes and STS markers from the P genome. Comparative maps, six in total, were generated and demonstrated that all six addition lines belonged to homoeologous group 6. However, chromosome 6P had undergone obvious rearrangements in different addition lines compared with the wheat chromosome, indicating that to obtain a genetic compensating alien translocation line, one should recombine alien chromosomal regions with homoeologous wheat chromosomes. Indeed, these addition lines were classified into four types based on the comparative mapping: 6PI, 6PII, 6PIII, and 6PIV. The different types of chromosome 6P possessed different desirable genes. For example, the 6PI type, containing three addition lines, carried genes conferring high numbers of kernels per spike and resistance to powdery mildew, important traits for wheat improvement. These results may prove valuable for promoting the development of conventional chromosome engineering techniques toward molecular chromosome engineering.

  16. Applying Least Absolute Shrinkage Selection Operator and Akaike Information Criterion Analysis to Find the Best Multiple Linear Regression Models between Climate Indices and Components of Cow's Milk.

    Science.gov (United States)

    Marami Milani, Mohammad Reza; Hense, Andreas; Rahmani, Elham; Ploeger, Angelika

    2016-07-23

    This study focuses on multiple linear regression models relating six climate indices (temperature humidity THI, environmental stress ESI, equivalent temperature index ETI, heat load HLI, modified HLI (HLI new ), and respiratory rate predictor RRP) with three main components of cow's milk (yield, fat, and protein) for cows in Iran. The least absolute shrinkage selection operator (LASSO) and the Akaike information criterion (AIC) techniques are applied to select the best model for milk predictands with the smallest number of climate predictors. Uncertainty estimation is employed by applying bootstrapping through resampling. Cross validation is used to avoid over-fitting. Climatic parameters are calculated from the NASA-MERRA global atmospheric reanalysis. Milk data for the months from April to September, 2002 to 2010 are used. The best linear regression models are found in spring between milk yield as the predictand and THI, ESI, ETI, HLI, and RRP as predictors with p -value < 0.001 and R ² (0.50, 0.49) respectively. In summer, milk yield with independent variables of THI, ETI, and ESI show the highest relation ( p -value < 0.001) with R ² (0.69). For fat and protein the results are only marginal. This method is suggested for the impact studies of climate variability/change on agriculture and food science fields when short-time series or data with large uncertainty are available.

  17. Specific binding of a Pop6/Pop7 heterodimer to the P3 stem of the yeast RNase MRP and RNase P RNAs.

    Science.gov (United States)

    Perederina, Anna; Esakova, Olga; Koc, Hasan; Schmitt, Mark E; Krasilnikov, Andrey S

    2007-10-01

    Pop6 and Pop7 are protein subunits of Saccharomyces cerevisiae RNase MRP and RNase P. Here we show that bacterially expressed Pop6 and Pop7 form a soluble heterodimer that binds the RNA components of both RNase MRP and RNase P. Footprint analysis of the interaction between the Pop6/7 heterodimer and the RNase MRP RNA, combined with gel mobility assays, demonstrates that the Pop6/7 complex binds to a conserved region of the P3 domain. Binding of these proteins to the MRP RNA leads to local rearrangement in the structure of the P3 loop and suggests that direct interaction of the Pop6/7 complex with the P3 domain of the RNA components of RNases MRP and P may mediate binding of other protein components. These results suggest a role for a key element in the RNase MRP and RNase P RNAs in protein binding, and demonstrate the feasibility of directly studying RNA-protein interactions in the eukaryotic RNases MRP and P complexes.

  18. Mechanisms of the p(He 6,He 5)d, p(He 6,α)t and p(He 6,t)α reactions

    International Nuclear Information System (INIS)

    Heiberg-Andersen, Henning

    2002-07-01

    This work was devoted to nucleon induced transfer reactions having the potential to probe the sub-cluster structures of the benchmark halo nucleus He 6, without the question marks the necessarily omitted exchange effects tend to put behind the CRC results when both collision partners are composite systems. Still, the exchange complications entered the analysis in an ironic way: The high Q-value of the p(He 6,α)t and p(He 6, t)α reactions caused sensitivity to the t - α optical potential at small radii, where the one-nucleon exchange effects are strongest. Since the attempt to throw them out of the extracted tau - α potential failed, it was necessary to extend the model space to avoid a too difficult modelling of the local equivalent t - α potential. By this step, all the complications originating from antisymmetrization within a larger model space entered the analysis. However, the persistent failures of the two-channel calculations of this and previous works can hardly be due to incorrect treatment of exchange effects only, so the loss of simplicity is probably illusory. Even at small angles, where the surface processes dominate, none of the two-channel calculations with various choices of t - α optical potentials managed to reproduce the p(He 6, α)t (p(He 6,t)α) data. This motivated inclusion of sequential transfers through the d + He 5 channel, where the sequential triton transfer process, included just for consistency in the coupling scheme of the four-channel calculation, turned out to be more influent than expected. The satisfactory reproduction of both the p(He 6, He 5)d and the p(He 6,α)t (p(He 6,t)α) data by the four-channel approach and the required re-normalization the real part of the p - He 6 optical potential are strong indications of substantial contributions from sequential transfer of the halo neutrons at this energy. The conclusions that can be drawn from this work are limited by the modest amount of available data. This limitation does

  19. Mechanisms of the p(He 6,He 5)d, p(He 6,{alpha})t and p(He 6,t){alpha} reactions

    Energy Technology Data Exchange (ETDEWEB)

    Heiberg-Andersen, Henning

    2002-07-01

    This work was devoted to nucleon induced transfer reactions having the potential to probe the sub-cluster structures of the benchmark halo nucleus He 6, without the question marks the necessarily omitted exchange effects tend to put behind the CRC results when both collision partners are composite systems. Still, the exchange complications entered the analysis in an ironic way: The high Q-value of the p(He 6,{alpha})t and p(He 6, t){alpha} reactions caused sensitivity to the t - {alpha} optical potential at small radii, where the one-nucleon exchange effects are strongest. Since the attempt to throw them out of the extracted tau - {alpha} potential failed, it was necessary to extend the model space to avoid a too difficult modelling of the local equivalent t - {alpha} potential. By this step, all the complications originating from antisymmetrization within a larger model space entered the analysis. However, the persistent failures of the two-channel calculations of this and previous works can hardly be due to incorrect treatment of exchange effects only, so the loss of simplicity is probably illusory. Even at small angles, where the surface processes dominate, none of the two-channel calculations with various choices of t - {alpha} optical potentials managed to reproduce the p(He 6, {alpha})t (p(He 6,t){alpha}) data. This motivated inclusion of sequential transfers through the d + He 5 channel, where the sequential triton transfer process, included just for consistency in the coupling scheme of the four-channel calculation, turned out to be more influent than expected. The satisfactory reproduction of both the p(He 6, He 5)d and the p(He 6,{alpha})t (p(He 6,t){alpha}) data by the four-channel approach and the required re-normalization the real part of the p - He 6 optical potential are strong indications of substantial contributions from sequential transfer of the halo neutrons at this energy. The conclusions that can be drawn from this work are limited by the

  20. Application of plutonium inventory measurement system (PIMS) and temporary canister verification system (TCVS) at RRP

    International Nuclear Information System (INIS)

    Noguchi, Yoshihiko; Nakamura, Hironobu; Adachi, Hideto; Iwamoto, Tomonori

    2004-01-01

    In U-Pu co-denitration area at Rokkasho Reprocessing Plant (RRP), Plutonium Inventory Measurement System (PIMS) and Temporary Canister Verification System (TCVS) are installed to provide efficient and effective safeguards. PIMS measures Pu quantity inside pipes and vessels installed in glove boxes by total neutron counting method. PIMS consists of total 142 neutron detector attached on the wall and top of glove boxes and neutron count rates of each detectors are related to each other to calculate Pu quantity of each process areas. In this moment, inactive calibration using Cf-source was completed. On the other hand, TCVS measures Pu quantity of canisters inside temporary storage by coincidence counting method and it will be installed before the active test. These systems have monitoring function as additional measures. This paper describes specification, performance and measurement principles of PIMS and TCVS. (author)

  1. Search for the signature of a halo structure in the p(6He,6Li)n reaction

    International Nuclear Information System (INIS)

    Cortina-Gil, M.D.; Roussel-Chomaz, P.; Mittig, W.; Casandjian, J.M.; Chartier, M.; Alamanos, N.; Auger, F.; Fekou-Youmbi, V.; Blumenfeld, Y.; and others.

    1995-01-01

    The elastic scattering p( 6 He, 6 He)p and charge exchange reaction p( 6 He, 6 Li)n have been measured in reverse kinematics with a secondary 6 He beam. The angular distributions for these reactions were obtained. In the case of the charge exchange reaction, the ratio of the cross section for the Gamow-Teller transition to the ground state, and for the Fermi transition to the isobaric analog state is a measure of the relative strength of the two components of the exchange interaction. This ratio is found compatible with existing systematics for stable T=1 nuclei, and no clear signature of a halo structure was found in the present data. (author)

  2. Evidence for presumable feline origin of sporadic G6P[9] rotaviruses in humans.

    Science.gov (United States)

    Pietsch, Corinna; Liebert, Uwe G

    2018-05-31

    Species A rotaviruses are highly diverse and impose a substantial burden to human and animal health. Interspecies transmission between livestock, domestic animals and humans is commonly observed, but spread of animal-like rotaviruses within the human population is limited. During the continued monitoring of rotavirus strains in Germany, an unusual G6P[9] rotavirus strain was detected in feces of a child. The complete rotavirus coding sequences revealed a unique G6-P[9]-I2-R2-C2-M2-A3-N2-T3-E2-H3 genotype constellation. The virus was phylogenetically related to feline G3P[9] strains and other human G6P[9] rotaviruses of presumable zoonotic origin. Analysis of primer binding sites of G6 specific genotyping revealed further evidence of a G6P[9] feline reservoir. Moreover, substantial deficits of conventional semi-nested PCR genotyping approaches in detecting contemporary G6P[9] were revealed. Rotavirus strain GER29-14 most likely resulted from a direct or recent interspecies transmission from a cat to human. Further studies could assess nucleic acid sequences and genotype constellations of feline rotavirus to confirm the likely feline origin of sporadic human G6P[9] strains. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Charge Carrier Transport and Photogeneration in P3HT:PCBM Photovoltaic Blends

    KAUST Repository

    Laquai, Fré dé ric; Andrienko, Denis; Mauer, Ralf; Blom, Paul W. M.

    2015-01-01

    mobility in the RR-P3HT phase of the polymer:fullerene photovoltaic blend, is dramatically affected by thermal annealing. The hole mobility increases more than three orders of magnitude and reaches a value of up to 2 × 10−4 cm2 V−1 s−1 after the thermal

  4. The results of radical retropubic prostatectomy and adjuvant therapy for pathologic stage C prostate cancer

    International Nuclear Information System (INIS)

    Schild, Steven E.; Wong, William W.; Grado, Gordon L.; Halyard, Michele Y.; Novicki, Donald E.; Swanson, Scott K.; Larson, Thayne R.; Ferrigni, Robert G.

    1996-01-01

    Purpose: The results of therapy in 288 men with pathologic Stage C prostate cancer who underwent radical retropubic prostatectomy (RRP) were analyzed to determine the effects of adjuvant therapy. Methods and Materials: Twenty-seven of the 288 patients received preoperative neoadjuvant hormonal therapy (leuprolide acetate). Postoperatively, 60 patients received adjuvant radiotherapy (RT) to the prostate bed. Follow-up ranged from 3 to 83 months (median = 32 months). Freedom from failure (FFF) was defined as maintaining a serum PSA level of ≤ 0.3 ng/ml. Results: The FFF was 61% at 3 years and 45% at 5 years for the entire group. The FFF following RRP plus RT was 75% at 3 years and 57% at 5 years as compared to 56% at 3 years and 40% at 5 years for RRP without RT (p = 0.049). The FFF following RRP plus neoadjuvant hormonal therapy was 58% at 3 years and 40% at 5 years as compared to 60% at 3 years and 45% at 5 years following RRP without hormonal therapy (p = 0.3). In patients without seminal vesicle (SV) invasion, the FFF was 81% at 3 and 5 years for RRP plus RT as compared to 61% at 3 years and 50% at 5 years for RRP without RT (p = 0.01). In patients with SV invasion, the FFF was 61% at 3 years and 36% at 5 years for RRP plus RT as compared to 44% at 3 years and 23% at 5 years for RRP without RT (p = 0.23). The projected local control rate was 83% at 5 years for those with RRP alone as compared to 100% for RRP plus RT (p = 0.02). Survival at 5 years was projected to be 92% and was not significantly altered by the administration of adjuvant therapies. Conclusions: Postoperative RT was associated with significantly improved local control and FFF rates, especially in patients with tumors which did not involve the seminal vesicles

  5. Human papillomavirus type 6 and 11 genetic variants found in 71 oral and anogenital epithelial samples from Australia.

    Directory of Open Access Journals (Sweden)

    Jennifer A Danielewski

    Full Text Available Genetic variation of 49 human papillomavirus (HPV 6 and 22 HPV11 isolates from recurrent respiratory papillomatosis (RRP (n = 17, genital warts (n = 43, anal cancer (n = 6 and cervical neoplasia cells (n = 5, was determined by sequencing the long control region (LCR and the E6 and E7 genes. Comparative analysis of genetic variability was examined to determine whether different disease states resulting from HPV6 or HPV11 infection cluster into distinct variant groups. Sequence variation analysis of HPV6 revealed that isolates cluster into variants within previously described HPV6 lineages, with the majority (65% clustering to HPV6 sublineage B1 across the three genomic regions examined. Overall 72 HPV6 and 25 HPV11 single nucleotide variations, insertions and deletions were observed within samples examined. In addition, missense alterations were observed in the E6/E7 genes for 6 HPV6 and 5 HPV11 variants. No nucleotide variations were identified in any isolates at the four E2 binding sites for HPV6 or HPV11, nor were any isolates found to be identical to the HPV6 lineage A or HPV11 sublineage A1 reference genomes. Overall, a high degree of sequence conservation was observed between isolates across each of the regions investigated for both HPV6 and HPV11. Genetic variants identified a slight association with HPV6 and anogenital lesions (p = 0.04. This study provides important information on the genetic diversity of circulating HPV 6 and HPV11 variants within the Australian population and supports the observation that the majority of HPV6 isolates cluster to the HPV6 sublineage B1 with anogenital lesions demonstrating an association with this sublineage (p = 0.02. Comparative analysis of Australian isolates for both HPV6 and HPV11 to those from other geographical regions based on the LCR revealed a high degree of sequence similarity throughout the world, confirming previous observations that there are no geographically specific variants for these

  6. The Splitting of Double-component Active Asteroid P/2016 J1 (PANSTARRS)

    Energy Technology Data Exchange (ETDEWEB)

    Moreno, F.; Pozuelos, F. J. [Instituto de Astrofísica de Andalucía, CSIC, Glorieta de la Astronomía s/n, E-18008 Granada (Spain); Novaković, B. [Department of Astronomy, Faculty of Mathematics, University of Belgrade, Studentski trg 16, 11000 Belgrade (Serbia); Licandro, J.; Cabrera-Lavers, A. [Instituto de Astrofísica de Canarias, c/Vía Láctea s/n, E-38200 La Laguna, Tenerife (Spain); Bolin, Bryce [Laboratoire Lagrange, Université Côte d’Azur, Observatoire de la Côte d’Azur, CNRS, Blvd. de l’Observatoire, CS 34229, F-06304 Nice cedex 4 (France); Jedicke, Robert [University of Hawaii, Institute for Astronomy, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States); Gladman, Brett J. [Department of Physics and Astronomy, University of British Columbia, Vancouver, BC (Canada); Bannister, Michele T. [Astrophysics Research Centre, Queens University Belfast, Belfast BT7 1NN (United Kingdom); Gwyn, Stephen D. J. [NRC-Herzberg Astronomy and Astrophysics, National Research Council of Canada, 5071 West Saanich Road, Victoria, BC V9E 2E7 (Canada); Vereš, Peter [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109 (United States); Chambers, Kenneth; Chastel, Serge; Denneau, Larry; Flewelling, Heather; Huber, Mark; Schunová-Lilly, Eva; Magnier, Eugene; Wainscoat, Richard; Waters, Christopher, E-mail: fernando@iaa.es [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States); and others

    2017-03-01

    We present deep imaging observations, orbital dynamics, and dust-tail model analyses of the double-component asteroid P/2016 J1 (J1-A and J1-B). The observations were acquired at the Gran Telescopio Canarias (GTC) and the Canada–France–Hawaii Telescope (CFHT) from mid-March to late July of 2016. A statistical analysis of backward-in-time integrations of the orbits of a large sample of clone objects of P/2016 J1-A and J1-B shows that the minimum separation between them occurred most likely ∼2300 days prior to the current perihelion passage, i.e., during the previous orbit near perihelion. This closest approach was probably linked to a fragmentation event of their parent body. Monte Carlo dust-tail models show that those two components became active simultaneously ∼250 days before the current perihelion, with comparable maximum loss rates of ∼0.7 and ∼0.5 kg s{sup −1}, and total ejected masses of 8 × 10{sup 6} and 6 × 10{sup 6} kg for fragments J1-A and J1-B, respectively. Consequently, the fragmentation event and the present dust activity are unrelated. The simultaneous activation times of the two components and the fact that the activity lasted 6–9 months or longer, strongly indicate ice sublimation as the most likely mechanism involved in the dust emission process.

  7. Component tree analysis of cystovirus φ6 nucleocapsid Cryo-EM single particle reconstructions.

    Directory of Open Access Journals (Sweden)

    Lucas M Oliveira

    Full Text Available The 3-dimensional structure of the nucleocapsid (NC of bacteriophage φ6 is described utilizing component tree analysis, a topological and geometric image descriptor. The component trees are derived from density maps of cryo-electron microscopy single particle reconstructions. Analysis determines position and occupancy of structure elements responsible for RNA packaging and transcription. Occupancy of the hexameric nucleotide triphosphorylase (P4 and RNA polymerase (P2 are found to be essentially complete in the NC. The P8 protein lattice likely fixes P4 and P2 in place during maturation. We propose that the viral procapsid (PC is a dynamic structural intermediate where the P4 and P2 can attach and detach until held in place in mature NCs. During packaging, the PC expands to accommodate the RNA, and P2 translates from its original site near the inner 3-fold axis (20 sites to the inner 5-fold axis (12 sites with excess P2 positioned inside the central region of the NC.

  8. P450 reductase and cytochrome b5 interactions with cytochrome P450: Effects on house fly CYP6A1 catalysis

    OpenAIRE

    Murataliev, Marat B.; Guzov, Victor M.; Walker, F. Ann; Feyereisen, René

    2008-01-01

    The interactions of protein components of the xenobiotic-metabolizing cytochrome P450 system, CYP6A1, P450 reductase, and cytochrome b5 from the house fly (Musca domestica) have been characterized. CYP6A1 activity is determined by the concentration of the CYP6A1-P450 reductase complex, regardless of which protein is present in excess. Both holo- and apo-b5 stimulated CYP6A1 heptachlor epoxidase and steroid hydroxylase activities and influenced the regioselectivity of testosterone hydroxylatio...

  9. Functional Dissociation of Latency-Variable, Stimulus- and Response-Locked Target P3 Sub-components in Task-Switching.

    Science.gov (United States)

    Brydges, Christopher R; Barceló, Francisco

    2018-01-01

    Cognitive control warrants efficient task performance in dynamic and changing environments through adjustments in executive attention, stimulus and response selection. The well-known P300 component of the human event-related potential (ERP) has long been proposed to index "context-updating"-critical for cognitive control-in simple target detection tasks. However, task switching ERP studies have revealed both target P3 (300-350 ms) and later sustained P3-like potentials (400-1,200 ms) to first targets ensuing transition cues, although it remains unclear whether these target P3-like potentials also reflect context updating operations. To address this question, we applied novel single-trial EEG analyses-residue iteration decomposition (RIDE)-in order to disentangle target P3 sub-components in a sample of 22 young adults while they either repeated or switched (updated) task rules. The rationale was to revise the context updating hypothesis of P300 elicitation in the light of new evidence suggesting that "the context" consists of not only the sensory units of stimulation, but also associated motor units, and intermediate low- and high-order sensorimotor units, all of which may need to be dynamically updated on a trial by trial basis. The results showed functionally distinct target P3-like potentials in stimulus-locked, response-locked, and intermediate RIDE component clusters overlying parietal and frontal regions, implying multiple functionally distinct, though temporarily overlapping context updating operations. These findings support a reformulated version of the context updating hypothesis, and reveal a rich family of distinct target P3-like sub-components during the reactive control of target detection in task-switching, plausibly indexing the complex and dynamic workings of frontoparietal cortical networks subserving cognitive control.

  10. Comparison of biochemical failure rates between permanent prostate brachytherapy and radical retropubic prostatectomy as a function of posttherapy PSA nadir plus ‘X’

    International Nuclear Information System (INIS)

    Ahmed, Kamran A; Davis, Brian J; Mynderse, Lance A; Slezak, Jeffrey M; Bergstralh, Eric J; Wilson, Torrence M; Choo, C Richard

    2014-01-01

    Prostate-specific antigen (PSA) nadir + 2 ng/mL, also known as the Phoenix definition, is the definition most commonly used to establish biochemical failure (BF) after external beam radiotherapy for prostate cancer management. The purpose of this study is to compare BF rates between permanent prostate brachytherapy (PPB) and radical retropubic prostatectomy (RRP) as a function of PSA nadir plus varying values of X and examine the associated implications. We retrospectively searched for patients who underwent PPB or RRP at our institution between 1998 and 2004. Only primary patients not receiving androgen-deprivation therapy were included in the study. Three RRP patients were matched to each PPB patient on the basis of prognostic factors. BF rates were estimated for PSA nadirs + different values of X. A total of 1,164 patients were used for analysis: 873 in the RRP group and 291 in the PPB group. Patients were equally matched by clinical stage, biopsy Gleason sum, primary Gleason grade, and pretherapy PSA value. Median follow-up was 3.1 years for RRP patients and 3.6 years in the PPB group (P = .01). Using PSA nadir + 0.1 ng/mL for the definition of BF, the 5-year BF rate was 16.3% for PPB patients and 13.5% for RRP patients (P = .007), whereas at nadir + 2 ng/mL or greater, the BF rates were less than 3% and were indistinguishable between PPB and RRP patients. In a cohort of well-matched patients who had prostatectomy or brachytherapy, we examined BF as a function of nadir + X, where X was treated as a continuous variable. As X increases from 0.1 to 2.0 ng/mL, the BF curves converge, and above 2.0 ng/mL they are essentially indistinguishable. The data presented are of interest as BF definitions continue to evolve

  11. Recurrent respiratory papillomatosis: a longitudinal study comparing severity associated with human papilloma viral types 6 and 11 and other risk factors in a large pediatric population.

    Science.gov (United States)

    Wiatrak, Brian J; Wiatrak, Deborah W; Broker, Thomas R; Lewis, Linda

    2004-11-01

    tracheotomy, and to develop pulmonary disease. Patients receiving a diagnosis of RRP before 3 years of age had significantly higher severity scores, higher frequencies of surgical intervention, and greater likelihood of requiring adjuvant medical therapy. Patients with Medicaid insurance had significantly higher severity scores and required more frequent surgical debridement. Birth by cesarean section appeared to be a significant risk factor for more severe disease and necessity of more frequent surgical intervention. Statistical analysis of the relationships among epidemiological factors, HPV type, and clinical course revealed that patients with HPV-11 and patients younger than 3 years of age at RRP diagnosis are prone to develop more aggressive disease as represented by higher severity scores at endoscopic debridement, more frequent operative debridement procedures per year, a greater requirement for adjuvant therapy, and greater likelihood of tracheal disease with tracheotomy.

  12. Multiple isoforms of the human pentraxin serum amyloid P component

    DEFF Research Database (Denmark)

    Sørensen, Inge Juul; Andersen, Ove; Nielsen, EH

    1995-01-01

    Human serum amyloid P component (SAP) isolated from 20 healthy individuals was analyzed by anion exchange chromatography and isoelectric focusing (IEF) in order to investigate the existence of multiple forms of SAP and interindividual structural differences. Anion exchange chromatography showed one...... major and several minor subpopulations of SAP. IEF of all SAP isolates showed a previously unreported degree of heterogeneity with six isoelectric forms (pKi range 5.5-6.1) and with minor interindividual differences in respect of isoelectric points. Total enzymatic deglycosylation of SAP reduced...... the number of bands in IEF to two indicating the existence of two types of polypeptide chains....

  13. GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests shared genetic susceptibility with diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Karin E Smedby

    2011-04-01

    Full Text Available Non-Hodgkin lymphoma (NHL represents a diverse group of hematological malignancies, of which follicular lymphoma (FL is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (OR(combined  = 0.64, P(combined  = 2 × 10(-21 located 962 bp away from rs10484561 (r(2<0.1 in controls. After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:OR(adjusted  = 0.70, P(adjusted  =  4 × 10(-12; rs10484561:OR(adjusted  = 1.64, P(adjusted  = 5 × 10(-15. Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (OR(combined  = 1.36, P(combined  =  1.4 × 10(-7. Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.

  14. Identification of Bombyx mori bidensovirus VD1-ORF4 reveals a novel protein associated with viral structural component.

    Science.gov (United States)

    Li, Guohui; Hu, Zhaoyang; Guo, Xuli; Li, Guangtian; Tang, Qi; Wang, Peng; Chen, Keping; Yao, Qin

    2013-06-01

    Bombyx mori bidensovirus (BmBDV) VD1-ORF4 (open reading frame 4, ORF4) consists of 3,318 nucleotides, which codes for a predicted 1,105-amino acid protein containing a conserved DNA polymerase motif. However, its functions in viral propagation remain unknown. In the current study, the transcription of VD1-ORF4 was examined from 6 to 96 h postinfection (p.i.) by RT-PCR, 5'-RACE revealed the transcription initiation site of BmBDV ORF4 to be -16 nucleotides upstream from the start codon, and 3'-RACE revealed the transcription termination site of VD1-ORF4 to be +7 nucleotides downstream from termination codon. Three different proteins were examined in the extracts of BmBDV-infected silkworms midguts by Western blot using raised antibodies against VD1-ORF4 deduced amino acid, and a specific protein band about 53 kDa was further detected in purified virions using the same antibodies. Taken together, BmBDV VD1-ORF4 codes for three or more proteins during the viral life cycle, one of which is a 53 kDa protein and confirmed to be a component of BmBDV virion.

  15. The RNA Exosome Channeling and Direct Access Conformations Have Distinct In Vivo Functions

    Directory of Open Access Journals (Sweden)

    Jaeil Han

    2016-09-01

    Full Text Available The RNA exosome is a 3′–5′ ribonuclease complex that is composed of nine core subunits and an essential catalytic subunit, Rrp44. Two distinct conformations of Rrp44 were revealed in previous structural studies, suggesting that Rrp44 may change its conformation to exert its function. In the channeling conformation, (Rrp44ch, RNA accesses the active site after traversing the central channel of the RNA exosome, whereas in the other conformation, (Rrp44da, RNA gains direct access to the active site. Here, we show that the Rrp44da exosome is important for nuclear function of the RNA exosome. Defects caused by disrupting the direct access conformation are distinct from those caused by channel-occluding mutations, indicating specific functions for each conformation. Our genetic analyses provide in vivo evidence that the RNA exosome employs a direct-access route to recruit specific substrates, indicating that the RNA exosome uses alternative conformations to act on different RNA substrates.

  16. An experimental study on providing a scientific evidence for seven-time alcohol-steaming of Rhei Rhizoma when clinically used.

    Science.gov (United States)

    Sim, Yeomoon; Oh, Hyein; Oh, Dal-Seok; Kim, Namkwon; Gu, Pil Sung; Choi, Jin Gyu; Kim, Hyo Geun; Kang, Tong Ho; Oh, Myung Sook

    2015-10-27

    Rhei Rhizoma (RR) has been widely used as laxative and processed to alter its therapeutic actions or reduce its side effects. In this study, we evaluated experimentally the clinical application guideline that RR should be alcohol-steamed seven times before being used in elderly patients, as described in Dongeuibogam, the most famous book on Korean traditional medicine. Unprocessed RR (RR-U) was soaked in rice wine, steamed and then fully dried (RR-P1). The process was repeated four (RR-P4) or seven times (RR-P7). Reversed-phase high-performance liquid chromatography was used to determine the RR-U, RR-P1, RR-P4 and RR-P7 (RRs) constituents. To evaluate the effect of RRs on liver toxicity, human hepatoma cells (HepG2) were treated with RRs at 100 μg/mL for 4 h and then cell viabilities were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. To confirm the effects in vivo, 5-week-old male Sprague-Dawley rats were treated with RRs at 3 g/kg/day for 21 days. Body weight and serum biochemical parameters were measured and liver histology was assessed. The levels of sennosides decreased in processed RRs in an iteration-dependent manner, while the emodin level was unaffected. In HepG2 cells, cell viability was reduced with RR-U, while the toxicity decreased according to the number of processing cycles. The changes in body weight, relative liver weight and liver enzymes of RR-U-treated rats were reduced in processed RRs-treated rats. Histopathological analysis indicated swelling and cholestasis improved following seven times alcohol-steaming cycles. These results provide experimental evidence that RR-P7 almost completely reduces RR hepatotoxicity.

  17. Relativistic and non-relativistic electronic molecular-structure calculations for dimers of 4p-, 5p-, and 6p-block elements.

    Science.gov (United States)

    Höfener, Sebastian; Ahlrichs, Reinhart; Knecht, Stefan; Visscher, Lucas

    2012-12-07

    We report results of non-relativistic and two-component relativistic single-reference coupled-cluster with single and double and perturbative triple excitations [CCSD(T)] treatments for the 4p-block dimers Ga(2) to Br(2) , the 5p-block dimers In(2) to I(2) , and their atoms. Extended basis sets up to pentuple zeta are employed and energies extrapolated to the complete basis-set limit. Relativistic and non-relativistic results for the dissociation energy D(e) are in close agreement with each other and previously published data, provided non-relativistic or scalar-relativistic results are corrected for spin-orbit contributions taken from the literature. An exception is Te(2) where theoretical results scatter by 0.085 eV. By virtue of this agreement it is unexpected that comparison with the experimental D(0) or D(e) dissociation energies (zero-point vibrational effects are negligible in this context) reveal errors larger than 0.1 eV for Ga(2), Ge(2), and Sb(2). Only relativistic treatments are presented for the 6p-block cases Tl(2) to At(2). Sufficient agreement with experimental data is found only for Pb(2) and Bi(2), the deviation of the computed and experimental D(0) values for Po(2) is again larger than 0.1 eV. Deviations of 0.1 eV between the computed and experimental D(0) values are a major reason for concern and call for additional investigations in both fields to clarify the situation. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Tumour suppressor protein p53 regulates the stress activated bilirubin oxidase cytochrome P450 2A6

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Hao, E-mail: hao.hu1@uqconnect.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Yu, Ting, E-mail: t.yu2@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Arpiainen, Satu, E-mail: Satu.Juhila@orion.fi [Institute of Biomedicine, Department of Pharmacology and Toxicology and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu (Finland); Lang, Matti A., E-mail: m.lang@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Hakkola, Jukka, E-mail: Jukka.hakkola@oulu.fi [Institute of Biomedicine, Department of Pharmacology and Toxicology and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu (Finland); Abu-Bakar, A' edah, E-mail: a.abubakar@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia)

    2015-11-15

    Human cytochrome P450 (CYP) 2A6 enzyme has been proposed to play a role in cellular defence against chemical-induced oxidative stress. The encoding gene is regulated by various stress activated transcription factors. This paper demonstrates that p53 is a novel transcriptional regulator of the gene. Sequence analysis of the CYP2A6 promoter revealed six putative p53 binding sites in a 3 kb proximate promoter region. The site closest to transcription start site (TSS) is highly homologous with the p53 consensus sequence. Transfection with various stepwise deletions of CYP2A6-5′-Luc constructs – down to − 160 bp from the TSS – showed p53 responsiveness in p53 overexpressed C3A cells. However, a further deletion from − 160 to − 74 bp, including the putative p53 binding site, totally abolished the p53 responsiveness. Electrophoretic mobility shift assay with a probe containing the putative binding site showed specific binding of p53. A point mutation at the binding site abolished both the binding and responsiveness of the recombinant gene to p53. Up-regulation of the endogenous p53 with benzo[α]pyrene – a well-known p53 activator – increased the expression of the p53 responsive positive control and the CYP2A6-5′-Luc construct containing the intact p53 binding site but not the mutated CYP2A6-5′-Luc construct. Finally, inducibility of the native CYP2A6 gene by benzo[α]pyrene was demonstrated by dose-dependent increases in CYP2A6 mRNA and protein levels along with increased p53 levels in the nucleus. Collectively, the results indicate that p53 protein is a regulator of the CYP2A6 gene in C3A cells and further support the putative cytoprotective role of CYP2A6. - Highlights: • CYP2A6 is an immediate target gene of p53. • Six putative p53REs located on 3 kb proximate CYP2A6 promoter region. • The region − 160 bp from TSS is highly homologous with the p53 consensus sequence. • P53 specifically bind to the p53RE on the − 160 bp region. • HNF4

  19. 16 CFR 1509.6 - Component-spacing test method.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Component-spacing test method. 1509.6 Section 1509.6 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT... applied to the wedge perpendicular to the plane of the crib side. ...

  20. Tumour necrosis factor and interleukin-6 production induced by components associated with merozoite proteins of Plasmodium falciparum

    DEFF Research Database (Denmark)

    Jakobsen, P H; Moon, R; Ridley, R G

    1993-01-01

    purified from culture supernatants, using immobilized monoclonal antibodies specific for RAP-1 or MSP-1, stimulated normal human mononuclear cells to produce TNF and IL-6 in vitro. However, stimulation of TNF was absent, and that of IL-6 was reduced, when the antigens were purified from detergent extracts...... of infected erythrocytes. These results indicate that the RAP-1 and MSP-1 proteins themselves do not stimulate the production of TNF. Instead, other components associating with these exoantigens may be responsible for the TNF production. Mouse antisera blocking TNF production stimulated by P. yoelii...... exoantigens also blocked TNF production stimulated by material affinity purified from P. falciparum culture supernatants using RAP-1 specific monoclonal antibody, indicating the conserved structure of the TNF inducing component....

  1. Structural evolution of the P22-like phages: Comparison of Sf6 and P22 procapsid and virion architectures

    Energy Technology Data Exchange (ETDEWEB)

    Parent, Kristin N. [University of California, San Diego, Department of Chemistry and Biochemistry, La Jolla, CA 92093 (United States); Gilcrease, Eddie B. [University of Utah School of Medicine, Division of Microbiology and Immunology, Department of Pathology, Salt Lake City, UT 84112 (United States); Casjens, Sherwood R., E-mail: sherwood.casjens@path.utah.edu [University of Utah School of Medicine, Division of Microbiology and Immunology, Department of Pathology, Salt Lake City, UT 84112 (United States); Baker, Timothy S., E-mail: tsb@ucsd.edu [University of California, San Diego, Department of Chemistry and Biochemistry, La Jolla, CA 92093 (United States); University of California, San Diego, Division of Biological Sciences, La Jolla, CA 92093 (United States)

    2012-06-05

    Coat proteins of tailed, dsDNA phages and in herpesviruses include a conserved core similar to the bacteriophage HK97 subunit. This core is often embellished with other domains such as the telokin Ig-like domain of phage P22. Eighty-six P22-like phages and prophages with sequenced genomes share a similar set of virion assembly genes and, based on comparisons of twelve viral assembly proteins (structural and assembly/packaging chaperones), these phages are classified into three groups (P22-like, Sf6-like, and CUS-3-like). We used cryo-electron microscopy and 3D image reconstruction to determine the structures of Sf6 procapsids and virions ({approx} 7 A resolution), and the structure of the entire, asymmetric Sf6 virion (16-A resolution). The Sf6 coat protein is similar to that of P22 yet it has differences in the telokin domain and in its overall quaternary organization. Thermal stability and agarose gel experiments show that Sf6 virions are slightly less stable than those of P22. Finally, bacterial host outer membrane proteins A and C were identified in lipid vesicles that co-purify with Sf6 particles, but are not components of the capsid.

  2. Intervening to Reduce Suicide Risk in Veterans with Substance Use Disorders

    Science.gov (United States)

    2015-01-01

    Other Support for Dr. Valenstein: 1. Effort ended on NIH/ NIA P01 AG031098 (PI – Cutler). 2. Effort ended on DoD W81XWH-11-2-0059 (PI – Hunt). 3...Effort started on VA QUERI RRP 12-511 (PI – Zivin). 19. Effort started on VA QUERI RRP 12- 505 (PI – Pfeiffer). OTHER SUPPORT VALENSTEIN...Pfeiffer, P.) 11/01/13 – 02/28/15 1.2 calendar VA MH-QUERI RRP 12- 505 $90,942 Technology-assisted peer support for recently hospitalized

  3. Salivaricin P, One of a Family of Two-Component Antilisterial Bacteriocins Produced by Intestinal Isolates of Lactobacillus salivarius▿

    Science.gov (United States)

    Barrett, Eoin; Hayes, Maria; O'Connor, Paula; Gardiner, Gillian; Fitzgerald, Gerald F.; Stanton, Catherine; Ross, R. Paul; Hill, Colin

    2007-01-01

    Lactobacillus salivarius DPC6005, a porcine intestinal isolate, produces a two-component bacteriocin, salivaricin P, with homology to ABP-118 produced by a human probiotic L. salivarius strain. Indeed, molecular characterization revealed that while the peptides Sln1 and ABP-118α are identical, their companion peptides (Sln2 and ABP-118β, respectively) differ by two amino acids. This observation suggests that two-component bacteriocins may be a common feature of intestinal L. salivarius strains. PMID:17416691

  4. The 4p-5d, 6d and 4p-6s, 7s transitions of Mo IX

    International Nuclear Information System (INIS)

    Khatoon, S.; Chaghtai, M.S.Z.; Rahimullah, K.

    1979-01-01

    The transitions 4p-5d, 6d and 4p-6s, 7s have been studied for the first time in Mo IX. The authors have identified 42 4p-5d, 36 4p-6d, 22 4p-6s and 22 4p-7s transitions, establishing 16 4p 3 5d, 14 4p 3 6d and all the ten 4p 3 6s, 7s levels of the spectrum concerned. The ionization energy is estimated to be (1 323 700 +- 700)cm -1 or (164.11 +- 0.09)eV. The spectrum was recorded in sliding and open spark discharges with a 5 m grazing incidence spectrograph of Lund University (Sweden) from about 40 A to 440 A. (Auth.)

  5. Effect of Recycled Rubber Particles and Silica on Tensile and Tear Properties of Natural Rubber Composites

    Directory of Open Access Journals (Sweden)

    Velu CHANDRAN

    2016-05-01

    Full Text Available Application of scrap rubber and worn out tires in natural rubber compounds has been studied. The scrap rubber can, however, be recycled and compounded with natural rubber and thus can be generated as a rubber composite. In this work, recycled rubber particles (RRP were prepared using pulverization process. Then, RRP was blended with natural rubber and silica compounds, and it was synthesized by two- roll mill and hydraulic press at specified operating conditions. The samples ranging from 0 to 40 phr of RRP loaded with silica were used as constant filler. The mechanical properties and morphological analysis were carried out. The results showed that tensile strength and elongation at break gradually decreased with increasing RRP loading in natural rubber and silica compounds. Tensile modulus went down at 10 phr of RRP and then showed an increasing trend. Hardness increased up to 30 phr of RRP and tear strength increased up to 20 phr of RRP. A comparative study was also carried out with virgin natural rubber vulcanizates. The incorporation of RRP and silica up to 20 phr in natural rubber did not lower the performance of rubber articles. Morphological studies revealed that better filler dispersion, interfacial adhesion, and cross link density could increase the tensile and tear strengths.DOI: http://dx.doi.org/10.5755/j01.ms.22.2.7330

  6. Haploinsufficiency for Core Exon Junction Complex Components Disrupts Embryonic Neurogenesis and Causes p53-Mediated Microcephaly.

    Directory of Open Access Journals (Sweden)

    Hanqian Mao

    2016-09-01

    Full Text Available The exon junction complex (EJC is an RNA binding complex comprised of the core components Magoh, Rbm8a, and Eif4a3. Human mutations in EJC components cause neurodevelopmental pathologies. Further, mice heterozygous for either Magoh or Rbm8a exhibit aberrant neurogenesis and microcephaly. Yet despite the requirement of these genes for neurodevelopment, the pathogenic mechanisms linking EJC dysfunction to microcephaly remain poorly understood. Here we employ mouse genetics, transcriptomic and proteomic analyses to demonstrate that haploinsufficiency for each of the 3 core EJC components causes microcephaly via converging regulation of p53 signaling. Using a new conditional allele, we first show that Eif4a3 haploinsufficiency phenocopies aberrant neurogenesis and microcephaly of Magoh and Rbm8a mutant mice. Transcriptomic and proteomic analyses of embryonic brains at the onset of neurogenesis identifies common pathways altered in each of the 3 EJC mutants, including ribosome, proteasome, and p53 signaling components. We further demonstrate all 3 mutants exhibit defective splicing of RNA regulatory proteins, implying an EJC dependent RNA regulatory network that fine-tunes gene expression. Finally, we show that genetic ablation of one downstream pathway, p53, significantly rescues microcephaly of all 3 EJC mutants. This implicates p53 activation as a major node of neurodevelopmental pathogenesis following EJC impairment. Altogether our study reveals new mechanisms to help explain how EJC mutations influence neurogenesis and underlie neurodevelopmental disease.

  7. Refined study of the interaction between HIV-1 p6 late domain and ALIX

    Directory of Open Access Journals (Sweden)

    Gerlier Denis

    2008-05-01

    Full Text Available Abstract The interaction between the HIV-1 p6 late budding domain and ALIX, a class E vacuolar protein sorting factor, was explored by using the yeast two-hybrid approach. We refined the ALIX binding site of p6 as being the leucine triplet repeat sequence (Lxx4 (LYPLTSLRSLFG. Intriguingly, the deletion of the C-terminal proline-rich region of ALIX prevented detectable binding to p6. In contrast, a four-amino acid deletion in the central hinge region of p6 increased its association with ALIX as shown by its ability to bind to ALIX lacking the proline rich domain. Finally, by using a random screening approach, the minimal ALIX391–510 fragment was found to specifically interact with this p6 deletion mutant. A parallel analysis of ALIX binding to the late domain p9 from EIAV revealed that p6 and p9, which exhibit distinct ALIX binding motives, likely bind differently to ALIX. Altogether, our data support a model where the C-terminal proline-rich domain of ALIX allows the access of its binding site to p6 by alleviating a conformational constraint resulting from the presence of the central p6 hinge.

  8. Backward elastic p3He-scattering and high momentum components of 3He wave function

    International Nuclear Information System (INIS)

    Uzikov, Yu.N.

    1998-01-01

    It is shown that owing to a dominance of np-pair transfer mechanism of backward elastic p 3 He-scattering for incident proton kinetic energies T p > 1 GeV the cross section of this process is defined mainly by the values of the Faddeev component of the wave function of 3 He nucleus, φ 23 (q 23 , p 1 ), at high relative momenta q 23 > 0.6 GeV/c of the NN-pair in the 1 S 0 -state and at low spectator momenta p 1 ∼ 0 - 0.2 GeV/c

  9. Model of human recurrent respiratory papilloma on chicken embryo chorioallantoic membrane for tumor angiogenesis research.

    Science.gov (United States)

    Uloza, Virgilijus; Kuzminienė, Alina; Palubinskienė, Jolita; Balnytė, Ingrida; Ulozienė, Ingrida; Valančiūtė, Angelija

    2017-07-01

    We aimed to develop a chick embryo chorioallantoic membrane (CAM) model of recurrent respiratory papilloma (RPP) and to evaluate its morphological and morphometric characteristics, together with angiogenic features. Fresh RRP tissue samples obtained from 13 patients were implanted in 174 chick embryo CAMs. Morphological, morphometric, and angiogenic changes in the CAM and chorionic epithelium were evaluated up until 7 days after the implantation. Immunohistochemical analysis (34βE12, Ki-67, MMP-9, PCNA, and Sambucus nigra staining) was performed to detect cytokeratins and endothelial cells and to evaluate proliferative capacity of the RRP before and after implantation on the CAM. The implanted RRP tissue samples survived on CAM in 73% of cases while retaining their essential morphologic characteristics and proliferative capacity of the original tumor. Implants induced thickening of both the CAM (241-560%, p=0.001) and the chorionic epithelium (107-151%, p=0.001), while the number of blood vessels (37-85%, p=0.001) in the CAM increased. The results of the present study confirmed that chick embryo CAM is a relevant host for serving as a medium for RRP fresh tissue implantation. The CAM assay demonstrated the specific RRP tumor growth pattern after implantation and provided the first morphological and morphometric characterization of the RRP CAM model that opens new horizons in studying this disease.

  10. Distribution of N-isopropyl-p-(I-123)iodoamphetamine among the peripheral blood components

    International Nuclear Information System (INIS)

    Kumazaki, Satoshi; Oriuchi, Noboru; Tomiyoshi, Katsumi; Inoue, Tomio; Sasaki, Yasuhito.

    1990-01-01

    With the purpose to clarify dynamics of N-isopropyl-p-[I-123]iodoamphetamine (I-123 IMP) in the blood stream its binding to the peripheral blood components was determined by in vitro experiment. I-123 IMP was added to the peripheral venous blood obtained from healthy volunteers to be incubated for different length of time (0-30 min) at 37deg C. The blood was then separated into blood cells and plasma. From the latter platelet rich plasma were separated. Radioactivity in each blood component was counted in a well type scintillation counter respectively. To evaluate the affinity of I-123 IMP to red blood cell the component containing blood cells were washed repeatedly with salines. It was found that the fraction of radioactivity in the blood cell component was 68.0±6.3% (m±1 S.D.), which was higher than that in the plasma (32.0%±6.3%). The radioactivity in the platelet-rich plasma was only 1.7±1.1% of the total I-123 IMP activity. This percentage did not change by the incubation time. When Tc-99m DTPA was incubated with blood, radioactivity in the blood cell component was only 22.5%, which is further lowered by 32±2.1% after each washing to reach 6.8% after three times washing. In contrast the radioactivity of I-123 IMP in blood cell component remained as high as 31.1% after eight times washing. Almost constant fraction (8.20±0.57%) of radioactivity was freed into supernate by each washing. These findings suggest that a certain specific binding mechanism is involved in the binding of I-123 IMP to red blood cells. (author)

  11. p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD

    DEFF Research Database (Denmark)

    Harada, H; Andersen, Jens S.; Mann, M

    2001-01-01

    Cytokines often deliver simultaneous, yet distinct, cell growth and cell survival signals. The 70-kDa ribosomal protein S6 kinase (p70S6K) is known to regulate cell growth by inducing protein synthesis components. We purified membrane-based p70S6K as a kinase responsible for site-specific phospho...

  12. Dissecting mechanisms of nuclear mRNA surveillance in THO/sub2 complex mutants

    DEFF Research Database (Denmark)

    Rougemaille, Mathieu; Gudipati, Rajani Kanth; Olesen, Jens Raabjerg

    2007-01-01

    by appending oligo(A)-tails onto structured substrates. Another role of the nuclear exosome is that of mRNA surveillance. In strains harboring a mutated THO/Sub2p system, involved in messenger ribonucleoprotein particle biogenesis and nuclear export, the exosome-associated 3' 5' exonuclease Rrp6p is required...

  13. [Normative aspects of somatosensory evoked P300 components].

    Science.gov (United States)

    Louzã Neto, M R; Maurer, K; Neuhauser, B

    1989-06-01

    Using a somatosensory version of the oddball-paradigma the influence of age and gender on the P300-component and the comparison of the potential after stimulation of the right and left median nerve was studied in 30 healthy right handed volunteers (age: 20-35 years). Latency, amplitude, area and duration of the P300-potential were analysed. No relationship between age, gender and the P300-parameters were observed. The amplitude and the area of the potential obtained from the F3 electrode were greater after stimulation of the right median nerve compared to the potential after stimulation of the left median nerve. All other results were not significantly different. Strong positive correlations between the results after stimulation of the right and left median nerve were observed. These results showed that by a young group of volunteers age and gender did not influence the P300-component. Although the P300-Parameters had a between-subject variability, their mean remained constant over the study, their correlation coefficients were strong positive and the side of stimulation did not influence them (except for the electrode F3).

  14. The human core exosome interacts with differentially localized processive RNases

    DEFF Research Database (Denmark)

    Tomecki, Rafal; Kristiansen, Maiken Søndergaard; Lykke-Andersen, Søren

    2010-01-01

    The eukaryotic RNA exosome is a ribonucleolytic complex involved in RNA processing and turnover. It consists of a nine-subunit catalytically inert core that serves a structural function and participates in substrate recognition. Best defined in Saccharomyces cerevisiae, enzymatic activity comes...... from the associated subunits Dis3p (Rrp44p) and Rrp6p. The former is a nuclear and cytoplasmic RNase II/R-like enzyme, which possesses both processive exo- and endonuclease activities, whereas the latter is a distributive RNase D-like nuclear exonuclease. Although the exosome core is highly conserved......, identity and arrangements of its catalytic subunits in different vertebrates remain elusive. Here, we demonstrate the association of two different Dis3p homologs--hDIS3 and hDIS3L--with the human exosome core. Interestingly, these factors display markedly different intracellular localizations: hDIS3...

  15. Mapping of epitopes on Poa p I and Lol p I allergens with monoclonal antibodies.

    Science.gov (United States)

    Lin, Z W; Ekramoddoullah, A K; Jaggi, K S; Dzuba-Fischer, J; Rector, E; Kisil, F T

    1990-01-01

    Allergen Poa p I isolated from the dialysed aqueous extract of Kentucky blue grass pollen by affinity chromatography with an anti-Lol p I murine monoclonal antibody (MAb) 290A-167 was previously shown to consist of a 35.8-kilodalton (kD) component with a pI of 6.4, designated as Poa p Ia, and a 33-kD component with a pI of 9.1, designated as Poa p Ib. The present study reports on the comparative antigenic analyses of these two components, using MAbs produced separately against Poa p I and Lol p I. Thus, anti-Poa p I MAbs 60 and 61 and anti-Lol p I MAb 290A-167 recognized Poa p Ia and Poa p Ib whereas anti-Poa p I MAbs 62, 63 and 64 and anti-Lol p I MAb 348A-6 recognized only Poa p Ia. The specificities of the MAbs were further resolved by comparing their respective abilities to inhibit the binding of 125I-Poa p I or 125I-Lol p I to the different MAbs prepared in the form of solid phase. These studies revealed that at least 4 distinct epitopes (designated as E1, E2, E3 and E4) were shared by both Poa p I and Lol p I. All 4 epitopes were present on Poa p Ia whereas only E1 and E3 were detected on Poa p Ib. E1 was recognized by MAbs 60 and 61, E2 by MAbs 62, 63 and 64, E3 by MAb 290A-167 and E4 by MAb 348A-6.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Study on the inclusion behavior of p-sulfonatocalix[6]arene with propranolol by spectrofluorometry

    Science.gov (United States)

    Li, Hui; Song, Jin-Ping; Chao, Jian-Bin; Shuang, Shao-Min; Dong, Chuan

    2012-11-01

    The inclusion interaction between propranolol (PPL) and p-sulfonatocalix[6]arene (SCX6) was investigated by fluorescence and 1H NMR spectroscopy. Influences of pH, temperature, ionic strength and the concentration of SCX6 were examined in detail. In phosphate buffer solution with pH 7.5, the fluorescence of PPL dramatically quenched upon addition of SCX6 revealing the formation of inclusion complexes between PPL and SCX6. The stoichiometric ratio was verified to be 1:1 by the continuous variation method. The inclusion constant of PPL-SCX6 complexes was calculated as 2.2 × 104 L/mol by the nonlinear curve fitting method. 1H NMR titration spectra testified that the aliphatic chain of PPL may be partially penetrated into the hydrophobic cavity of SCX6. This was confirmed by molecular dynamics calculations.

  17. Age of child, more than HPV type, is associated with clinical course in recurrent respiratory papillomatosis.

    Directory of Open Access Journals (Sweden)

    Farrel J Buchinsky

    2008-05-01

    Full Text Available RRP is a devastating disease in which papillomas in the airway cause hoarseness and breathing difficulty. The disease is caused by human papillomavirus (HPV 6 or 11 and is very variable. Patients undergo multiple surgeries to maintain a patent airway and in order to communicate vocally. Several small studies have been published in which most have noted that HPV 11 is associated with a more aggressive course.Papilloma biopsies were taken from patients undergoing surgical treatment of RRP and were subjected to HPV typing. 118 patients with juvenile-onset RRP with at least 1 year of clinical data and infected with a single HPV type were analyzed. HPV 11 was encountered in 40% of the patients. By our definition, most of the patients in the sample (81% had run an aggressive course. The odds of a patient with HPV 11 running an aggressive course were 3.9 times higher than that of patients with HPV 6 (Fisher's exact p = 0.017. However, clinical course was more closely associated with age of the patient (at diagnosis and at the time of the current surgery than with HPV type. Patients with HPV 11 were diagnosed at a younger age (2.4y than were those with HPV 6 (3.4y (p = 0.014. Both by multiple linear regression and by multiple logistic regression HPV type was only weakly associated with metrics of disease course when simultaneously accounting for age. CONCLUSIONS/SIGNIFICANCE ABSTRACT: The course of RRP is variable and a quarter of the variability can be accounted for by the age of the patient. HPV 11 is more closely associated with a younger age at diagnosis than it is associated with an aggressive clinical course. These data suggest that there are factors other than HPV type and age of the patient that determine disease course.

  18. Intracellular pH and 42.00 C heat response of CHO cells cultured at pH 6.6

    International Nuclear Information System (INIS)

    Cook, J.A.; Fox, M.H.

    1987-01-01

    The authors previously reported that cells under chronic low pH (6.6) conditions have altered thermotolerance. They further characterized both the doubling time (t/sub d/) and the internal pH (pH/sub 1/) of CHO cells continuously cultured at pH 6.6 for times greater than one year. The following differences were noted: 1) A t/sub d/ of 16 hr compared to a t/sub d/ of 12 hr for cells at normal pH (7.3) and a t/sub d/ of 25 hr for the acute low pH cells (pH = 6.6; incubation time = 4 hr). 2) A pH/sub i/ 0.1-0.15 pH units > normal cells and 0.3 pH units > acute low pH cells. 3) Survival at 42.0 0 C which differed from both normal and acute low pH cells. The chronic culture was still quite sensitive to 42.0 0 C treatments during the first 5 hr, but developed tolerance at a higher level than cells under acute low pH conditions. The pH/sub i/ of the chronic culture responded to 42.0 0 C heating in a manner similar to that for acute low pH cells. Whether this culture represents a normal response to long term low pH exposure, or was the response of a mutant population is at the present unknown

  19. Ligand-binding sites in human serum amyloid P component

    DEFF Research Database (Denmark)

    Heegaard, N.H.H.; Heegaard, Peter M. H.; Roepstorff, P.

    1996-01-01

    Amyloid P component (AP) is a naturally occurring glycoprotein that is found in serum and basement membranes, AP is also a component of all types of amyloid, including that found in individuals who suffer from Alzheimer's disease and Down's syndrome. Because AP has been found to bind strongly...

  20. Synergetic effect of pH and biochemical components on bacterial diversity during mesophilic anaerobic fermentation of biomass-origin waste.

    Science.gov (United States)

    Lü, F; Shao, L M; Bru, V; Godon, J J; He, P J

    2009-02-01

    To investigate the synergetic effect of pH and biochemical components on bacterial community structure during mesophilic anaerobic degradation of solid wastes with different origins, and under acidic or neutral conditions. The bacterial community in 16 samples of solid wastes with different biochemical compositions and origins was evaluated during mesophilic anaerobic degradation at acidic and neutral pH. Denaturing gradient gel electrophoresis (DGGE) and single-strand conformation polymorphism (SSCP) were used to compare the communities. Multivariate analysis of the DGGE and SSCP results revealed that most of the dominant microbes were dependent on the content of easily degradable carbohydrates in the samples. Furthermore, the dominant microbes were divided into two types, those that preferred an acid environment and those that preferred a neutral environment. A shift in pH was found to change their preference for medium substrates. Although most of the substrates with similar origin and biochemical composition had similar microbial diversity during fermentation, some microbes were found only in substrates with specific origins. For example, two microbes were only found in substrate that contained lignocellulose and animal protein without starch. These microbes were related to micro-organisms that are found in swine manure, as well as in other intestinal or oral niches. In addition, the distribution of fermentation products was less sensitive to the changes in pH and biochemical components than the microbial community. Bacterial diversity during anaerobic degradation of organic wastes was affected by both pH and biochemical components; however, pH exerted a greater effect. The results of this study reveal that control of pH may be an effective method to produce a stable bacterial community and relatively similar product distribution during anaerobic digestion of waste, regardless of variation in the waste feedstocks.

  1. Comparative efficiency of high (trip super phosphate) and low (rock phosphate) grade p nutrition source enriched with organic amendment in maize crop

    International Nuclear Information System (INIS)

    Sabah, N.U.; Sarwar, G.; Tahir, M.A.

    2016-01-01

    Pakistan falls under arid to semi-arid climate and therefore, Pakistani soils are sufferer of phosphorus deficiency. Costly phosphatic commercial fertilizers and their unavailability at the time of crop demand is the burning issue in Pakistan. Under such circumstances, use of locally available rock phosphate (RP) grasps the interest of researchers now a day. Pakistan has blessed with considerable quantity of cheaper low grade RP in Abbottabad and Hazara districts of KPK province. Due to this scenario, a pot experiment was carried out to evaluate growth efficiency of maize crop by adding organic manure fortified with RP in comparison with TSP in normal soil (pHs= 8.15, ECe= 1.28 dSm-1, SAR = 4.77 mmol L-1, saturation percentage = 29% and sandy clay loam texture). The study was comprised of 7 treatments replicated three times including: T1 = Control (0 P); T2 = Recommended NK + organic material; T3 = Recommended NK + RRP; T4 = Recommended NK + RRP + OM; T5 = Recommended NK + TSP; T6 = Recommended NK + TSP + OM and T7 = N + K + TSP + 0.5 Organic manure. It was concluded that integrated use of organic amendment with RP (Local Hazara Red Rock Phosphate) and TSP proved superior as compared to their sole use on maize crop growth. A significant increase in available P concentration of the growth medium was observed due to addition of organic material along with TSP as a source of P. Addition of organic material also enhanced the soil carbon level as compared to control. It can be concluded that rock phosphate (RP) could be an effective and economic substitution for TSP when it is integrated with suitable organic amendment with specific size. (author)

  2. Optical frequency measurements of 6s 2S1/2-6p 2P3/2 transition in a 133Cs atomic beam using a femtosecond laser frequency comb

    International Nuclear Information System (INIS)

    Gerginov, V.; Tanner, C.E.; Diddams, S.; Bartels, A.; Hollberg, L.

    2004-01-01

    Optical frequencies of the hyperfine components of the D 2 line in 133 Cs are determined using high-resolution spectroscopy and a femtosecond laser frequency comb. A narrow-linewidth probe laser excites the 6s 2 S 1/2 (F=3,4)→6p 2 P 3/2 (F=2,3,4,5) transition in a highly collimated atomic beam. Fluorescence spectra are taken by scanning the laser frequency over the excited-state hyperfine structure. The laser optical frequency is referenced to a Cs fountain clock via a reference laser and a femtosecond laser frequency comb. A retroreflected laser beam is used to estimate and minimize the Doppler shift due to misalignment between the probe laser and the atomic beam. We achieve an angular resolution on the order of 5x10 -6 rad. The final uncertainties (∼±5 kHz) in the frequencies of the optical transitions are a factor of 20 better than previous results [T. Udem et al., Phys. Rev. A 62, 031801 (2000).]. We find the centroid of the 6s 2 S 1/2 →6p 2 P 3/2 transition to be f D2 =351 725 718.4744(51) MHz

  3. IL-6 Impairs Myogenic Differentiation by Downmodulation of p90RSK/eEF2 and mTOR/p70S6K Axes, without Affecting AKT Activity

    Directory of Open Access Journals (Sweden)

    Michele Pelosi

    2014-01-01

    Full Text Available IL-6 is a multifaceted pleiotropic cytokine, which is produced by a variety of cell types and targets different cells and tissues. In physiological conditions, IL-6 can be locally and transiently produced by skeletal muscle and plays an important role in muscle homeostasis. Circulating IL-6 levels are normally very low or undetectable but are dramatically increased in several pathologic conditions. In this study, we aimed to define the potential molecular mechanisms underlying the effects of IL-6 on myogenic program. We explored the molecular mechanisms through which exogenous IL-6, or the conditioned medium from the murine C-26 adenocarcinoma cells (a cellular model that secretes high levels of IL-6 and induces cancer cachexia in mice, interferes with the myogenic program. Our study revealed that IL-6 induces the activation of the Stat3 signaling and promotes the downmodulation of the p90RSK/eEF2 and mTOR/p70S6K axes, while it does not affect the activation of AKT. We thus identified potential molecular mediators of the inhibitory effects of IL-6 on myogenic program.

  4. Characterizing the structure-function relationship reveals the mode of action of a novel antimicrobial peptide, P1, from jumper ant Myrmecia pilosula.

    Science.gov (United States)

    Tseng, Tien-Sheng; Tsai, Keng-Chang; Chen, Chinpan

    2017-06-01

    Microbial infections of antibiotic-resistant strains cause serious diseases and have a significant impact on public health worldwide, so novel antimicrobial drugs are urgently needed. Insect venoms, a rich source of bioactive components containing antimicrobial peptides (AMPs), are attractive candidates for new therapeutic agents against microbes. Recently, a novel peptide, P1, identified from the venom of the Australian jumper ant Myrmecia pilosula, showed potent antimicrobial activities against both Gram-negative and Gram-positive bacteria, but its structure-function relationship is unknown. Here, we used biochemical and biophysical techniques coupled with computational simulations to explore the mode of action of P1 interaction with dodecylphosphocholine (DPC) micelles as a model membrane system. Our circular dichroism (CD) and NMR studies revealed an amphipathic α-helical structure for P1 upon interaction with DPC micelles. A paramagnetic relaxation enhancement approach revealed that P1 orients its α-helix segment (F6-G14) into DPC micelles. In addition, the α-helix segment could be essential for membrane permeabilization and antimicrobial activity. Moreover, the arginine residues R8, R11, and R15 significantly contribute to helix formation and membrane-binding affinity. The lysine residue K19 of the C-terminus functionally guides P1 to interact with DPC micelles in the early interaction stage. Our study provides insights into the mode of action of P1, which is valuable in modifying and developing potent AMPs as antibiotic drugs.

  5. Novel QTL at chromosome 6p22 for alcohol consumption: Implications for the genetic liability of alcohol use disorders

    Science.gov (United States)

    Kos, Mark Z.; Glahn, David C.; Carless, Melanie A.; Olvera, Rene; McKay, D. Reese; Quillen, Ellen E.; Gelernter, Joel; Chen, Xiang-Ding; Deng, Hong-Wen; Kent, Jack W.; Dyer, Thomas D.; Göring, Harald H.H.; Curran, Joanne E.; Duggirala, Ravi; Blangero, John; Almasy, Laura

    2014-01-01

    Linkage studies of alcoholism have implicated several chromosome regions, leading to the successful identification of susceptibility genes, including ADH4 and GABRA2 on chromosome 4. Quantitative endophenotypes that are potentially closer to gene action than clinical endpoints offer a means of obtaining more refined linkage signals of genes that predispose alcohol use disorders (AUD). In this study we examine a self-reported measure of the maximum number of drinks consumed in a 24-hour period (abbreviated Max Drinks), a significantly heritable phenotype (h2 = 0.32 ± 0.05; P = 4.61 × 10−14) with a strong genetic correlation with AUD (ρg = 0.99 ± 0.13) for the San Antonio Family Study (n = 1,203). Genome-wide SNPs were analyzed using variance components linkage methods in the program SOLAR, revealing a novel, genome-wide significant QTL (LOD = 4.17; P = 5.85 × 10−6) for Max Drinks at chromosome 6p22.3, a region with a number of compelling candidate genes implicated in neuronal function and psychiatric illness. Joint analysis of Max Drinks and AUD status shows that the QTL has a significant non-zero effect on diagnosis (P = 4.04 × 10−3), accounting for 8.6% of the total variation. Significant SNP associations for Max Drinks were also identified at the linkage region, including one, rs7761213 (P = 2.14 × 10−4), obtained for an independent sample of Chinese families. Thus, our study identifies a potential risk locus for AUD at 6p22.3, with significant pleiotropic effects on the heaviness of alcohol consumption that may not be population specific. PMID:24692236

  6. Effect of regioregularity on recombination dynamics in inverted bulk heterojunction organic solar cells

    Science.gov (United States)

    Chandrasekaran, Naresh; Liu, Amelia C. Y.; Kumar, Anil; McNeill, Christopher R.; Kabra, Dinesh

    2018-01-01

    The effect of polymer regioregularity on the charge transport properties and bimolecular recombination rates of polymer-based solar cells is studied in detail using transient photovoltaic techniques. We compare organic solar cells fabricated with an ITO/ZnO/PEIE/P3HT:PCBM/MoO3/Ag structure using either 100% regioregular poly(3-hexylthiophene) (DF-P3HT) yielding an average power conversion efficiency (PCE) of 3.8  ±  0.3% or 92% regioregular P3HT (rr-P3HT) that yields an average PCE of 3.28  ±  0.4%. Transient photocurrent measurements reveal the presence of less mobile photoinduced charges in rr-P3HT:PCBM cells when compared to DF-P3HT:PCBM solar cells. Transient photovoltage measurements are used to establish the relationship between regioregularity and bimolecular recombination rate constant (k) finding that under 1 Sun, devices with high regioregularity have a longer τ despite having a higher k. The high value of k for the DF-P3HT:PCBM system as compared to the rr-P3HT:PCBM system is attributed to enhanced mobility and better charge transport of mobile charges in the DF-P3HT:PCBM system, consistent with enhanced fibrillar order in DF-P3HT films observed with transmission electron microscopy. We also note a slight decrease in cell open circuit voltage with increase in polymer regioregularity, which is due to the increase in k. Other recombination mechanisms such as trap-assisted recombination are found to be important in the lower regioregular P3HT device compounded by the reduced mobility and poor inter-chain ordering.

  7. P2Y6 Receptor Activation Promotes Inflammation and Tissue Remodeling in Pulmonary Fibrosis

    Science.gov (United States)

    Müller, Tobias; Fay, Susanne; Vieira, Rodolfo Paula; Karmouty-Quintana, Harry; Cicko, Sanja; Ayata, Cemil Korcan; Zissel, Gernot; Goldmann, Torsten; Lungarella, Giuseppe; Ferrari, Davide; Di Virgilio, Francesco; Robaye, Bernard; Boeynaems, Jean-Marie; Lazarowski, Eduardo R.; Blackburn, Michael R.; Idzko, Marco

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and very few available treatment options. The involvement of the purinergic receptor subtypes P2Y2 and P2X7 in fibrotic lung disease has been demonstrated recently. In this study, we investigated the role of P2Y6 receptors in the pathogenesis of IPF in humans and in the animal model of bleomycin-induced lung injury. P2Y6R expression was upregulated in lung structural cells but not in bronchoalveolar lavage (BAL) cells derived from IPF patients as well as in animals following bleomycin administration. Furthermore, BAL fluid levels of the P2Y6R agonist uridine-5′-diphosphate were elevated in animals with bleomycin-induced pulmonary fibrosis. Inflammation and fibrosis following bleomycin administration were reduced in P2Y6R-deficient compared to wild-type animals confirming the pathophysiological relevance of P2Y6R subtypes for fibrotic lung diseases. Experiments with bone marrow chimeras revealed the importance of P2Y6R expression on lung structural cells for pulmonary inflammation and fibrosis. Similar effects were obtained when animals were treated with the P2Y6R antagonist MRS2578. In vitro studies demonstrated that proliferation and secretion of the pro-inflammatory/pro-fibrotic cytokine IL-6 by lung fibroblasts are P2Y6R-mediated processes. In summary, our results clearly demonstrate the involvement of P2Y6R subtypes in the pathogenesis of pulmonary fibrosis. Thus, blocking pulmonary P2Y6 receptors might be a new target for the treatment of IPF. PMID:28878780

  8. P2Y6 Receptor Activation Promotes Inflammation and Tissue Remodeling in Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Tobias Müller

    2017-08-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a disease with a poor prognosis and very few available treatment options. The involvement of the purinergic receptor subtypes P2Y2 and P2X7 in fibrotic lung disease has been demonstrated recently. In this study, we investigated the role of P2Y6 receptors in the pathogenesis of IPF in humans and in the animal model of bleomycin-induced lung injury. P2Y6R expression was upregulated in lung structural cells but not in bronchoalveolar lavage (BAL cells derived from IPF patients as well as in animals following bleomycin administration. Furthermore, BAL fluid levels of the P2Y6R agonist uridine-5′-diphosphate were elevated in animals with bleomycin-induced pulmonary fibrosis. Inflammation and fibrosis following bleomycin administration were reduced in P2Y6R-deficient compared to wild-type animals confirming the pathophysiological relevance of P2Y6R subtypes for fibrotic lung diseases. Experiments with bone marrow chimeras revealed the importance of P2Y6R expression on lung structural cells for pulmonary inflammation and fibrosis. Similar effects were obtained when animals were treated with the P2Y6R antagonist MRS2578. In vitro studies demonstrated that proliferation and secretion of the pro-inflammatory/pro-fibrotic cytokine IL-6 by lung fibroblasts are P2Y6R-mediated processes. In summary, our results clearly demonstrate the involvement of P2Y6R subtypes in the pathogenesis of pulmonary fibrosis. Thus, blocking pulmonary P2Y6 receptors might be a new target for the treatment of IPF.

  9. GRIM-19 disrupts E6/E6AP complex to rescue p53 and induce apoptosis in cervical cancers.

    Directory of Open Access Journals (Sweden)

    Ying Zhou

    Full Text Available BACKGROUND: Our previous studies showed a down-regulation of GRIM-19 in primary human cervical cancers, and restoration of GRIM-19 induced tumor regression. The induction of tumor suppressor protein p53 ubiquitination and degradation by E6 oncoportein of high risk-HPV through forming a stable complex with E6AP is considered as a critical mechanism for cervical tumor development. The aims of this study were to determine the potential role of GRIM-19 in rescuing p53 protein and inducing cervical cancer cell apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The protein levels of GRIM-19 and p53 were detected in normal cervical tissues from 45 patients who underwent hysterectomy for reasons other than neoplasias of either the cervix or endometrium, and cervical cancer tissues from 60 patients with non-metastatic squamous epithelial carcinomas. Coimmunoprecipitation and GST pull-down assay were performed to examine the interaction of GRIM-19 with 18E6 and E6AP in vivo and in vitro respectively. The competition of 18E6 with E6AP in binding GRIM-19 by performing competition pull-down assays was designed to examine the disruption of E6/E6AP complex by GRIM-19. The augment of E6AP ubiquitination by GRIM-19 was detected in vivo and in vitro ubiquitination assay. The effects of GRIM-19-dependent p53 accumulation on cell proliferation, cell cycle, apoptosis were explored by MTT, flow cytometry and transmission electron microscopy respectively. The tumor suppression was detected by xenograft mouse model. CONCLUSION/SIGNIFICANCE: The levels of GRIM-19 and p53 were concurrently down regulated in cervical cancers. The restoration of GRIM-19 can induce ubiquitination and degradation of E6AP, and disrupt the E6/E6AP complex through the interaction of N-terminus of GRIM-19 with both E6 and E6AP, which protected p53 from degradation and promoted cell apoptosis. Tumor xenograft studies also revealed the suppression of p53 degradation in presence of GRIM-19. These data

  10. Effects of radiations on electronic components - Course IN2P3, release 6

    International Nuclear Information System (INIS)

    2007-01-01

    As many off-the-shelf electronic components are now present onboard satellites, launchers and planes, this course proposes an overview of effects radiations can have on these components, notably in space applications. A first part proposes an overview of radiative environments, and more particularly presents the space radiative environment (solar wind, solar flares, cosmic radiation, radiation belts). It also presents the atmospheric and Earth radiative environment due to cosmic radiation, the alpha radiation (origin of particles, particle flow), the radiative environment within an accelerator. The second part addresses the effects of these radiative environments on electronic components, and the associated standards and tests. It addresses cumulative effects and proposes a detailed analysis of the effects of an ionizing dose on a MOS transistor, an analysis of the effects of ionising dose rate on a bipolar NPN or PNP vertical or lateral transistor, an analysis of the effects of atomic displacements, and a discussion of structure modifications. The next part describes various single events: the Single Event Upset (SEU) and the Multiple Bit Upset (MBU) in the case of a SRAM, the SEL (Single Event Latch-up) phenomenon, the SEGR (Single Event Gate Rupture) phenomenon in the case of a Power MOSFET, and the SEB (Single Event Burnout) phenomenon in the case of a Power MOSFET

  11. Immunological response to quadrivalent HPV vaccine in treatment of recurrent respiratory papillomatosis.

    Science.gov (United States)

    Tjon Pian Gi, Robin E A; San Giorgi, Michel R M; Pawlita, Michael; Michel, Angelika; van Hemel, Bettien M; Schuuring, Ed M D; van den Heuvel, Edwin R; van der Laan, Bernard F A M; Dikkers, Frederik G

    2016-10-01

    Aim of this study was to explore influence of the quadrivalent HPV vaccine (Gardasil(®)) on the immune status of recurrent respiratory papillomatosis (RRP) patients. In retrospective observational study, six RRP patients who received the quadrivalent HPV vaccine and whose HPV seroreactivity was measured were included. Multiplex HPV Serology was used to determine HPV-specific antibodies pre- and post-vaccination. Surgical interventions and patient records were analyzed. Five HPV6 and 1 HPV11 infected patient were included. Mean antibody reactivity against the associated HPV type rose from 1125 median fluorescence intensity (MFI) pre-vaccination to 4690 MFI post-vaccination (p immunological increase can cause decrease in number of surgeries.

  12. Observation of the strongest 5s2 5p6 5d-(5s2 5p5 5d6s+5s25p6 7p) transitions in Au XI to Bi XV ions

    International Nuclear Information System (INIS)

    Churilov, S.S.; Joshi, Y.N.

    2001-01-01

    The spectra of gold till bismuth were studied in the 90-135 A region. Nine most intense lines belonging to the 5s 2 5p 6 5d-5s 2 5p 5 5d6s array were identified in Au XI to Bi XV ions. The 5s 2 5p 6 7p 2 P 3/2,1/2 levels in Au XI and the 5s 2 5p 6 7p 2 P 3/2 level in Hg XII were also identified. The observed wavelengths and intensities agree quite well with the Hartree-Fock calculations. (orig.)

  13. Interaction of serum amyloid P component with hexanoyl bis(d-proline) (CPHPC)

    Energy Technology Data Exchange (ETDEWEB)

    Kolstoe, Simon E. [University College London, Rowland Hill Street, London NW3 2PF (United Kingdom); Jenvey, Michelle C. [University of Southampton, Southampton SO17 1BJ (United Kingdom); Purvis, Alan [Imperial College London, London SW7 2AZ (United Kingdom); Light, Mark E. [University of Southampton, Southampton SO17 1BJ (United Kingdom); Thompson, Darren [University of Sussex, Falmer, Brighton BN1 9RQ (United Kingdom); Hughes, Peter; Pepys, Mark B.; Wood, Stephen P., E-mail: s.wood@ucl.ac.uk [University College London, Rowland Hill Street, London NW3 2PF (United Kingdom)

    2014-08-01

    Serum amyloid P component is a pentameric plasma glycoprotein that recognizes and binds to amyloid fibres in a calcium-dependent fashion and is likely to contribute to their deposition and persistence in vivo. Five molecules of the drug CPHPC avidly cross-link pairs of protein pentamers and the decameric complex is rapidly cleared in vivo. Crystal structures of the protein in complex with a bivalent drug and cadmium ions, which improve crystal quality, allow the definition of the preferred bound drug isomers. Under physiological conditions, the pentameric human plasma protein serum amyloid P component (SAP) binds hexanoyl bis(d-proline) (R-1-(6-[R-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl) pyrrolidine-2-carboxylic acid; CPHPC) through its d-proline head groups in a calcium-dependent interaction. Cooperative effects in binding lead to a substantial enhancement of affinity. Five molecules of the bivalent ligand cross-link and stabilize pairs of SAP molecules, forming a decameric complex that is rapidly cleared from the circulation by the liver. Here, it is reported that X-ray analysis of the SAP complex with CPHPC and cadmium ions provides higher resolution detail of the interaction than is observed with calcium ions. Conformational isomers of CPHPC observed in solution by HPLC and by X-ray analysis are compared with the protein-bound form. These are discussed in relation to the development of CPHPC to provide SAP depletion for the treatment of amyloidosis and other indications.

  14. The central role of mosquito cytochrome P450 CYP6Zs in insecticide detoxification revealed by functional expression and structural modelling.

    Science.gov (United States)

    Chandor-Proust, Alexia; Bibby, Jaclyn; Régent-Kloeckner, Myriam; Roux, Jessica; Guittard-Crilat, Emilie; Poupardin, Rodolphe; Riaz, Muhammad Asam; Paine, Mark; Dauphin-Villemant, Chantal; Reynaud, Stéphane; David, Jean-Philippe

    2013-10-01

    The resistance of mosquitoes to chemical insecticides is threatening vector control programmes worldwide. Cytochrome P450 monooxygenases (CYPs) are known to play a major role in insecticide resistance, allowing resistant insects to metabolize insecticides at a higher rate. Among them, members of the mosquito CYP6Z subfamily, like Aedes aegypti CYP6Z8 and its Anopheles gambiae orthologue CYP6Z2, have been frequently associated with pyrethroid resistance. However, their role in the pyrethroid degradation pathway remains unclear. In the present study, we created a genetically modified yeast strain overexpressing Ae. aegypti cytochrome P450 reductase and CYP6Z8, thereby producing the first mosquito P450-CPR (NADPH-cytochrome P450-reductase) complex in a yeast recombinant system. The results of the present study show that: (i) CYP6Z8 metabolizes PBAlc (3-phenoxybenzoic alcohol) and PBAld (3-phenoxybenzaldehyde), common pyrethroid metabolites produced by carboxylesterases, producing PBA (3-phenoxybenzoic acid); (ii) CYP6Z8 transcription is induced by PBAlc, PBAld and PBA; (iii) An. gambiae CYP6Z2 metabolizes PBAlc and PBAld in the same way; (iv) PBA is the major metabolite produced in vivo and is excreted without further modification; and (v) in silico modelling of substrate-enzyme interactions supports a similar role of other mosquito CYP6Zs in pyrethroid degradation. By playing a pivotal role in the degradation of pyrethroid insecticides, mosquito CYP6Zs thus represent good targets for mosquito-resistance management strategies.

  15. Spectral analysis of 5s25p2(6p+6d+7s) configurations of Ba VI

    International Nuclear Information System (INIS)

    Sharma, M.K.; Tauheed, A.; Rahimullah, K.

    2014-01-01

    The sixth spectrum of barium (Ba VI) has been investigated with the aid of experimental recordings made on a 3-m normal incidence vacuum spectrograph of Antigonish laboratory (Canada) in the wavelength region 300–2080 Å using triggered spark as an excitation source. The spectral analysis has been extended considerably to include new configuration the 5s 2 5p 2 6p in odd parity matrix and the 5s 2 5p 2 6d and 5s 2 5p 2 7s configurations in even parity matrix. Previously reported levels of the ground configuration (5s 2 5p 3 ) and three lowest excited configurations the 5s5p 4 , 5s 2 5p 2 5d and 5s 2 5p 2 6s have been confirmed and the two unknown levels of the 5s 2 5p 2 5d configuration with J=9/2, have now been established through the identification of transitions from the 5s 2 5p 2 6p levels. All twenty one levels of the 5s 2 5p 2 6p configuration and twenty nine levels out of thirty six of the 5s 2 5p 2 6d and 5s 2 5p 2 7s configurations have now been established. Hartree–Fock calculations involving configuration interactions support the analyses. The accuracy of our wavelength measurement is ±0.005 Å for sharp lines. - Highlights: • The spectrum of Ba was recorded on a 3-m spectrograph with triggered spark source. • Atomic transitions for Ba VI were identified to established new energy levels. • CI calculations with relativistic corrections were made for theoretical predictions. • Weighted oscillator strength (gf) and transition probabilities (gA) were calculated

  16. TAF6delta controls apoptosis and gene expression in the absence of p53.

    Directory of Open Access Journals (Sweden)

    Emmanuelle Wilhelm

    Full Text Available BACKGROUND: Life and death decisions of metazoan cells hinge on the balance between the expression of pro- versus anti-apoptotic gene products. The general RNA polymerase II transcription factor, TFIID, plays a central role in the regulation of gene expression through its core promoter recognition and co-activator functions. The core TFIID subunit TAF6 acts in vitro as an essential co-activator of transcription for the p53 tumor suppressor protein. We previously identified a splice variant of TAF6, termed TAF6delta that can be induced during apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the impact of TAF6delta on cell death and gene expression, we have employed modified antisense oligonucleotides to enforce expression of endogenous TAF6delta. The induction of endogenous TAF6delta triggered apoptosis in tumor cell lines, including cells devoid of p53. Microarray experiments revealed that TAF6delta activates gene expression independently of cellular p53 status. CONCLUSIONS: Our data define TAF6delta as a pivotal node in a signaling pathway that controls gene expression programs and apoptosis in the absence of p53.

  17. Native human serum amyloid P component is a single pentamer

    DEFF Research Database (Denmark)

    Sørensen, Inge Juul; Andersen, Ove; Nielsen, EH

    1995-01-01

    Serum amyloid P component (SAP) and C-reactive protein (CRP) are members of the pentraxin protein family. SAP is the precursor protein to amyloid P component present in all forms of amyloidosis. The prevailing notion is that SAP in circulation has the form of a double pentameric molecule (decamer...... by rocket immunoelectrophoresis and electron microscopy. Thus, electron micrographs of purified SAP showed a predominance of decamers. However, the decamer form of SAP reversed to single pentamers when purified SAP was incorporated into SAP-depleted serum....

  18. Biological and physicochemical properties of biosurfactants produced by Lactobacillus jensenii P6A and Lactobacillus gasseri P65.

    Science.gov (United States)

    Morais, I M C; Cordeiro, A L; Teixeira, G S; Domingues, V S; Nardi, R M D; Monteiro, A S; Alves, R J; Siqueira, E P; Santos, V L

    2017-09-19

    Lactobacillus species produce biosurfactants that can contribute to the bacteria's ability to prevent microbial infections associated with urogenital and gastrointestinal tracts and the skin. Here, we described the biological and physicochemical properties of biosurfactants produced by Lactobacillus jensenii P 6A and Lactobacillus gasseri P 65 . The biosurfactants produced by L. jensenii P 6A and L. gasseri P 65 reduced the water surface tension from 72 to 43.2 mN m -1 and 42.5 mN m -1 as their concentration increased up to the critical micelle concentration (CMC) values of 7.1 and 8.58 mg mL -1 , respectively. Maximum emulsifying activity was obtained at concentrations of 1 and 5 mg mL -1 for the P 6A and P 65 strains, respectively. The Fourier transform infrared spectroscopy data revealed that the biomolecules consist of a mixture of carbohydrates, lipids and proteins. The gas chromatography-mass spectrum analysis of L. jensenii P 6A biosurfactant showed a major peak for 14-methypentadecanoic acid, which was the main fatty acid present in the biomolecule; conversely, eicosanoic acid dominated the biosurfactant produced by L. gasseri P 65 . Although both biosurfactants contain different percentages of the sugars galactose, glucose and ribose; rhamnose was only detected in the biomolecule produced by L. jensenii P 6A . Emulsifying activities were stable after a 60-min incubation at 100 °C, at pH 2-10, and after the addition of potassium chloride and sodium bicarbonate, but not in the presence of sodium chloride. The biomolecules showed antimicrobial activity against clinical isolates of Escherichia coli and Candida albicans, with MIC values of 16 µg mL -1 , and against Staphylococcus saprophyticus, Enterobacter aerogenes and Klebsiella pneumoniae at 128 µg mL -1 . The biosurfactants also disrupted preformed biofilms of microorganisms at varying concentrations, being more efficient against E. aerogenes (64%) (P 6A biosurfactant), and E. coli (46

  19. Chiral synthesis of (Z)-3-cis-6,7-cis-9,10-diepoxyhenicosenes, sex pheromone components of the satin moth, Leucoma salicis.

    Science.gov (United States)

    Wimalaratne, Priyantha D C; Slessor, Keith N

    2004-06-01

    All four isomers of (Z)-3-cis-6,7-cis-9,10-diepoxyhenicosenes, 1-4, have been synthesized using D-xylose as the chirally pure starting material. D-Xylose was first converted to 2-deoxy-4,5-O-isopropylidene-3-t-butyldimethylsilyl-D-threopentose 11, via several steps of selective protection, dehydroxylation, and deprotection. Wittig coupling of 11 with nonyltriphenylphosphonium bromide followed by hydrogenation and acid catalyzed deprotection of hydroxyl groups yielded the chiral (2R,3R)-1,2,3-triol, 14, which was used as the precursor for the C-8 to C-21 unit of the (Z)-3-cis-6,7-cis-9,10-diepoxyhenicosenes. Selective tosylation of 14 followed by stereospecific cyclization yielded (2R,3R)-1,2-epoxytetradecan-3-ol, 16, which was then divergently converted to the t-butyldimethylsilyl ether 17 and tosylate 22, respectively. Establishment of the C-5 through C-7 unit of the target molecules was accomplished via regiospecific coupling of 17 with 1-t-butyldimethylsiloxy-2-propyne to form 18. Stepwise transformation of 18 via the formation of tosylate 19, desilylation, and stereospecific cyclization to form epoxy alcohol 20, followed by P2-Ni reduction yielded a key intermediate, allylic epoxy alcohol (Z)-2-(5S,6R)-cis-5,6-epoxyheptadecen-1-ol, 21. Similarly, the coupling of 22 with 1-t-butyldimethylsiloxy-2-propyne yielded 23, which was stereospecifically cyclized to form 24. Desilylation and P2-Ni reduction of 24 gave the antipodal intermediate, (Z)-2-(5R,6S)-cis-5,6-epoxyheptadecen-1-ol, 26. Asymmetric epoxidation of antipodes 21 and 26 with (L)- or (D)-diethyl tartrates resulted in the formation of diepoxy alcohols 27 and 29 from 21, and 33 and 31 from 26, respectively. Tosylation of these diepoxy alcohols followed by coupling with lithium dibutenyl cuprate yielded the four stereoisomers of (Z)-3-cis-6,7-cis-9,10-diepoxyhenicosenes, 1-4. Analysis of the retention characteristics of these materials revealed that one or both of the S*,R*,S*,R* stereoisomers comprise the

  20. Performance analysis of a Principal Component Analysis ensemble classifier for Emotiv headset P300 spellers.

    Science.gov (United States)

    Elsawy, Amr S; Eldawlatly, Seif; Taher, Mohamed; Aly, Gamal M

    2014-01-01

    The current trend to use Brain-Computer Interfaces (BCIs) with mobile devices mandates the development of efficient EEG data processing methods. In this paper, we demonstrate the performance of a Principal Component Analysis (PCA) ensemble classifier for P300-based spellers. We recorded EEG data from multiple subjects using the Emotiv neuroheadset in the context of a classical oddball P300 speller paradigm. We compare the performance of the proposed ensemble classifier to the performance of traditional feature extraction and classifier methods. Our results demonstrate the capability of the PCA ensemble classifier to classify P300 data recorded using the Emotiv neuroheadset with an average accuracy of 86.29% on cross-validation data. In addition, offline testing of the recorded data reveals an average classification accuracy of 73.3% that is significantly higher than that achieved using traditional methods. Finally, we demonstrate the effect of the parameters of the P300 speller paradigm on the performance of the method.

  1. Synthesis and biological activity of M6-P and M6-P analogs on fibroblast and keratinocyte proliferation.

    Science.gov (United States)

    Clavel, Caroline; Barragan-Montero, Véronique; Garric, Xavier; Molès, Jean-Pierre; Montero, Jean-Louis

    2005-09-01

    A new synthetic route to obtain the carboxylate analog of mannose 6-phosphate (M6-P) is presented. The effects of the M6-P, the carboxylate and two other analogs (the phosphonate and the alpha,beta ethylenic carboxylate) on the proliferation of human keratinocytes and dermal fibroblasts as well as on the proliferation of a murine fibroblast cell line, 3T3-J2 are tested. We observed that M6-P is a potent inhibitor of proliferation of both fibroblasts and keratinocytes. Among its analogs, the phosphonate showed a similar effect on human dermal fibroblasts but not on keratinocytes.

  2. Recurrent respiratory papillomatosis: HPV genotypes and risk of high-grade laryngeal neoplasia.

    Directory of Open Access Journals (Sweden)

    Turid Omland

    Full Text Available Patients with recurrent respiratory papillomatosis (RRP in Norway treated between 1987 and 2009 were recruited to this cohort study. They were followed from disease onset and data recorded until January 2012. Here, we describe the distribution of human papillomavirus (HPV genotypes, the prevalence of multiple HPV infections, and the risk of high-grade laryngeal neoplasia and respiratory tract invasive carcinoma in a large cohort of patients with RRP. We also examined whether HPV genotype, gender, age or clinical course are risk factors for this development. Clinical records and histological specimens were reviewed. Using formalin-fixed paraffin-embedded biopsies, HPV genotyping were performed by quantitative polymerase chain reaction assays identifying 15 HPV types. HPV-negative specimens were analyzed by metagenomic sequencing. Paraffin blocks were available in 224/238 patients. The DNA quality was approved in 221/224 cases. HPV DNA was detected in 207/221 patients and all were HPV 6 or HPV 11 positive, comprising HPV 6 in 133/207, HPV 11 in 40/207 cases and HPV 6/11 in 15/207 cases. Co-infection with one or two high-risk HPV types together with HPV 6 or HPV 11 was present in 19/207 patients. Metagenomic sequencing of 14 HPV-negative specimens revealed HPV 8 in one case. In total, 39/221 patients developed high-grade laryngeal neoplasia. 8/221 patients developed carcinoma of the respiratory tract (six patients with laryngeal carcinoma and two patients with lung carcinoma. High-grade laryngeal neoplasias were found more frequently in HPV-negative versus HPV-positive patients, (RR = 2.35, 95% CI 1.1, 4.99, as well as respiratory tract carcinomas (RR = 48, 95% CI 10.72, 214.91. In summary, the majority of RRP were associated with HPV 6 and/or 11. HPV-negative RRP biopsies occurred more frequently in adult-onset patients, and were associated with an increased risk of laryngeal neoplasia and carcinoma in the respiratory tract.

  3. Fasciola spp: Mapping of the MF6 epitope and antigenic analysis of the MF6p/HDM family of heme-binding proteins.

    Directory of Open Access Journals (Sweden)

    Victoria Martínez-Sernández

    Full Text Available MF6p/FhHDM-1 is a small cationic heme-binding protein which is recognized by the monoclonal antibody (mAb MF6, and abundantly present in parenchymal cells and secreted antigens of Fasciola hepatica. Orthologs of this protein (MF6p/HDMs also exist in other causal agents of important foodborne trematodiasis, such as Clonorchis sinensis, Opisthorchis viverrini and Paragonimus westermani. Considering that MF6p/FhHDM-1 is relevant for heme homeostasis in Fasciola and was reported to have immunomodulatory properties, this protein is expected to be a useful target for vaccination. Thus, in this study we mapped the epitope recognized by mAb MF6 and evaluated its antigenicity in sheep. The sequence of the MF6p/FhHDM-1 ortholog from F. gigantica (MF6p/FgHDM-1 was also reported. By means of ELISA inhibitions with overlapping synthetic peptides, we determined that the epitope recognized by mAb MF6 is located within the C-terminal moiety of MF6p/FhHDM-1, which is the most conserved region of MF6p/HDMs. By immunoblotting analysis of parasite extracts and ELISA inhibitions with synthetic peptides we also determined that mAb MF6 reacted with the same intensity with F. hepatica and F. gigantica, and in decreasing order of intensity with C. sinensis, O.viverrini and P. westermani orthologs. On the contrary, mAb MF6 showed no reactivity against Dicrocoelium dendriticum and Schistosoma mansoni. The study of the recognition of peptides covering different regions of MF6p/FhHDM-1 by sera from immunized sheep revealed that the C-terminal moiety is the most antigenic, thus being of potential interest for vaccination. We also demonstrated that the production of antibodies to MF6p/FhHDM-1 in sheep infected by F. hepatica occurs relatively early and follows the same pattern as those produced against L-cathepsins.

  4. Inhibition selectivity of grapefruit juice components on human cytochromes P450.

    Science.gov (United States)

    Tassaneeyakul, W; Guo, L Q; Fukuda, K; Ohta, T; Yamazoe, Y

    2000-06-15

    Five compounds including furanocoumarin monomers (bergamottin, 6', 7'-dihydroxybergamottin (DHB)), furanocoumarin dimers (4-¿¿6-hydroxy-71-¿(1-hydroxy-1-methyl)ethyl-4-methyl-6-(7-oxo-7H- furo¿3,2-g1benzopyran-4-yl)-4-hexenyl]oxy]-3,7-dimethyl- 2-octenyl]oxy]-7H-furo[3,2-g]¿1benzopyran-7-one (GF-I-1) and 4-¿¿6-hydroxy-7¿¿4-methyl-1-(1-methylethenyl)-6-(7-oxo-7H-furo¿3, 2-g1benzopyran-4-yl)-4-hexenylŏxy-3, 7-dimethyl-2-octenylŏxy-7H-furo¿3,2-g1benzopyran-7-one (GF-I-4)), and a sesquiterpene nootkatone have been isolated from grapefruit juice and screened for their inhibitory effects toward human cytochrome P450 (P450) forms using selective substrate probes. Addition of ethyl acetate extract of grapefruit juice into an incubation mixture resulted in decreased activities of CYP3A4, CYP1A2, CYP2C9, and CYP2D6. All four furanocoumarins clearly inhibited CYP3A4-catalyzed nifedipine oxidation in concentration- and time-dependent manners, suggesting that these compounds are mechanism-based inhibitors of CYP3A4. Of the furanocoumarins investigated, furanocoumarin dimers, GF-I-1 and GF-I-4, were the most potent inhibitors of CYP3A4. Inhibitor concentration required for half-maximal rate of inactivation (K(I)) values for bergamottin, DHB, GF-I-1, and GF-I-4 were calculated, respectively, as 40.00, 5. 56, 0.31, and 0.13 microM, whereas similar values were observed on their inactivation rate constant at infinite concentration of inhibitor (k(inact), 0.05-0.08 min(-1)). Apparent selectivity toward CYP3A4 does occur with the furanocoumarin dimers. In contrast, bergamottin showed rather stronger inhibitory effect on CYP1A2, CYP2C9, CYP2C19, and CYP2D6 than on CYP3A4. DHB inhibited CYP3A4 and CYP1A2 activities at nearly equivalent potencies. Among P450 forms investigated, CYP2E1 was the least sensitive to the inhibitory effect of furanocoumarin components. A sesquiterpene nootkatone has no significant effect on P450 activities investigated except for CYP2A6 and CYP2C19

  5. Revealing the equivalence of two clonal survival models by principal component analysis

    International Nuclear Information System (INIS)

    Lachet, Bernard; Dufour, Jacques

    1976-01-01

    The principal component analysis of 21 chlorella cell survival curves, adjusted by one-hit and two-hit target models, lead to quite similar projections on the principal plan: the homologous parameters of these models are linearly correlated; the reason for the statistical equivalence of these two models, in the present state of experimental inaccuracy, is revealed [fr

  6. Peri-operative comparison between daVinci-assisted radical prostatectomy and open radical prostatectomy in obese patients

    Science.gov (United States)

    Le, Carter Q.; Ho, Khai-Linh V.; Slezak, Jeffrey M.; Blute, Michael L.; Gettman, Matthew T.

    2007-02-01

    Introduction: While the effects of increasing body mass index on prostate cancer epidemiology and surgical approach have recently been studied, its effects on surgical outcomes are less clear. We studied the perioperative outcomes of obese (BMI >= 30) men treated with daVinci-assisted laparoscopic radical prostatectomy (DLP) and compared them to those treated with open radical retropubic prostatectomy (RRP) in a contemporary time frame. Method: After Institutional Review Board approval, we used the Mayo Clinic Radical Prostatectomy database to identify patients who had undergone DLP by a single surgeon and those who had undergone open RRP by a single surgeon between December 2002 and March 2005. Baseline demographics, peri- and post-operative courses, and complications were collected by retrospective chart review, and variables from the two cohorts compared using chi-square method and least-squares method of linear regression where appropriate. Results: 59 patients who had DLP and 76 undergoing RRP were available for study. Baseline demographics were not statistically different between the two cohorts. Although DLP had a significantly lower clinical stage than RRP (p=0.02), pathological stage was not statistically different (p=0.10). Transfusion rates, hospital stay, overall complications, and pathological Gleason were also not significantly different, nor were PSA progression, positive margin rate, or continence at 1 year. After bilateral nerve-sparing, erections suitable for intercourse with or without therapy at 1 year was 88.5% (23/26) for DLP and 61.2% (30/49) for RRP (p=0.01). Follow-up time was similar. Conclusion: For obese patients, DLP appears to have similar perioperative, as well as short-term oncologic and functional outcomes when compared to open RRP.

  7. Calumenin interacts with serum amyloid P component

    DEFF Research Database (Denmark)

    Vorum, H; Jacobsen, Christian; Honoré, Bent

    2000-01-01

    with calumenin in the presence of Ca(2+). Amino acid sequencing identified this protein as serum amyloid P component (SAP). Furthermore, we verified and characterized the calumenin-SAP interaction by the surface plasmon resonance technique. The findings indicate that calumenin may participate...... in the immunological defense system and could be involved in the pathological process of amyloidosis that leads to formation of amyloid deposits seen in different types of tissues. Udgivelsesdato: 2000-Jan-14...

  8. ARF6-dependent regulation of P2Y receptor traffic and function in human platelets.

    Science.gov (United States)

    Kanamarlapudi, Venkateswarlu; Owens, Sian E; Saha, Keya; Pope, Robert J; Mundell, Stuart J

    2012-01-01

    Adenosine diphosphate (ADP) is a critical regulator of platelet activation, mediating its actions through two G protein-coupled receptors, the P2Y(1) and P2Y(12) purinoceptors. Recently, we demonstrated that P2Y(1) and P2Y(12) purinoceptor activities are rapidly and reversibly modulated in human platelets, revealing that the underlying mechanism requires receptor internalization and subsequent trafficking as an essential part of this process. In this study we investigated the role of the small GTP-binding protein ADP ribosylation factor 6 (ARF6) in the internalization and function of P2Y(1) and P2Y(12) purinoceptors in human platelets. ARF6 has been implicated in the internalization of a number of GPCRs, although its precise molecular mechanism in this process remains unclear. In this study we show that activation of either P2Y(1) or P2Y(12) purinoceptors can stimulate ARF6 activity. Further blockade of ARF6 function either in cell lines or human platelets blocks P2Y purinoceptor internalization. This blockade of receptor internalization attenuates receptor resensitization. Furthermore, we demonstrate that Nm23-H1, a nucleoside diphosphate (NDP) kinase regulated by ARF6 which facilitates dynamin-dependent fission of coated vesicles during endocytosis, is also required for P2Y purinoceptor internalization. These data describe a novel function of ARF6 in the internalization of P2Y purinoceptors and demonstrate the integral importance of this small GTPase upon platelet ADP receptor function.

  9. ARF6-dependent regulation of P2Y receptor traffic and function in human platelets.

    Directory of Open Access Journals (Sweden)

    Venkateswarlu Kanamarlapudi

    Full Text Available Adenosine diphosphate (ADP is a critical regulator of platelet activation, mediating its actions through two G protein-coupled receptors, the P2Y(1 and P2Y(12 purinoceptors. Recently, we demonstrated that P2Y(1 and P2Y(12 purinoceptor activities are rapidly and reversibly modulated in human platelets, revealing that the underlying mechanism requires receptor internalization and subsequent trafficking as an essential part of this process. In this study we investigated the role of the small GTP-binding protein ADP ribosylation factor 6 (ARF6 in the internalization and function of P2Y(1 and P2Y(12 purinoceptors in human platelets. ARF6 has been implicated in the internalization of a number of GPCRs, although its precise molecular mechanism in this process remains unclear. In this study we show that activation of either P2Y(1 or P2Y(12 purinoceptors can stimulate ARF6 activity. Further blockade of ARF6 function either in cell lines or human platelets blocks P2Y purinoceptor internalization. This blockade of receptor internalization attenuates receptor resensitization. Furthermore, we demonstrate that Nm23-H1, a nucleoside diphosphate (NDP kinase regulated by ARF6 which facilitates dynamin-dependent fission of coated vesicles during endocytosis, is also required for P2Y purinoceptor internalization. These data describe a novel function of ARF6 in the internalization of P2Y purinoceptors and demonstrate the integral importance of this small GTPase upon platelet ADP receptor function.

  10. ERP to chess stimuli reveal expert-novice differences in the amplitudes of N2 and P3 components.

    Science.gov (United States)

    Wright, Michael J; Gobet, Fernand; Chassy, Philippe; Ramchandani, Payal Nanik

    2013-10-01

    ERP experiments were conducted to analyze the underlying neural events when chess players make simple judgments of a board position. Fourteen expert players and 14 age-matched novices viewed, for each of four tasks, 128 unique positions on a mini (4 × 4) chess board each presented for 0.5 s. The tasks were to respond: (a) if white king was in check, (b) if black knight was present, (c) if white king was not in check, and (d) if no black knight was present. Experts showed an enhanced N2 with check targets and a larger P3 with knight targets, relative to novices. Expert-novice differences in posterior N2 began as early as 240 ms on check-related searches. Results were consistent with the view that prolonged N2 components reflect matching of current perceptual input to memory, and thus are sensitive to experts' superior pattern recognition and memory retrieval of chunks. Copyright © 2013 Society for Psychophysiological Research.

  11. Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma.

    Science.gov (United States)

    Donson, Andrew M; Apps, John; Griesinger, Andrea M; Amani, Vladimir; Witt, Davis A; Anderson, Richard C E; Niazi, Toba N; Grant, Gerald; Souweidane, Mark; Johnston, James M; Jackson, Eric M; Kleinschmidt-DeMasters, Bette K; Handler, Michael H; Tan, Aik-Choon; Gore, Lia; Virasami, Alex; Gonzalez-Meljem, Jose Mario; Jacques, Thomas S; Martinez-Barbera, Juan Pedro; Foreman, Nicholas K; Hankinson, Todd C

    2017-09-01

    Pediatric adamantinomatous craniopharyngioma (ACP) is a highly solid and cystic tumor, often causing substantial damage to critical neuroendocrine structures such as the hypothalamus, pituitary gland, and optic apparatus. Paracrine signaling mechanisms driving tumor behavior have been hypothesized, with IL-6R overexpression identified as a potential therapeutic target. To identify potential novel therapies, we characterized inflammatory and immunomodulatory factors in ACP cyst fluid and solid tumor components. Cytometric bead analysis revealed a highly pro-inflammatory cytokine pattern in fluid from ACP compared to fluids from another cystic pediatric brain tumor, pilocytic astrocytoma. Cytokines and chemokines with particularly elevated concentrations in ACPs were IL-6, CXCL1 (GRO), CXCL8 (IL-8) and the immunosuppressive cytokine IL-10. These data were concordant with solid tumor compartment transcriptomic data from a larger cohort of ACPs, other pediatric brain tumors and normal brain. The majority of receptors for these cytokines and chemokines were also over-expressed in ACPs. In addition to IL-10, the established immunosuppressive factor IDO-1 was overexpressed by ACPs at the mRNA and protein levels. These data indicate that ACP cyst fluids and solid tumor components are characterized by an inflammatory cytokine and chemokine expression pattern. Further study regarding selective cytokine blockade may inform novel therapeutic interventions. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  12. Hypoxia-induced invadopodia formation involves activation of NHE-1 by the p90 ribosomal S6 kinase (p90RSK.

    Directory of Open Access Journals (Sweden)

    Fabrice Lucien

    Full Text Available The hypoxic and acidic microenvironments in tumors are strongly associated with malignant progression and metastasis, and have thus become a central issue in tumor physiology and cancer treatment. Despite this, the molecular links between acidic pH- and hypoxia-mediated cell invasion/metastasis remain mostly unresolved. One of the mechanisms that tumor cells use for tissue invasion is the generation of invadopodia, which are actin-rich invasive plasma membrane protrusions that degrade the extracellular matrix. Here, we show that hypoxia stimulates the formation of invadopodia as well as the invasive ability of cancer cells. Inhibition or shRNA-based depletion of the Na(+/H(+ exchanger NHE-1, along with intracellular pH monitoring by live-cell imaging, revealed that invadopodia formation is associated with alterations in cellular pH homeostasis, an event that involves activation of the Na(+/H(+ exchange rate by NHE-1. Further characterization indicates that hypoxia triggered the activation of the p90 ribosomal S6 kinase (p90 RSK, which resulted in invadopodia formation and site-specific phosphorylation and activation of NHE-1. This study reveals an unsuspected role of p90RSK in tumor cell invasion and establishes p90RS kinase as a link between hypoxia and the acidic microenvironment of tumors.

  13. Synthesis and crystal structure of Bi6.4Pb0.6P2O15.2

    International Nuclear Information System (INIS)

    Arumugam, N.; Lynch, V.; Steinfink, H.

    2007-01-01

    Bi 6.4 Pb 0.6 P 2 O 15.2 is a polymorph of structures with the general stoichiometry Bi 6+x M 1-x P 2 O 15+y . However, unlike previously published structures that consist of layers formed by edge sharing OBi 4 tetrahedra bridged by PO 4 and TO 6 (T=transition metal) tetrahedra and octahedra the title compound's structure is more complex. It is monoclinic, C2, a=19.4698(4) A, b=11.3692(3) A, c=16.3809(5) A, β=101.167(1) o , Z=10. Single-crystal X-ray diffraction data were refined by least squares on F 2 converging to R 1 =0.0387, wR 2 =0.0836 for 7023 intensities. The crystal twins by mirror reflection across (001) as the twin plane and twin component 1 equals 0.74(1). Oxygen ions are in tetrahedral coordination to four metal ions and the O(BiPb) 4 units share corners to form layers that are part of the three-dimensional framework. Eight oxygen ions form a cube around the two crystallographically independent Pb ions. Pb-O bond lengths vary from 2.265(14) to 2.869(14) A. Pairs of such cubes share an edge to form a Pb 3 O 20 unit. The two oxygen ions from the unshared edges are part of irregular Bi polyhedra. Other oxygen ions of Bi polyhedra are part only of O(BiPb) 4 units, and some oxygen ions of the polyhedra are also part of PO 4 tetrahedra. One, two, three and or four PO 4 moieties are connected to the Bi polyhedra. Bi-O bond lengths ≤3.1 A vary from 2.090(12) to 3.07(3) A. The articulations of Pb cubes, Bi polyhedra and PO 4 tetrahedra link into the three-dimensional structure. - Graphical abstract: View of the structure of Bi 6.4 Pb 0.6 P 2 O 15.2 parallel to the b-axis

  14. Dose rates modeling of pressurized water reactor primary loop components with SCALE6.0

    International Nuclear Information System (INIS)

    Matijević, Mario; Pevec, Dubravko; Trontl, Krešimir

    2015-01-01

    Highlights: • Shielding analysis of the typical PWR primary loop components was performed. • FW-CADIS methodology was thoroughly investigated using SCALE6.0 code package. • Versatile ability of SCALE6.0/FW-CADIS for deep penetration models was proved. • The adjoint source with focus on specific material can improve MC modeling. - Abstract: The SCALE6.0 simulation model of a typical PWR primary loop components for effective dose rates calculation based on hybrid deterministic–stochastic methodology was created. The criticality sequence CSAS6/KENO-VI of the SCALE6.0 code package, which includes KENO-VI Monte Carlo code, was used for criticality calculations, while neutron and gamma dose rates distributions were determined by MAVRIC/Monaco shielding sequence. A detailed model of a combinatorial geometry, materials and characteristics of a generic two loop PWR facility is based on best available input data. The sources of ionizing radiation in PWR primary loop components included neutrons and photons originating from critical core and photons from activated coolant in two primary loops. Detailed calculations of the reactor pressure vessel and the upper reactor head have been performed. The efficiency of particle transport for obtaining global Monte Carlo dose rates was further examined and quantified with a flexible adjoint source positioning in phase-space. It was demonstrated that generation of an accurate importance map (VR parameters) is a paramount step which enabled obtaining Monaco dose rates with fairly uniform uncertainties. Computer memory consumption by the S N part of hybrid methodology represents main obstacle when using meshes with large number of cells together with high S N /P N parameters. Detailed voxelization (homogenization) process in Denovo together with high S N /P N parameters is essential for precise VR parameters generation which will result in optimized MC distributions. Shielding calculations were also performed for the reduced PWR

  15. Contrasting Inducible Knockdown of the Auxiliary PTEX Component PTEX88 in P. falciparum and P. berghei Unmasks a Role in Parasite Virulence.

    Directory of Open Access Journals (Sweden)

    Scott A Chisholm

    Full Text Available Pathogenesis of malaria infections is linked to remodeling of erythrocytes, a process dependent on the trafficking of hundreds of parasite-derived proteins into the host erythrocyte. Recent studies have demonstrated that the Plasmodium translocon of exported proteins (PTEX serves as the central gateway for trafficking of these proteins, as inducible knockdown of the core PTEX constituents blocked the trafficking of all classes of cargo into the erythrocyte. However, the role of the auxiliary component PTEX88 in protein export remains less clear. Here we have used inducible knockdown technologies in P. falciparum and P. berghei to assess the role of PTEX88 in parasite development and protein export, which reveal that the in vivo growth of PTEX88-deficient parasites is hindered. Interestingly, we were unable to link this observation to a general defect in export of a variety of known parasite proteins, suggesting that PTEX88 functions in a different fashion to the core PTEX components. Strikingly, PTEX88-deficient P. berghei were incapable of causing cerebral malaria despite a robust pro-inflammatory response from the host. These parasites also exhibited a reduced ability to sequester in peripheral tissues and were removed more readily from the circulation by the spleen. In keeping with these findings, PTEX88-deficient P. falciparum-infected erythrocytes displayed reduced binding to the endothelial cell receptor, CD36. This suggests that PTEX88 likely plays a specific direct or indirect role in mediating parasite sequestration rather than making a universal contribution to the trafficking of all exported proteins.

  16. The Cytochrome P450 gene CYP6P12 confers pyrethroid resistance in kdr-free Malaysian populations of the dengue vector Aedes albopictus.

    Science.gov (United States)

    Ishak, Intan H; Riveron, Jacob M; Ibrahim, Sulaiman S; Stott, Rob; Longbottom, Joshua; Irving, Helen; Wondji, Charles S

    2016-04-20

    Control of Aedes albopictus, major dengue and chikungunya vector, is threatened by growing cases of insecticide resistance. The mechanisms driving this resistance remain poorly characterised. This study investigated the molecular basis of insecticide resistance in Malaysian populations of Ae. albopictus. Microarray-based transcription profiling revealed that metabolic resistance (cytochrome P450 up-regulation) and possibly a reduced penetration mechanism (consistent over-expression of cuticular protein genes) were associated with pyrethroid resistance. CYP6P12 over-expression was strongly associated with pyrethroid resistance whereas CYP6N3 was rather consistently over-expressed across carbamate and DDT resistant populations. Other detoxification genes also up-regulated in permethrin resistant mosquitoes included a glucuronosyltransferase (AAEL014279-RA) and the glutathione-S transferases GSTS1 and GSTT3. Functional analyses further supported that CYP6P12 contributes to pyrethroid resistance in Ae. albopictus as transgenic expression of CYP6P12 in Drosophila was sufficient to confer pyrethroid resistance in these flies. Furthermore, molecular docking simulations predicted CYP6P12 possessing enzymatic activity towards pyrethroids. Patterns of polymorphism suggested early sign of selection acting on CYP6P12 but not on CYP6N3. The major role played by P450 in the absence of kdr mutations suggests that addition of the synergist PBO to pyrethroids could improve the efficacy of this insecticide class and overcome resistance in field populations of Ae. albopictus.

  17. Cyclic di-GMP is essential for the survival of the lyme disease spirochete in ticks.

    Directory of Open Access Journals (Sweden)

    Ming He

    2011-06-01

    Full Text Available Cyclic dimeric GMP (c-di-GMP is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzootic cycle of the Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the diguanylate cyclase gene (rrp1, which is responsible for c-di-GMP synthesis. To determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1-deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious in the mammalian host but cannot survive in the tick vector. Microarray analyses revealed that expression of a four-gene operon involved in glycerol transport and metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1. In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol as the carbon source (BSK-glycerol. To determine the contribution of the glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo, the glp mutant is also infectious in mice but has reduced survival in ticks. Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully rescues the growth defect in BSK-glycerol medium and partially restores survival of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch in B. burgdorferi and plays a vital role in the tick part of the spirochetal enzootic cycle. This work provides the first evidence that c-di-GMP is essential for a pathogen's survival in its vector host.

  18. Revealing the effect of 6-gingerol, 6-shogaol and curcumin on mPGES-1, GSK-3β and β-catenin pathway in A549 cell line.

    Science.gov (United States)

    Eren, Demirpolat; Betul, Yerer Mukerrem

    2016-10-25

    In our study, anticancer effects of 6-gingerol, 6-shogaol from ginger and curcumin from turmeric were investigated and the results were compared with each other. We aimed to reveal their effects on microsomal prostaglandine E2 synthase 1 (mPGES-1) which is related with cancer progression and inflammation as well as β-catenin and glycogen synthase kinase 3β (GSK-3β) that are the main components of Wnt/GSK3 pathway. As it is known activation of GSK-3β and high levels of mPGES-1 pathway leads to cell proliferation and aggravates cancer progression. Therefore both of them are potential targets for cancer therapy. 6-shogaol and 6-gingerol' s effect on this pathway is not known very well up to now while curcumin that is known as an mPGES-1 inhibitor has anticancer properties via this pathway and many other pathways. Besides being in Zingiberaceae family, ginger's 6-gingerol and 6-shogaol have a molecular similarity with turmeric's curcumin. In our study we investigated their effects using a popular non small lung cancer cell line named A549 which expresses mPGES-1 and has active GSK3β pathway. IL-1β was used for inducing mPGES-1 and enabling the cancer characteristics such as cell proliferation. So compounds that inactivates or decreases the level of these components might be potential anticancer agents. A549 cells were incubated with interleukin 1β (IL-1β) for 24 h in order to maintain mPGES-1 enzyme induction. Experiments were performed both on IL-1β and non-IL-1β group. Real time cell analysis was performed to determine the cytotoxicity. Samples for western blotting and RT-PCR were collected after 24 h incubation with compounds to determine the amount of mPGES-1, GSK-3β, p-GSK-3β, β-catenin protein and mRNA. PGE2 which is the end product of mPGES-1 was measured by using ELISA kit. As a result of cell profile assay, cells exposed to IL-1β proliferate faster than non-IL-1β ones. This shows that induced mPGES-1 might play a role through GSK3β pathway

  19. The Thermal-hydraulic Analysis for the Aging Effect of the Component in CANDU-6 Reactor

    International Nuclear Information System (INIS)

    Bae, Jun Ho; Jung, Jong Yeob

    2014-01-01

    CANDU reactor consists of a lot of components, including pressure tube, reactor pump, steam generator, feeder pipe, and so on. These components become to have the aging characteristics as the reactor operates for a long time. The aging phenomena of these components lead to the change of operating parameters, and it finally results to the decrease of the operating safety margin. Actually, due to the aging characteristics of components, CANDU reactor power plant has the operating license for the duration of 30 years and the plant regularly check the plant operating state in the overhaul period. As the reactor experiences the aging, the reactor operators should reduce the reactor power level in order to keep the minimum safety margin, and it results to the deficit of economical profit. Therefore, in order to establish the safety margin for the aged reactor, the aging characteristics for components should be analyzed and the effect of aging of components on the operating parameter should be studied. In this study, the aging characteristics of components are analyzed and revealed how the aging of components affects to the operating parameter by using NUCIRC code. Finally, by scrutinizing the effect of operating parameter on the operating safety margin, the effect of aging of components on the safety margin has been revealed

  20. The tumor suppressor SHIP1 colocalizes in nucleolar cavities with p53 and components of PML nuclear bodies.

    Science.gov (United States)

    Ehm, Patrick; Nalaskowski, Marcus M; Wundenberg, Torsten; Jücker, Manfred

    2015-01-01

    The inositol 5-phosphatase SHIP1 is a negative regulator of signaling processes in haematopoietic cells. By converting PI(3,4,5)P3 to PtdIns(3,4)P2 at the plasma membrane, SHIP1 modifies PI3-kinase mediated signaling. We have recently demonstrated that SHIP1 is a nucleo-cytoplasmic shuttling protein and SHIP1 nuclear puncta partially colocalize with FLASH, a component of nuclear bodies. In this study, we demonstrate that endogenous SHIP1 localizes to intranucleolar regions of both normal and leukemic haematopoietic cells. In addition, we report that ectopically expressed SHIP1 accumulates in nucleolar cavities and colocalizes with the tumor suppressor protein p53 and components of PML nuclear bodies (e.g. SP100, SUMO-1 and CK2). Moreover, SHIP1 also colocalizes in nucleolar cavities with components of the ubiquitin-proteasome pathway. By using confocal microscopy data, we generated 3D-models revealing the enormous extent of the SHIP1 aggresomes in the nucleolus. Furthermore, treatment of cells with the proteasome inhibitor MG132 causes an enlargement of nucleolar SHIP1 containing structures. Unexpectedly, this accumulation can be partially prevented by treatment with the inhibitor of nuclear protein export Leptomycin B. In recent years, several proteins aggregating in nucleolar cavities were shown to be key factors of neurodegenerative diseases and cancerogenesis. Our findings support current relevance of nuclear localized SHIP1.

  1. Laryngopharyngeal reflux and herpes simplex virus type 2 are possible risk factors for adult-onset recurrent respiratory papillomatosis (prospective case-control study).

    Science.gov (United States)

    Formánek, M; Jančatová, D; Komínek, P; Matoušek, P; Zeleník, K

    2017-06-01

    The human papillomavirus (HPV) causes recurrent respiratory papillomatosis (RRP). Although HPV prevalence is high, the incidence of papillomatosis is low. Thus, factors other than HPV infection probably contribute to RRP. This study investigated whether patients with papillomatosis are more often infected with herpes simplex virus type 2 and chlamydia trachomatis (ChT) and whether laryngopharyngeal reflux (LPR) occurs in this group of patients more often. Prospective case-control study. Department of Otorhinolaryngology of University Hospital. The study included 20 patients with adult-onset RRP and 20 adult patients with vocal cord cyst and no pathology of laryngeal mucosa (control group). Immunohistochemical analysis of pepsin, HPV, herpes simplex virus type 2 and ChT was performed in biopsy specimens of laryngeal papillomas and of healthy laryngeal mucosa (control group) obtained from medial part of removed vocal cord cyst during microlaryngoscopy procedures. Pathologic LPR (pepsin in tissue) was diagnosed in 8/20 (40.0%) patients with papillomatosis and in 0/20 control patients (P = .003). Herpes simplex virus type 2 was present in 9/20 (45.0%) patients with papillomatosis and in 0/20 control patients (P = .001). Five specimens were positive for both pepsin and herpes simplex virus type 2. No samples were positive for ChT. There were no significant differences between groups for age, body mass index, diabetes mellitus and gastrooesophageal reflux disease. Tobacco exposure was not more frequent in RRP group either (P = .01). Results show that LPR and herpes simplex virus type 2 are significantly more often present in patients with RRP. LPR and herpes simplex virus type 2 might activate latent HPV infection and thereby be possible risk factors for RRP. © 2016 John Wiley & Sons Ltd.

  2. Purine receptor P2Y_6 mediates cellular response to γ-ray-induced DNA damage

    International Nuclear Information System (INIS)

    Ide, Shunta; Nishimaki, Naoko; Tsukimoto, Mitsutoshi; Kojima, Shuji

    2014-01-01

    We previously showed that nucleotide P2 receptor agonists such as ATP and UTP amplify γ-ray-induced focus formation of phosphorylated histone H2A variant H2AX (γH2AX), which is considered to be an indicator of DNA damage so far, by activating purine P2Y_6 and P2Y_1_2 receptors. Therefore, we hypothesized that these P2 receptors play a role in inducing the repair response to γ-ray-induced DNA damage. In the present study, we tested this idea by using human lung cancer A549 cells. First, reverse-transcription polymerase chain reaction (RT-PCR) showed that P2Y_6 receptor is highly expressed in A549 cells, but P2Y_1_2 receptor is only weakly expressed. Next, colony formation assay revealed that P2Y_6 receptor antagonist MRS2578 markedly reduced the survival rate of γ-ray-exposed A549 cells. The survival rate was also significantly reduced in P2Y_6-knock-down cells, compared with scramble siRNA-transfected cells. Since it has reported that phosphorylation of ERK1/2 after activation of EGFR via P2Y_6 and P2Y_1_2 receptors is involved in the repair response to γ-ray-induced DNA damage, we next examined whether γ-ray-induced phosphorylation of ERK1/2 was also inhibited by MRS2578 in A549 cells. We found that it was. Taken together, these findings indicate that purinergic signaling through P2Y_6 receptor, followed by ERK1/2 activation, promotes the cellular repair response to γ-ray-induced DNA damage. (author)

  3. Localization of nuclear retained mRNAs in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Thomsen, Rune; Libri, Domenico; Boulay, Jocelyne

    2003-01-01

    site of transcription, and known S. cerevisiae nuclear structures such as the nucleolus and the nucleolar body. Our results show that retained SSA4 RNA localizes to an area in close proximity to the SSA4 locus. On deletion of Rrp6p and release from the genomic locus, heat shock mRNAs produced...

  4. Design, synthesis and in vitro evaluation on glucosamine-6P synthase of aromatic analogs of 2-Aminohexitols-6P

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Danielle F.; Alves, Ricardo J., E-mail: ricardodylan@farmacia.ufmg.b [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Farmacia; Roux, Celine; Durand, Philippe; Iorga, Bogdan; Badet-Denisot, Marie A.; Badet, Bernard [Centre National de la Recherche Scientifique (CNRS), Gif-sur-Yvette (France). Inst. de Chimie des Substances Naturelles

    2010-07-01

    The aminosugars are very important structural components of bacterial and fungi cell walls. Glucosamine-6-phosphate synthase (GlmS), which catalyses the first step of the aminosugar biosynthetic pathway i.e. the formation of D-glucosamine-6-phosphate from D-fructose-6-phosphate, is therefore an interesting target in the fight against microorganisms. In this work is described the synthesis of aromatic analogs of 2-amino-2-deoxy-D-glucitol-6-phosphate (ADGP) and its epimer 2-amino-2-deoxy-D-manitol-6-phosphate (ADMP), two important inhibitors of GlmS. The aromatic analogs displayed modest inhibitory activity against GlmS, with IC{sub 50} in the mmol L{sup -1} range. (author)

  5. Comparative biomarker expression and RNA integrity in biospecimens derived from radical retropubic and robot-assisted laparoscopic prostatectomies.

    Science.gov (United States)

    Ricciardelli, Carmela; Bianco-Miotto, Tina; Jindal, Shalini; Dodd, Thomas J; Cohen, Penelope A; Marshall, Villis R; Sutherland, Peter D; Samaratunga, Hemamali; Kench, James G; Dong, Ying; Wang, Hong; Clements, Judith A; Risbridger, Gail P; Sutherland, Robert L; Tilley, Wayne D; Horsfall, David J

    2010-07-01

    Knowledge of preanalytic conditions that biospecimens are subjected to is critically important because novel surgical procedures, tissue sampling, handling, and storage might affect biomarker expression or invalidate tissue samples as analytes for some technologies. We investigated differences in RNA quality, gene expression by quantitative real-time PCR, and immunoreactive protein expression of selected prostate cancer biomarkers between tissues from retropubic radical prostatectomy (RRP) and robot-assisted laparoscopic prostatectomy (RALP). Sections of tissue microarray of 23 RALP and 22 RRP samples were stained with antibodies to androgen receptor (AR) and prostate-specific antigen (PSA) as intersite controls, and 14 other candidate biomarkers of research interest to three laboratories within the Australian Prostate Cancer BioResource tissue banking network. Quantitative real-time PCR was done for AR, PSA (KLK3), KLK2, KLK4, and HIF1A on RNA extracted from five RALP and five RRP frozen tissue cores. No histologic differences were observed between RALP and RRP tissue. Biomarker staining grouped these samples into those with increased (PSA, CK8/18, CKHMW, KLK4), decreased (KLK2, KLK14), or no change in expression (AR, ghrelin, Ki67, PCNA, VEGF-C, PAR2, YB1, p63, versican, and chondroitin 0-sulfate) in RALP compared with RRP tissue. No difference in RNA quality or gene expression was detected between RALP and RRP tissue. Changes in biomarker expression between RALP and RRP tissue exist at the immunoreactive protein level, but the etiology is unclear. Future studies should account for changes in biomarker expression when using RALP tissues, and mixed cohorts of RALP and RRP tissue should be avoided.

  6. Glutamic Acid Residues in HIV-1 p6 Regulate Virus Budding and Membrane Association of Gag.

    Science.gov (United States)

    Friedrich, Melanie; Setz, Christian; Hahn, Friedrich; Matthaei, Alina; Fraedrich, Kirsten; Rauch, Pia; Henklein, Petra; Traxdorf, Maximilian; Fossen, Torgils; Schubert, Ulrich

    2016-04-25

    The HIV-1 Gag p6 protein regulates the final abscission step of nascent virions from the cell membrane by the action of its two late (L-) domains, which recruit Tsg101 and ALIX, components of the ESCRT system. Even though p6 consists of only 52 amino acids, it is encoded by one of the most polymorphic regions of the HIV-1 gag gene and undergoes various posttranslational modifications including sumoylation, ubiquitination, and phosphorylation. In addition, it mediates the incorporation of the HIV-1 accessory protein Vpr into budding virions. Despite its small size, p6 exhibits an unusually high charge density. In this study, we show that mutation of the conserved glutamic acids within p6 increases the membrane association of Pr55 Gag followed by enhanced polyubiquitination and MHC-I antigen presentation of Gag-derived epitopes, possibly due to prolonged exposure to membrane bound E3 ligases. The replication capacity of the total glutamic acid mutant E0A was almost completely impaired, which was accompanied by defective virus release that could not be rescued by ALIX overexpression. Altogether, our data indicate that the glutamic acids within p6 contribute to the late steps of viral replication and may contribute to the interaction of Gag with the plasma membrane.

  7. Control of enteric pathogens in ready-to-eat vegetable crops in organic and 'low input' production systems: a HACCP-based approach.

    Science.gov (United States)

    Leifert, C; Ball, K; Volakakis, N; Cooper, J M

    2008-10-01

    Risks from pathogens such as Salmonella, Yersinia, Campylobacter and Escherichia coli O157 have been identified as a particular concern for organic and 'low input' food production systems that rely on livestock manure as a nutrient source. Current data do not allow any solid conclusions to be drawn about the level of this risk, relative to conventional production systems. This review describes six Risk Reduction Points (RRPs) where risks from enteric pathogens can be reduced in ready-to-eat vegetables. Changes can be made to animal husbandry practices (RRP1) to reduce inoculum levels in manure. Outdoor livestock management (RRP2) can be optimized to eliminate the risk of faecal material entering irrigation water. Manure storage and processing (RRP3), soil management practices (RRP4) and timing of manure application (RRP5), can be adjusted to reduce the survival of pathogens originating from manure. During irrigation (RRP6), pathogen risks can be reduced by choosing a clean water source and minimizing the chances of faecal material splashing on to the crop. Although preventive measures at these RRPs can minimize enteric pathogen risk, zero risk can never be obtained for raw ready-to-eat vegetables. Good food hygiene practices at home are essential to reduce the incidence of food-borne illnesses.

  8. Ultrathin regioregular poly(3-hexyl thiophene) field-effect transistors

    DEFF Research Database (Denmark)

    Sandberg, H.G.O.; Frey, G.L.; Shkunov, M.N.

    2002-01-01

    Ultrathin films of regioregular poly(3-hexyl thiophene) (RR-P3HT) were deposited through a dip-coating technique and utilized as the semiconducting film in field-effect transistors (FETs). Proper selection of the substrate and solution concentration enabled the growth of a monolayer-thick RR-P3HT...... film. Atomic force microscopy (AFM), U-V-vis absorption spectroscopy, X-ray reflectivity, and grazing incidence diffraction were used to study the growth mechanism, thickness and orientation of self-organized monolayer thick RR-P3HT films on SiO2 surfaces. Films were found to adopt a Stranski......-Krastanov-type growth mode with formation of a very stable first monolayer. X-ray measurements show that the direction of pi-stacking in the films (the (010) direction) is parallel to the substrate, which is the preferred orientation for high field-effect carrier mobilities. The field-effect mobilities in all ultrathin...

  9. Long Lived Photoexcitation Dynamics in π-Conjugated Polymer/PbS Quantum Dot Blended Films for Photovoltaic Application

    Directory of Open Access Journals (Sweden)

    Ruizhi Wang

    2017-08-01

    Full Text Available We used continuous wave photoinduced absorption (PIA spectroscopy to investigate long-lived polarons in a blend of PbS quantum dot and regio-regular poly (3-hexylthiophene (RR-P3HT. The charge transfer from RR-P3HT to PbS as well as from PbS to RR-P3HT were observed after changing the capping ligand of PbS from a long chain molecular to a short one. Therefore, PbS could be used to extend the working spectral range in hybrid solar cells with a proper capping ligand. However, we found that the recombination mechanism in the millisecond time region is dominated by the trap/defects in blended films, while it improves to a bimolecular recombination partially after ligand exchange. Our results suggest that passivating traps of nanocrystals by improving surface ligands will be crucial for relevant solar cell applications.

  10. CW EPR parameters reveal cytochrome P450 ligand binding modes.

    Science.gov (United States)

    Lockart, Molly M; Rodriguez, Carlo A; Atkins, William M; Bowman, Michael K

    2018-06-01

    Cytochrome P450 (CYP) monoxygenses utilize heme cofactors to catalyze oxidation reactions. They play a critical role in metabolism of many classes of drugs, are an attractive target for drug development, and mediate several prominent drug interactions. Many substrates and inhibitors alter the spin state of the ferric heme by displacing the heme's axial water ligand in the resting enzyme to yield a five-coordinate iron complex, or they replace the axial water to yield a nitrogen-ligated six-coordinate iron complex, which are traditionally assigned by UV-vis spectroscopy. However, crystal structures and recent pulsed electron paramagnetic resonance (EPR) studies find a few cases where molecules hydrogen bond to the axial water. The water-bridged drug-H 2 O-heme has UV-vis spectra similar to nitrogen-ligated, six-coordinate complexes, but are closer to "reverse type I" complexes described in older liteature. Here, pulsed and continuous wave (CW) EPR demonstrate that water-bridged complexes are remarkably common among a range of nitrogenous drugs or drug fragments that bind to CYP3A4 or CYP2C9. Principal component analysis reveals a distinct clustering of CW EPR spectral parameters for water-bridged complexes. CW EPR reveals heterogeneous mixtures of ligated states, including multiple directly-coordinated complexes and water-bridged complexes. These results suggest that water-bridged complexes are under-represented in CYP structural databases and can have energies similar to other ligation modes. The data indicates that water-bridged binding modes can be identified and distinguished from directly-coordinated binding by CW EPR. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Reliability Analysis of 6-Component Star Markov Repairable System with Spatial Dependence

    Directory of Open Access Journals (Sweden)

    Liying Wang

    2017-01-01

    Full Text Available Star repairable systems with spatial dependence consist of a center component and several peripheral components. The peripheral components are arranged around the center component, and the performance of each component depends on its spatial “neighbors.” Vector-Markov process is adapted to describe the performance of the system. The state space and transition rate matrix corresponding to the 6-component star Markov repairable system with spatial dependence are presented via probability analysis method. Several reliability indices, such as the availability, the probabilities of visiting the safety, the degradation, the alert, and the failed state sets, are obtained by Laplace transform method and a numerical example is provided to illustrate the results.

  12. A Unique Failure Mechanism in the Nexus 6P Lithium-Ion Battery

    Directory of Open Access Journals (Sweden)

    Saurabh Saxena

    2018-04-01

    Full Text Available Nexus 6P smartphones have been beset by battery drain issues, which have been causing premature shutdown of the phone even when the charge indicator displays a significant remaining runtime. To investigate the premature battery drain issue, two Nexus 6P smartphones (one new and one used were disassembled and their batteries were evaluated using computerized tomography (CT scan analysis, electrical performance (capacity, resistance, and impedance tests, and cycle life capacity fade tests. The “used” smartphone battery delivered only 20% of the rated capacity when tested in a first capacity cycle and then 15% of the rated capacity in a second cycle. The new smartphone battery exceeded the rated capacity when first taken out of the box, but exhibited an accelerated capacity fade under C/2 rate cycling and decreased to 10% of its initial capacity in just 50 cycles. The CT scan results revealed the presence of contaminant materials inside the used battery, raising questions about the quality of the manufacturing process.

  13. Footprinting analysis of interactions between the largest eukaryotic RNase P/MRP protein Pop1 and RNase P/MRP RNA components.

    Science.gov (United States)

    Fagerlund, Robert D; Perederina, Anna; Berezin, Igor; Krasilnikov, Andrey S

    2015-09-01

    Ribonuclease (RNase) P and RNase MRP are closely related catalytic ribonucleoproteins involved in the metabolism of a wide range of RNA molecules, including tRNA, rRNA, and some mRNAs. The catalytic RNA component of eukaryotic RNase P retains the core elements of the bacterial RNase P ribozyme; however, the peripheral RNA elements responsible for the stabilization of the global architecture are largely absent in the eukaryotic enzyme. At the same time, the protein makeup of eukaryotic RNase P is considerably more complex than that of the bacterial RNase P. RNase MRP, an essential and ubiquitous eukaryotic enzyme, has a structural organization resembling that of eukaryotic RNase P, and the two enzymes share most of their protein components. Here, we present the results of the analysis of interactions between the largest protein component of yeast RNases P/MRP, Pop1, and the RNA moieties of the enzymes, discuss structural implications of the results, and suggest that Pop1 plays the role of a scaffold for the stabilization of the global architecture of eukaryotic RNase P RNA, substituting for the network of RNA-RNA tertiary interactions that maintain the global RNA structure in bacterial RNase P. © 2015 Fagerlund et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  14. Raman chemical mapping reveals site of action of HIV protease inhibitors in HPV16 E6 expressing cervical carcinoma cells.

    Science.gov (United States)

    Kim, Dong-Hyun; Jarvis, Roger M; Allwood, J William; Batman, Gavin; Moore, Rowan E; Marsden-Edwards, Emma; Hampson, Lynne; Hampson, Ian N; Goodacre, Royston

    2010-12-01

    It has been shown that the HIV protease inhibitors indinavir and lopinavir may have activity against the human papilloma virus (HPV) type 16 inhibiting HPV E6-mediated proteasomal degradation of p53 in cultured cervical carcinoma cells. However, their mode and site of action is unknown. HPV-negative C33A cervical carcinoma cells and the same cells stably transfected with E6 (C33AE6) were exposed to indinavir and lopinavir at concentrations of 1 mM and 30 μM, respectively. The intracellular distribution of metabolites and metabolic changes induced by these treatments were investigated by Raman microspectroscopic imaging combined with the analysis of cell fractionation products by liquid chromatography-mass spectrometry (LC-MS). A uniform cellular distribution of proteins was found in drug-treated cells irrespective of cell type. Indinavir was observed to co-localise with nucleic acid in the nucleus, but only in E6 expressing cells. Principal components analysis (PCA) score maps generated on the full Raman hypercube and the corresponding PCA loadings plots revealed that the majority of metabolic variations influenced by the drug exposure within the cells were associated with changes in nucleic acids. Analysis of cell fractionation products by LC-MS confirmed that the level of indinavir in nuclear extracts was approximately eight-fold greater than in the cytoplasm. These data demonstrate that indinavir undergoes enhanced nuclear accumulation in E6-expressing cells, which suggests that this is the most likely site of action for this compound against HPV.

  15. Urinary incontinence and voiding dysfunction after radical retropubic prostatectomy (prospective urodynamic study).

    Science.gov (United States)

    Majoros, Attila; Bach, Dietmar; Keszthelyi, Attila; Hamvas, Antal; Romics, Imre

    2006-01-01

    During this prospective study we analyzed the effects of radical retropubic prostatectomy (RRP) on bladder and sphincter function by comparing preoperative and postoperative urodynamic data. The aim of the study was to determine the reason for urinary incontinence after RRP and explain why one group of patients will be immediately continent after catheter removal, while others need some time to reach complete continence. Urodynamic examination was performed in 63 patients 3-7 days before and 2 months after surgery. Forty-three (68.2%) and 53 (84.1%) patients regained continence at 2 and 9 months following RRP, respectively. Ten patients (15.9%) were immediately continent after catheter removal. Urodynamic stress incontinence was detected in 18 (28.6%), and detrusor overactivity incontinence in 2 (3.2%) patients 2 months after surgery. The amplitude of preoperative maximal voluntary sphincteric contractions was significantly higher in the postoperative continent group (125 vs. 96.5 cmH(2)O, P continent following catheter removal had no lower urinary tract symptoms (LUTS) and urodynamic abnormality preoperatively, and they had significantly higher preoperative and postoperative maximum urethral closure pressure (at rest and during voluntary sphincter contraction) than those who became continent later on. These data suggest that the main cause of incontinence after RRP is sphincteric weakness. In the continent group, those who became immediately continent had significantly higher maximum urethral closure pressure values at rest and at voluntary sphincteric contraction even before the surgery. Neurourol. Urodynam. (c) 2005 Wiley-Liss, Inc.

  16. The application of iterative transformation factor analysis to resolve multi-component EXAFS spectra of uranium(6) complexes with acetic acid as a function of pH

    International Nuclear Information System (INIS)

    Robberg, A.; Reich, T.

    2002-01-01

    Synchrotron-based EXAFS spectroscopy is a powerful technique to obtain structural information on radionuclide complexes in solution. Depending on the chemical conditions of the samples several radionuclide species can coexist in the solution as is often the case for environmentally related samples. All radionuclide species, which may have different near-neighbour environments, contribute to the measured EXAFS signal. In order to isolate the EXAFS spectra of the individual species (pure spectral components), it is necessary, in a first step, to measure a series of samples where their composition is changed by variation of one physico-chemical parameter (e.g. pH, concentration, etc.). For the spectral decomposition it is necessary that the EXAFS signal change as a function of the chosen physico-chemical parameter. In a second step, the series of EXAFS spectra is analysed with Eigen analysis and Iterative Transformation Factor Analysis (ITFA). As a result of the ITFA one obtains: a) for each sample the relative concentration of the structural distinguishable species and b) their corresponding pure spectral components. From the information obtained in a), one can construct a speciation diagram. The pure spectral components contain the structural information of the individual species, which can be extracted by conventional EXAFS analysis. To evaluate our ITFA algorithm for EXAFS analysis of mixtures, we prepared a series of eight solution samples of 0.05 M uranium(VI) and 1 M acetate (Ac) in the pH range of 0.1 to 4.5. From thermodynamic constants it is known that under these conditions up to four species can occur: uranyl hydrate, and the 1:1, 1:2 and 1:3 complexes of uranyl acetate. The uranium L III -edge EXAFS spectra were measured at room temperature in transmission mode at the Rossendorf Beamline (ROBL) at the ESRF. The average bond length between uranium and the equatorial oxygen atoms (O eq ) increases from 2.40 to 2.46 angstrom with increasing pH. This increase

  17. What Do s- and p-Wave Neutron Average Radiative Widths Reveal

    Energy Technology Data Exchange (ETDEWEB)

    Mughabghab, S.F.

    2010-04-30

    A first observation of two resonance-like structures at mass numbers 92 and 112 in the average capture widths of the p-wave neutron resonances relative to the s-wave component is interpreted in terms of a spin-orbit splitting of the 3p single-particle state into P{sub 3/2} and P{sub 1/2} components at the neutron separation energy. A third structure at about A = 124, which is not correlated with the 3p-wave neutron strength function, is possibly due to the Pygmy Dipole Resonance. Five significant results emerge from this investigation: (i) The strength of the spin-orbit potential of the optical-model is determined as 5.7 {+-} 0.5 MeV, (ii) Non-statistical effects dominate the p-wave neutron-capture in the mass region A = 85 - 130, (iii) The background magnitude of the p-wave average capture-width relative to that of the s-wave is determined as 0.50 {+-} 0.05, which is accounted for quantitatively in tenns of the generalized Fermi liquid model of Mughabghab and Dunford, (iv) The p-wave resonances arc partially decoupled from the giant-dipole resonance (GDR), and (v) Gamma-ray transitions, enhanced over the predictions of the GDR, are observed in the {sup 90}Zr - {sup 98}Mo and Sn-Ba regions.

  18. Case of 7p22.1 Microduplication Detected by Whole Genome Microarray (REVEAL) in Workup of Child Diagnosed with Autism

    OpenAIRE

    Goitia, Veronica; Oquendo, Marcial; Stratton, Robert

    2015-01-01

    Introduction. More than 60 cases of 7p22 duplications and deletions have been reported with over 16 of them occurring without concomitant chromosomal abnormalities. Patient and Methods. We report a 29-month-old male diagnosed with autism. Whole genome chromosome SNP microarray (REVEAL) demonstrated a 1.3?Mb interstitial duplication of 7p22.1 ->p22.1 arr 7p22.1 (5,436,367?6,762,394), the second smallest interstitial 7p duplication reported to date. This interval included 14 OMIM annotated gene...

  19. Modification of nylon-6 with semi-rigid poly (p-diphenyl oxide terephthalamide)

    International Nuclear Information System (INIS)

    Lin, M.F.; Wang, H.H.; Shu, Y.C.

    1994-01-01

    In this study, the flexible nylon-6 was reinforced by the semi-rigid aromatic polyamide, poly (p-diphenyl oxide terephthalamide) (POA), through physical polybending and chemical copolymerization using p-aminophenylacetic acid (P-APA) as a coupling agent. From the DSC measurements, it was shown that Tg of the polyblends was increased with the increase of POA content. The Tg and Tm of multiblock copolyamides were found to be higher than those of polyblends and triblock copolyamides. From the Rheovibron measurements, it was shown that the POA with nylon-6 poy-blends exhibited higher E' and Tg value than that of nylon-6, which increased with the increase of POA content. The Tg and E' values of multiblock copolyamides were higher than those of polyblends triblock copolyamides. Scanning electron microscopy revealed that the polyblends were a dispersed phase structure, although the multiblock copolyamides exhibited a homogeneous texture rather than an aggregated one. From the wide-angle x-ray diffraction pattern, the triblock copolyamides and polyblends had two diffraction peaks, i.e., 2 θ = 20.5 degrees and 24 degrees. However, the multiblock had only one at 2 θ = 20 degrees, which indicates that a different crystal structure of multiblock copolyamides. For the mechanical properties, it was found that the multiblock copolyamides had a more significant reinforcing effect than those of polyblends and triblock copolyamides. 21 refs., 11 figs., 5 tabs

  20. Dis3- and exosome subunit-responsive 3′ mRNA instability elements

    International Nuclear Information System (INIS)

    Kiss, Daniel L.; Hou, Dezhi; Gross, Robert H.; Andrulis, Erik D.

    2012-01-01

    Highlights: ► Successful use of a novel RNA-specific bioinformatic tool, RNA SCOPE. ► Identified novel 3′ UTR cis-acting element that destabilizes a reporter mRNA. ► Show exosome subunits are required for cis-acting element-mediated mRNA instability. ► Define precise sequence requirements of novel cis-acting element. ► Show that microarray-defined exosome subunit-regulated mRNAs have novel element. -- Abstract: Eukaryotic RNA turnover is regulated in part by the exosome, a nuclear and cytoplasmic complex of ribonucleases (RNases) and RNA-binding proteins. The major RNase of the complex is thought to be Dis3, a multi-functional 3′–5′ exoribonuclease and endoribonuclease. Although it is known that Dis3 and core exosome subunits are recruited to transcriptionally active genes and to messenger RNA (mRNA) substrates, this recruitment is thought to occur indirectly. We sought to discover cis-acting elements that recruit Dis3 or other exosome subunits. Using a bioinformatic tool called RNA SCOPE to screen the 3′ untranslated regions of up-regulated transcripts from our published Dis3 depletion-derived transcriptomic data set, we identified several motifs as candidate instability elements. Secondary screening using a luciferase reporter system revealed that one cassette—harboring four elements—destabilized the reporter transcript. RNAi-based depletion of Dis3, Rrp6, Rrp4, Rrp40, or Rrp46 diminished the efficacy of cassette-mediated destabilization. Truncation analysis of the cassette showed that two exosome subunit-sensitive elements (ESSEs) destabilized the reporter. Point-directed mutagenesis of ESSE abrogated the destabilization effect. An examination of the transcriptomic data from exosome subunit depletion-based microarrays revealed that mRNAs with ESSEs are found in every up-regulated mRNA data set but are underrepresented or missing from the down-regulated data sets. Taken together, our findings imply a potentially novel mechanism of m

  1. Genome-wide analysis reveals the vacuolar pH-stat of Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Christopher L Brett

    Full Text Available Protons, the smallest and most ubiquitous of ions, are central to physiological processes. Transmembrane proton gradients drive ATP synthesis, metabolite transport, receptor recycling and vesicle trafficking, while compartmental pH controls enzyme function. Despite this fundamental importance, the mechanisms underlying pH homeostasis are not entirely accounted for in any organelle or organism. We undertook a genome-wide survey of vacuole pH (pH(v in 4,606 single-gene deletion mutants of Saccharomyces cerevisiae under control, acid and alkali stress conditions to reveal the vacuolar pH-stat. Median pH(v (5.27±0.13 was resistant to acid stress (5.28±0.14 but shifted significantly in response to alkali stress (5.83±0.13. Of 107 mutants that displayed aberrant pH(v under more than one external pH condition, functional categories of transporters, membrane biogenesis and trafficking machinery were significantly enriched. Phospholipid flippases, encoded by the family of P4-type ATPases, emerged as pH regulators, as did the yeast ortholog of Niemann Pick Type C protein, implicated in sterol trafficking. An independent genetic screen revealed that correction of pH(v dysregulation in a neo1(ts mutant restored viability whereas cholesterol accumulation in human NPC1(-/- fibroblasts diminished upon treatment with a proton ionophore. Furthermore, while it is established that lumenal pH affects trafficking, this study revealed a reciprocal link with many mutants defective in anterograde pathways being hyperacidic and retrograde pathway mutants with alkaline vacuoles. In these and other examples, pH perturbations emerge as a hitherto unrecognized phenotype that may contribute to the cellular basis of disease and offer potential therapeutic intervention through pH modulation.

  2. Calorimetric and diffractometric evidence for the sequential crystallization of buffer components and the consequential pH swing in frozen solutions.

    Science.gov (United States)

    Sundaramurthi, Prakash; Shalaev, Evgenyi; Suryanarayanan, Raj

    2010-04-15

    Sequential crystallization of succinate buffer components in the frozen solution has been studied by differential scanning calorimetry and X-ray diffractometry (both laboratory and synchrotron sources). The consequential pH shifts were monitored using a low-temperature electrode. When a solution buffered to pH pK(a)(2), the freeze-concentrate pH first decreased and then increased due to the sequential crystallization of the basic (disodium succinate) followed by the acidic (monosodium succinate and succinic acid) buffer components. XRD provided direct evidence of the crystallization events in the frozen buffer solutions, including the formation of disodium succinate hexahydrate [Na(2)(CH(2)COO)(2).6H(2)O]. When the frozen solution was warmed in a differential scanning calorimeter, multiple endotherms attributable to the melting of buffer components and ice were observed. When the frozen solutions were dried under reduced pressure, ice sublimation was followed by dehydration of the crystalline hexahydrate to a poorly crystalline anhydrate. However, crystalline succinic acid and monosodium succinate were retained in the final lyophiles. The pH and the buffer salt concentration of the prelyo solution influenced the crystalline salt content in the final lyophile. The direction and magnitude of the pH shift in the frozen solution depended on both the initial pH and the buffer concentration. In light of the pH-sensitive nature of a significant fraction of pharmaceuticals (especially proteins), extreme care is needed in both the buffer selection and its concentration.

  3. Peculiarities of component interaction in {Gd, Er}-V-Sn Ternary systems at 870 K and crystal structure of RV6Sn6 stannides

    International Nuclear Information System (INIS)

    Romaka, L.; Stadnyk, Yu.; Romaka, V.V.; Demchenko, P.; Stadnyshyn, M.; Konyk, M.

    2011-01-01

    Highlights: → {Gd, Er}-V-Sn ternary systems at 870 K are characterized by formation of stannides with general compositions RV 6 Sn 6 . → Isostructural RV 6 Sn 6 compounds were also found with Y, Dy, Ho, Tm, and Lu. → The crystal structure of RV 6 Sn 6 compounds was determined by powder diffraction method. → Structural analysis showed that RV 6 Sn 6 compounds (R = Gd, Dy-Tm, Lu) are disordered; YV 6 Sn 6 is characterized by structure ordering. - Abstract: The phase equilibria in the Gd-V-Sn and Er-V-Sn ternary systems were studied at 870 K by means of X-ray and metallographic analyses in the whole concentration range. Both Gd-V-Sn and Er-V-Sn systems are characterized by formation of one ternary compound at investigated temperature, with stoichiometry RV 6 Sn 6 (SmMn 6 Sn 6 -type, space group P6/mmm, a = 0.55322(3) nm, c = 0.91949(7) nm for Gd, a = 0.55191(2) nm, c = 0.91869(8) nm for Er). Solubility of the third component in the binary compounds was not observed. Compounds with the SmMn 6 Sn 6 -type were also found with Dy, Ho, Tm, and Lu, while YV 6 Sn 6 compound crystallizes in HfFe 6 Ge 6 structure type. All investigated compounds are the first ternary stannides with rare earth elements and vanadium.

  4. Removal of uranyl ions by p-hexasulfonated calyx[6]arene acid

    Energy Technology Data Exchange (ETDEWEB)

    Popescu, Ioana-Carmen [R and D National Institute for Metals and Radioactive Resources–ICPMRR, B-dul Carol I No.70, Sector 2, Bucharest 020917 (Romania); Petru, Filip [“C.D. Nenitescu” Institute of Organic Chemistry, Splaiul Independentei 202B, Sector 6, Bucharest 71141 (Romania); Humelnicu, Ionel [“Al.I. Cuza” University of Iasi, The Faculty of Chemistry, Bd. Carol-I No. 11, Iasi 700506 (Romania); Mateescu, Marina [National R and D Institute for Chemistry and Petrochemistry, Splaiul Independenţei No. 202, Bucharest 060021 (Romania); Militaru, Ecaterina [R and D National Institute for Metals and Radioactive Resources–ICPMRR, B-dul Carol I No.70, Sector 2, Bucharest 020917 (Romania); Humelnicu, Doina, E-mail: doinah@uaic.ro [“Al.I. Cuza” University of Iasi, The Faculty of Chemistry, Bd. Carol-I No. 11, Iasi 700506 (Romania)

    2014-10-15

    Radioactive pollution is a significant threat for the people’s health. Therefore highly effective radioactive decontamination methods are required. Ion exchange, biotechnologies and phytoremediation in constructed wetlands have been used as radioactive decontamination technologies for uranium contaminated soil and water remediation. Recently, beside those classical methods the calix[n]arenic derivatives’ utilization as radioactive decontaminators has jogged attention. The present work aims to present the preliminary research results of uranyl ion sorption studies on the p-hexasulfonated calyx[6]arenic acid. The effect of temperature, contact time, sorbent amount and uranyl concentration variation on sorption efficiency was investigated. Isotherm models revealed that the sorption process fit better Langmuir isotherm.

  5. Klinische Ergebnisse in der Behandlung der rezidivierenden respiratorischen Papillomatose mit Microdebrider, intraläsionaler Cidofovir-Injektion und Impfung mit Gardasil

    OpenAIRE

    Schäfer, Fabian Axel

    2013-01-01

    Die Rekurrierende Respiratorische Papillomatose (RRP) ist eine seltene Erkrankung, die Kinder, aber auch Erwachsene betrifft. Sie ist charakterisiert durch eine Proliferation benigner Plattenepithel-Papillome innerhalb des Aerodigestiv-Traktes mit dem Larynx als Prädilektionsstelle. Hervorgerufen wird die RRP durch eine orale Infektion mit Humanen Papillomviren (HPV) der Typen 6 oder 11. Bei aggressiven Verlaufsformen, die eine Vielzahl von Papillomabtragungen im Abstand von wenigen Monaten o...

  6. Molecular components in P-wave charmed-strange mesons

    CERN Document Server

    Ortega, Pablo G.

    2016-10-26

    Results obtained by various experiments show that the $D_{s0}^{\\ast}(2317)$ and $D_{s1}(2460)$ mesons are very narrow states located below the $DK$ and $D^{\\ast}K$ thresholds, respectively. This is markedly in contrast with the expectations of naive quark models and heavy quark symmetry. Motivated by a recent lattice study which addresses the mass shifts of the $c\\bar{s}$ ground states with quantum numbers $J^{P}=0^{+}$ ($D_{s0}^{\\ast}(2317)$) and $J^{P}=1^{+}$ ($D_{s1}(2460)$) due to their coupling with $S$-wave $D^{(\\ast)}K$ thresholds, we perform a similar analysis within a nonrelativistic constituent quark model in which quark-antiquark and meson-meson degrees of freedom are incorporated. The quark model has been applied to a wide range of hadronic observables and thus the model parameters are completely constrained. The coupling between quark-antiquark and meson-meson Fock components is done using a modified version of the $^{3}P_{0}$ decay model. We observe that the coupling of the $0^{+}$ $(1^{+})$ mes...

  7. Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53.

    Directory of Open Access Journals (Sweden)

    Kristina Kirschner

    2015-03-01

    Full Text Available The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage and chronically activated (in senescent or pro-apoptotic conditions p53. Compared to the classical 'acute' p53 binding profile, 'chronic' p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory 'p53 hubs' where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the 'lipogenic phenotype', a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms.

  8. Active Components with Inhibitory Activities on IFN-γ/STAT1 and IL-6/STAT3 Signaling Pathways from Caulis Trachelospermi

    Directory of Open Access Journals (Sweden)

    Xiao-Ting Liu

    2014-08-01

    Full Text Available Initial investigation for new active herbal extract with inhibiting activity on JAK/STAT signaling pathway revealed that the extract of Caulis Trachelospermi, which was separated by 80% alcohol extraction and subsequent HP-20 macroporous resin column chromatography, was founded to strongly inhibit IFN-γ-induced STAT1-responsive luciferase activity (IFN-γ/STAT1 with IC50 value of 2.43 μg/mL as well as inhibiting IL-6-induced STAT3-responsive luciferase activity (IL-6/STAT3 with IC50 value of 1.38 μg/mL. Subsequent study on its active components led to the isolation and identification of two new dibenzylbutyrolactone lignans named 4-demethyltraxillaside (1 and nortrachelogenin 4-O-β-d-glucopyranoside (2, together with six known compounds. The lignan compounds 1–4 together with other lignan compounds isolated in previous study were tested the activities on IFN-γ/STAT1 and IL-6/STAT3 pathways. The following result showed that the main components trachelogenin and arctigenin had corresponding activities on IFN-γ/STAT1 pathway with IC50 values of 3.14 μM and 9.46 μM as well as trachelogenin, arctigenin and matairesinol strongly inhibiting IL-6/STAT3 pathway with IC50 values of 3.63 μM, 6.47 μM and 2.92 μM, respectively.

  9. P1 and N170 components distinguish human-like and animal-like makeup stimuli.

    Science.gov (United States)

    Luo, Shuwei; Luo, Wenbo; He, Weiqi; Chen, Xu; Luo, Yuejia

    2013-06-19

    This study used event-related potentials to investigate the sensitivity of P1 and N170 components to human-like and animal-like makeup stimuli, which were derived from pictures of Peking opera characters. As predicted, human-like makeup stimuli elicited larger P1 and N170 amplitudes than did animal-like makeup stimuli. Interestingly, a right hemisphere advantage was observed for human-like but not for animal-like makeup stimuli. Dipole source analyses of 130-200-ms window showed that the bilateral fusiform face area may contribute to the differential sensitivity of the N170 component in response to human-like and animal-like makeup stimuli. The present study suggests that the amplitudes of both the P1 and the N170 are sensitive for the mouth component of face-like stimuli.

  10. Interaction Profiling Identifies the Human Nuclear Exosome Targeting Complex

    DEFF Research Database (Denmark)

    Lubas, Michal Szymon; Christensen, Marianne Skovgaard; Kristiansen, Maiken Søndergaard

    2011-01-01

    from nucleoli, and consistently NEXT is specifically required for the exosomal degradation of promoter upstream transcripts (PROMPTs). We also detect putative homolog TRAMP subunits hTRF4-2 (Trf4p) and ZCCHC7 (Air2p) in hRRP6 and hMTR4 precipitates. However, at least ZCCHC7 function is restricted...... to nucleoli. Our results suggest that human nuclear exosome degradation pathways comprise modules of spatially organized cofactors that diverge from the yeast model....

  11. Anisotropic thermal properties and ferroelectric phase transitions in layered CuInP2S6 and CuInP2Se6 crystals

    Science.gov (United States)

    Liubachko, V.; Shvalya, V.; Oleaga, A.; Salazar, A.; Kohutych, A.; Pogodin, A.; Vysochanskii, Yu. M.

    2017-12-01

    Thermal diffusivity and thermal conductivity have been studied for the layered crystals CuInP2S6, CuInP2Se6 from 30 K to 350 K, showing a relevant thermal anisotropy. Heat is much more efficiently transferred within the layers than perpendicular to them. The ferrielectric transition in CuInP2S6 is proven to be clearly first order while the ferroelectric one in CuInP2Se6 has a weak first order character. The behavior of the thermal conductivity as a function of temperature in the ferroelectric phases shows that heat conduction is phonon driven. Disorder in the paraelectric phases due to hopping motions of Cu ions significantly reduces the thermal conductivity to extremely low values.

  12. Tungsten phosphanylarylthiolato complexes [W{PhP(2-SC6H4)2-kappa3S,S',P} 2] and [W{P(2-SC6H4)3-kappa4S,S',S",P}2]: synthesis, structures and redox chemistry.

    Science.gov (United States)

    Hildebrand, Alexandra; Lönnecke, Peter; Silaghi-Dumitrescu, Luminita; Hey-Hawkins, Evamarie

    2008-09-14

    PhP(2-SHC6H4)2 (PS2H2) reacts with WCl6 with reduction of tungsten to give the air-sensitive tungsten(IV) complex [W{PhP(2-SC6H4)2-kappa(3)S,S',P}2] (1). 1 is oxidised in air to [WO{PhPO(2-SC6H4)2-kappa(3)S,S',O}{PhP(2-SC6H4)2-kappa(3)S,S',P}] (2). The attempted synthesis of 2 by reaction of 1 with iodosobenzene as oxidising agent was unsuccessful. [W{P(2-SC6H4)3-kappa(4)S,S',S",P}2] (3) was formed in the reaction of P(2-SHC6H4)3 (PS3H3) with WCl6. The W(VI) complex 3 contains two PS3(3-) ligands, each coordinated in a tetradentate fashion resulting in a tungsten coordination number of eight. The reaction of 3 with AgBF4 yields the dinuclear tungsten complex [W2{P(2-SC6H4)3-kappa(4)S,S',S",P}3]BF4 (4). Complexes 1-4 were characterised by spectral methods and X-ray structure determination.

  13. Suppression of the µ rhythm during speech and non-speech discrimination revealed by independent component analysis: implications for sensorimotor integration in speech processing.

    Science.gov (United States)

    Bowers, Andrew; Saltuklaroglu, Tim; Harkrider, Ashley; Cuellar, Megan

    2013-01-01

    Constructivist theories propose that articulatory hypotheses about incoming phonetic targets may function to enhance perception by limiting the possibilities for sensory analysis. To provide evidence for this proposal, it is necessary to map ongoing, high-temporal resolution changes in sensorimotor activity (i.e., the sensorimotor μ rhythm) to accurate speech and non-speech discrimination performance (i.e., correct trials.). Sixteen participants (15 female and 1 male) were asked to passively listen to or actively identify speech and tone-sweeps in a two-force choice discrimination task while the electroencephalograph (EEG) was recorded from 32 channels. The stimuli were presented at signal-to-noise ratios (SNRs) in which discrimination accuracy was high (i.e., 80-100%) and low SNRs producing discrimination performance at chance. EEG data were decomposed using independent component analysis and clustered across participants using principle component methods in EEGLAB. ICA revealed left and right sensorimotor µ components for 14/16 and 13/16 participants respectively that were identified on the basis of scalp topography, spectral peaks, and localization to the precentral and postcentral gyri. Time-frequency analysis of left and right lateralized µ component clusters revealed significant (pFDRspeech discrimination trials relative to chance trials following stimulus offset. Findings are consistent with constructivist, internal model theories proposing that early forward motor models generate predictions about likely phonemic units that are then synthesized with incoming sensory cues during active as opposed to passive processing. Future directions and possible translational value for clinical populations in which sensorimotor integration may play a functional role are discussed.

  14. Calumenin interacts with serum amyloid P component

    DEFF Research Database (Denmark)

    Vorum, H; Jacobsen, Christian; Honoré, Bent

    2000-01-01

    We recently reported the identification of human calumenin, a novel Ca(2+) binding, transformation-sensitive and secreted protein [Vorum et al. (1998) Biochim. Biophys. Acta 1386, 121-131; Vorum et al. (1999) Exp. Cell Res. 248, 473-481] belonging to the family of multiple EF-hand proteins...... with calumenin in the presence of Ca(2+). Amino acid sequencing identified this protein as serum amyloid P component (SAP). Furthermore, we verified and characterized the calumenin-SAP interaction by the surface plasmon resonance technique. The findings indicate that calumenin may participate...... in the immunological defense system and could be involved in the pathological process of amyloidosis that leads to formation of amyloid deposits seen in different types of tissues. Udgivelsesdato: 2000-Jan-14...

  15. Relativistic and Non-Relativistic Electronic Molecular-Structure Calculations for Dimers of 4p-, 5p-, and 6p-Block Elements

    DEFF Research Database (Denmark)

    Hofener, S.; Ahlrichs, R.; Knecht, S.

    2012-01-01

    We report results of non-relativistic and two-component relativistic single-reference coupled-cluster with single and double and perturbative triple excitations [CCSD(T)] treatments for the 4p-block dimers Ga2 to Br2, the 5p-block dimers In2 to I2, and their atoms. Extended basis sets up...

  16. Functional analysis of CYP6ER1, a P450 gene associated with imidacloprid resistance in Nilaparvata lugens

    OpenAIRE

    Pang, Rui; Chen, Meng; Liang, Zhikun; Yue, Xiangzhao; Ge, Hu; Zhang, Wenqing

    2016-01-01

    The cytochrome P450 CYP6ER1 has been reported to play an important role in imidacloprid resistance of the brown planthopper (BPH), Nilaparvata lugens, and is overexpressed in most resistant populations. In the present study, we confirmed that CYP6ER1 expression can be induced by certain levels of imidacloprid. Developmental expression analysis revealed that CYP6ER1 was expressed highly in the adult stage, and tissue distribution analysis showed that CYP6ER1 was expressed mainly in the fat bod...

  17. Interactions between mRNA export commitment, 3'-end quality control, and nuclear degradation

    DEFF Research Database (Denmark)

    Libri, Domenico; Dower, Ken; Boulay, Jocelyne

    2002-01-01

    Several aspects of eukaryotic mRNA processing are linked to transcription. In Saccharomyces cerevisiae, overexpression of the mRNA export factor Sub2p suppresses the growth defect of hpr1 null cells, yet the protein Hpr1p and the associated THO protein complex are implicated in transcriptional el...... results show that several classes of defective RNPs are subject to a quality control step that impedes release from transcription site foci and suggest that suboptimal messenger ribonucleoprotein assembly leads to RNA degradation by Rrp6p....

  18. Restriction of human herpesvirus 6B replication by p53

    DEFF Research Database (Denmark)

    Øster, Bodil; Kofod-Olsen, Emil; Bundgaard, Bettina

    2008-01-01

    Human herpesvirus 6B (HHV-6B) induces significant accumulation of p53 in both the nucleus and cytoplasm during infection. Activation of p53 by DNA damage is known to induce either growth arrest or apoptosis; nevertheless, HHV-6B-infected cells are arrested in their cell cycle independently of p53...

  19. The dehydrogenase region of the NADPH oxidase component Nox2 acts as a protein disulfide isomerase (PDI) resembling PDIA3 with a role in the binding of the activator protein p67phox

    Science.gov (United States)

    Bechor, Edna; Dahan, Iris; Fradin, Tanya; Berdichevsky, Yevgeny; Zahavi, Anat; Rafalowski, Meirav; Federman-Gross, Aya; Pick, Edgar

    2015-02-01

    The superoxide (O2.-)-generating NADPH oxidase of phagocytes consists of a membrane component, cytochrome b558 (a heterodimer of Nox2 and p22phox), and four cytosolic components, p47phox, p67phox, p40phox, and Rac. The catalytic component, responsible for O2.- generation, is Nox2. It is activated by the interaction of the dehydrogenase region (DHR) of Nox2 with the cytosolic components, principally with p67phox. Using a peptide-protein binding assay, we found that Nox2 peptides containing a 369CysGlyCys371 triad (CGC) bound p67phox with high affinity, dependent upon the establishment of a disulfide bond between the two cysteines. Serially truncated recombinant Nox2 DHR proteins bound p67phox only when they comprised the CGC triad. CGC resembles the catalytic motif (CGHC) of protein disulfide isomerases (PDIs). This led to the hypothesis that Nox2 establishes disulfide bonds with p67phox via a thiol-dilsulfide exchange reaction and, thus, functions as a PDI. Evidence for this was provided by the following: 1. Recombinant Nox2 protein, which contained the CGC triad, exhibited PDI-like disulfide reductase activity; 2. Truncation of Nox2 C-terminal to the CGC triad or mutating C369 and C371 to R, resulted in loss of PDI activity; 3. Comparison of the sequence of the DHR of Nox2 with PDI family members revealed three small regions of homology with PDIA3; 4. Two monoclonal anti-Nox2 antibodies, with epitopes corresponding to regions of Nox2/PDIA3 homology, reacted with PDIA3 but not with PDIA1; 5. A polyclonal anti-PDIA3 (but not an anti-PDIA1) antibody reacted with Nox2; 6. p67phox, in which all cysteines were mutated to serines, lost its ability to bind to a Nox2 peptide containing the CGC triad and had an impaired capacity to support oxidase activity in vitro. We propose a model of oxidase assembly in which binding of p67phox to Nox2 via disulfide bonds, by virtue of the intrinsic PDI activity of Nox2, stabilizes the primary interaction between the two components.

  20. Nucleus-associated phosphorylation of Ins(1,4,5)P3 to InsP6 in Dictyostelium

    NARCIS (Netherlands)

    Kaay, Jeroen van der; Wesseling, Jelle; Haastert, Peter J.M. van

    1995-01-01

    Although many cells contain large amounts of InsP(6), its metabolism and function is still largely unknown. In Dictyostelium lysates, the formation of InsP(6) by sequential phosphorylation of inositol via Ins(3,4,6)P-3 has been described [Stevens and Irvine (1990) Nature (London) 346, 580-583]; the

  1. NVL2, a nucleolar AAA-ATPase, is associated with the nuclear exosome and is involved in pre-rRNA processing

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikatsu, Yuki [Department of Life Systems, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima 770-8506 (Japan); Ishida, Yo-ichi; Sudo, Haruka [Department of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588 (Japan); Yuasa, Keizo; Tsuji, Akihiko [Department of Life Systems, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima 770-8506 (Japan); Nagahama, Masami, E-mail: nagahama@my-pharm.ac.jp [Department of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588 (Japan)

    2015-08-28

    Nuclear VCP-like 2 (NVL2) is a member of the chaperone-like AAA-ATPase family and is involved in the biosynthesis of 60S ribosomal subunits in mammalian cells. We previously showed the interaction of NVL2 with a DExD/H-box RNA helicase MTR4/DOB1, which is a known cofactor for an exoribonuclease complex, the exosome. This finding implicated NVL2 in RNA metabolic processes during ribosome biogenesis. In the present study, we found that a series of mutations within the ATPase domain of NVL2 causes a defect in pre-rRNA processing into mature 28S and 5.8S rRNAs. Co-immunoprecipitation analysis showed that NVL2 was associated with the nuclear exosome complex, which includes RRP6 as a nucleus-specific catalytic subunit. This interaction was prevented by depleting either MTR4 or RRP6, indicating their essential role in mediating this interaction with NVL2. Additionally, knockdown of MPP6, another cofactor for the nuclear exosome, also prevented the interaction by causing MTR4 to dissociate from the nuclear exosome. These results suggest that NVL2 is involved in pre-rRNA processing by associating with the nuclear exosome complex and that MPP6 is required for maintaining the integrity of this rRNA processing complex. - Highlights: • ATPase-deficient mutants of NVL2 have decreased pre-rRNA processing. • NVL2 associates with the nuclear exosome through interactions with MTR4 and RRP6. • MPP6 stabilizes MTR4-RRP6 interaction and allows NVL2 to interact with the complex.

  2. Molecular Mechanism of Enhanced Anticancer Effect of Nanoparticle Formulated LY2835219 via p16-CDK4/6-pRb Pathway in Colorectal Carcinoma Cell Line

    Directory of Open Access Journals (Sweden)

    Xu Tang

    2016-01-01

    Full Text Available LY2835219 is a dual inhibitor to CDK4 and CDK6. This study was to prepare LY2835219-loaded chitosan nanoparticles (CNP/LY and LY2835219-loaded hyaluronic acid-conjugated chitosan nanoparticles (HACNP/LY and revealed their anticancer effect and influence on p16-CDK4/6-pRb pathway against colon cell line. The nanoparticle sizes of CNP/LY and HACNP/LY were approximately 195±39.6 nm and 217±31.1 nm, respectively. The zeta potentials of CNP/LY and HACNP/LY were 37.3±1.5 mV and 30.3±2.2 mV, respectively. And the preparation process showed considerable drug encapsulation efficiency and loading efficiency. LY2835219, CNP/LY, and HACNP/LY inhibited HT29 cell proliferation with 0.68, 0.54, and 0.30 μM of IC50, respectively. G1 phase was arrested by LY2835219 and its formulations. Furthermore, inhibition of CDK4/6 by LY2835219 formulations induced CDK4, CDK6, cyclin D1, and pRb decrease and p16 increase at both protein and mRNA levels. Overall, nanoparticle formulated LY2835219 could enhance the cytotoxicity and cell cycle arrest, and HACNP/LY strengthened the trend furtherly compared to CNP/LY. It is the first time to demonstrate the anticancer effect and mechanism against HT29 by LY2835219 and its nanoparticles. The drug and its nanoparticle formulations delay the cell growth and arrest cell cycle through p16-CDK4/6-pRb pathway, while the nanoparticle formulated LY2835219 could strengthen the process.

  3. Comparison between p6P thin films and nanofibers on transistor platforms

    DEFF Research Database (Denmark)

    Tavares, Luciana; Kjelstrup-Hansen, Jakob; Thilsing-Hansen, Kasper

    2010-01-01

    The organic semiconductor para-hexaphenylene (p-6P) can be used as the light-emitting material in organic light-emitting field-effect transistors (OLEFETs), has a low cost, and is easy to process which could allow, for example, the development of mechanically flexible optoelectronics. In this work...

  4. Photoionization from the 6p 2P3/2 state of neutral cesium

    International Nuclear Information System (INIS)

    Haq, S. U.; Nadeem, Ali

    2010-01-01

    We report the photoionization studies of cesium from the 6p 2 P 3/2 excited state to measure the photoionization cross section at and above the first ionization threshold, oscillator strength of the highly excited transitions, and extension in the Rydberg series. The photoionization cross section at the first ionization threshold is measured as 25 (4) Mb and at excess energies 0.02, 0.04, 0.07, and 0.09 eV as 21, 19, 17, and 16 Mb, respectively. Oscillator strength of the 6p 2 P 3/2 → nd 2 D 5/2 (23 ≤ n ≤ 60) Rydberg transitions has been extracted utilizing the threshold value of photoionization cross section and the recorded nd 2 D 5/2 photoionization spectra.

  5. Autocrine Regulation of UVA-Induced IL-6 Production via Release of ATP and Activation of P2Y Receptors

    Science.gov (United States)

    Kawano, Ayumi; Kadomatsu, Remi; Ono, Miyu; Kojima, Shuji; Tsukimoto, Mitsutoshi; Sakamoto, Hikaru

    2015-01-01

    Extracellular nucleotides, such as ATP, are released from cells in response to various stimuli and act as intercellular signaling molecules through activation of P2 receptors. Exposure to the ultraviolet radiation A (UVA) component of sunlight causes molecular and cellular damage, and in this study, we investigated the involvement of extracellular nucleotides and P2 receptors in the UVA-induced cellular response. Human keratinocyte-derived HaCaT cells were irradiated with a single dose of UVA (2.5 J/cm2), and ATP release and interleukin (IL)-6 production were measured. ATP was released from cells in response to UVA irradiation, and the release was blocked by pretreatment with inhibitors of gap junction hemichannels or P2X7 receptor antagonist. IL-6 production was increased after UVA irradiation, and this increase was inhibited by ecto-nucleotidase or by antagonists of P2Y11 or P2Y13 receptor. These results suggest that UVA-induced IL-6 production is mediated by release of ATP through hemichannels and P2X7 receptor, followed by activation of P2Y11 and P2Y13 receptors. Interestingly, P2Y11 and P2Y13 were associated with the same pattern of IL-6 production, though they trigger different intracellular signaling cascades: Ca2+-dependent and PI3K-dependent, respectively. Thus, IL-6 production in response to UVA-induced ATP release involves at least two distinct pathways, mediated by activation of P2Y11 and P2Y13 receptors. PMID:26030257

  6. Can a Gleason 6 or Less Microfocus of Prostate Cancer in One Biopsy and Prostate-Specific Antigen Level <10 ng/mL Be Defined as the Archetype of Low-Risk Prostate Disease?

    Directory of Open Access Journals (Sweden)

    Gianluigi Taverna

    2012-01-01

    Full Text Available Prostate cancer (PC remains a cause of death worldwide. Here we investigate whether a single microfocus of PC at the biopsy (graded as Gleason 6 or less, ≤5% occupancy and the PSA <10 ng/mL can define the archetype of low-risk prostate disease. 4500 consecutive patients were enrolled. Among them, 134 patients with a single micro-focus of PC were followed up, and the parameters influencing the biochemical relapse (BR were analysed. Out of 134 patients, 94 had clinically significant disease, specifically in 74.26% of the patients with PSA <10 ng/mL. Positive surgical margins and the extracapsular invasion were found in 29.1% and 51.4% patients, respectively. BR was observed in 29.6% of the patients. Cox regression evidenced a correlation between the BR and Gleason grade at the retropubic radical prostatectomy (RRP, capsular invasion, and the presence of positive surgical margins. Multivariate regression analysis showed a statistically significant correlation between the presence of surgical margins at the RRP and BR. Considering a single micro-focus of PC at the biopsy and PSA serum level <10 ng/mL, clinically significant disease was found in 74.26% patients and only positive surgical margins are useful for predicting the BR.

  7. Comparison of mitochondrial and nucleolar RNase MRP reveals identical RNA components with distinct enzymatic activities and protein components.

    Science.gov (United States)

    Lu, Qiaosheng; Wierzbicki, Sara; Krasilnikov, Andrey S; Schmitt, Mark E

    2010-03-01

    RNase MRP is a ribonucleoprotein endoribonuclease found in three cellular locations where distinct substrates are processed: the mitochondria, the nucleolus, and the cytoplasm. Cytoplasmic RNase MRP is the nucleolar enzyme that is transiently relocalized during mitosis. Nucleolar RNase MRP (NuMRP) was purified to homogeneity, and we extensively purified the mitochondrial RNase MRP (MtMRP) to a single RNA component identical to the NuMRP RNA. Although the protein components of the NuMRP were identified by mass spectrometry successfully, none of the known NuMRP proteins were found in the MtMRP preparation. Only trace amounts of the core NuMRP protein, Pop4, were detected in MtMRP by Western blot. In vitro activity of the two enzymes was compared. MtMRP cleaved only mitochondrial ORI5 substrate, while NuMRP cleaved all three substrates. However, the NuMRP enzyme cleaved the ORI5 substrate at sites different than the MtMRP enzyme. In addition, enzymatic differences in preferred ionic strength confirm these enzymes as distinct entities. Magnesium was found to be essential to both enzymes. We tested a number of reported inhibitors including puromycin, pentamidine, lithium, and pAp. Puromycin inhibition suggested that it binds directly to the MRP RNA, reaffirming the role of the RNA component in catalysis. In conclusion, our study confirms that the NuMRP and MtMRP enzymes are distinct entities with differing activities and protein components but a common RNA subunit, suggesting that the RNA must be playing a crucial role in catalytic activity.

  8. Relativistic and Non-Relativistic Electronic Molecular-Structure Calculations for Dimers of 4p-, 5p-, and 6p-Block Elements

    NARCIS (Netherlands)

    Hoefener, S.; Ahlrichs, R.; Knecht, S.; Visscher, L.

    2012-01-01

    We report results of non-relativistic and two-component relativistic single-reference coupled-cluster with single and double and perturbative triple excitations [CCSD(T)] treatments for the 4p-block dimers Ga

  9. Quasimolecular emission near the Xe(5p 56s 1,3 P 1 - 5p 6 1 S 0) and Kr (4p 55s 1,3 P 1 - 4p 6 1 S 0) resonance lines induced by collisions with He atoms

    Science.gov (United States)

    Alekseeva, O. S.; Devdariani, A. Z.; Grigorian, G. M.; Lednev, M. G.; Zagrebin, A. L.

    2017-02-01

    This study is devoted to the theoretical investigation of the quasimolecular emission of Xe*-He and Kr*-He collision pairs near the Xe (5p 56s 1,3 P 1 - 5p 6 1 S 0) and Kr (4p 55s 1,3 P 1 - 4p 6 1 S 0) resonance atomic lines. The potential curves of the quasimolecules Xe(5p 56s) + He and Kr(4p 55s) + He have been obtained with the use of the effective Hamiltonian and pseudopotential methods. Based on these potential curves the processes of quasimolecular emission of Xe*+He and Kr*+He mixtures have been considered and the spectral distributions I(ħΔω) of photons emitted have been obtained in the framework of quasistatic approximation.

  10. Ge 3P 6Si 2O 25: A cage structure closely related to the intersecting tunnel structure KMo 3P 6Si 2O 25

    Science.gov (United States)

    Leclaire, A.; Raveau, B.

    1988-08-01

    A germanosilicophosphate Ge 3P 6Si 2O 25 has been isolated. Its structure was solved from a single-crystal study in the space group P overline31c . Its cell parameters are a = b = 7.994(1) Å, c = 16.513(2) Å, Z = 2. The refinement by full-matrix least-squares calculations leads to R = 0.043 with 686 independent reflections. The structure of this oxide is built up from corner-sharing PO 4 and SiO 4 tetrahedra and GeO 6 octahedra. One observes a feature common to several silicophosphates: the presence of the structural unit P 6Si 2O 25 built up from a disilicate group sharing its corners with six PO 4 tetrahedra. The structural relationships between this oxide and the silicophosphates AMo 3P 6Si 2O 25 and Si 3P 6Si 2O 25 (or Ge 3P 6 Ge 2O 25) are described.

  11. Atomic structure of the sweet-tasting protein thaumatin I at pH 8.0 reveals the large disulfide-rich region in domain II to be sensitive to a pH change.

    OpenAIRE

    Masuda, Tetsuya; Ohta, Keisuke; Mikami, Bunzo; Kitabatake, Naofumi; Tani, Fumito

    2012-01-01

    Thaumatin, an intensely sweet-tasting plant protein, elicits a sweet taste at 50 nM. Although the sweetness remains when thaumatin is heated at 80 °C for 4h under acid conditions, it rapidly declines when heating at a pH above 6.5. To clarify the structural difference at high pH, the atomic structure of a recombinant thaumatin I at pH 8.0 was determined at a resolution of 1.0Å. Comparison to the crystal structure of thaumatin at pH 7.3 and 7.0 revealed the root-mean square deviation value of ...

  12. Office-Based vs Traditional Operating Room Management of Recurrent Respiratory Papillomatosis: Impact of Patient Characteristics and Disease Severity.

    Science.gov (United States)

    Tatar, Emel Çadalli; Kupfer, Robbi A; Barry, Jonnae Y; Allen, Clint T; Merati, Albert L

    2017-01-01

    Management of recurrent respiratory papillomatosis (RRP) in adults has evolved to include office-based laser techniques. To determine whether demographic or disease characteristics differ between patients undergoing office-based (office group) vs traditional operating room (OR group) surgical approaches for RRP. This study was a medical record review of adult patients with RRP treated between January 2011 and September 2013 at a tertiary care center. Patients were divided into 2 groups according to the setting in which the patient had the most procedures during the past 2 years. Demographic and disease characteristics were compared between patients receiving predominantly office-based vs predominantly OR management. Of 57 patients (47 male and 10 female, with a mean [SD] age of 53.5 [16.4] years) treated during the 2-year period, 34 patients underwent predominantly office-based management and 23 patients underwent predominantly OR management. Sex, age, and weight were not statistically significantly different between the 2 groups. Patients in the OR group had a younger age at RRP diagnosis (mean [SD], 28.7 [22.0] years in the OR group and 45.5 [20.5] years in the office group), with a mean difference of 16.8 years (95% CI, -28.3 to -5.4 years). Patients in the OR group also had a significantly higher Derkay score (mean [SD], 15.1 [5.7] in the OR group and 10.7 [5.0] in the office group), with a mean difference of 4.4 (95% CI, 1.6-7.3). No statistically significant differences in comorbidities were observed between the 2 groups except for type 1 or 2 diabetes, which was more common in the OR group. There were 5 patients (22%) with diabetes in the OR group and 1 patient (3%) with diabetes in the office group, with a mean difference of 19% (95% CI, 2.7%-35%). In a subanalysis that excluded patients with juvenile-onset RRP, Derkay score (mean [SD], 13.9 [4.5] in the OR group and 10.8 [5.1] in the office group), with a mean difference of 3.1 (95% CI, 0.5-6.1), and the

  13. Component characterization and predictive modeling for green roof substrates optimized to adsorb P and improve runoff quality: A review.

    Science.gov (United States)

    Jennett, Tyson S; Zheng, Youbin

    2018-06-01

    This review is a synthesis of the current knowledge regarding the effects of green roof substrate components and their retentive capacity for nutrients, particularly phosphorus (P). Substrates may behave as either sources or sinks of P depending on the components they are formulated from, and to date, the total P-adsorbing capacity of a substrate has not been quantified as the sum of the contributions of its components. Few direct links have been established among substrate components and their physicochemical characteristics that would affect P-retention. A survey of recent literature presented herein highlights the trends within individual component selection (clays and clay-like material, organics, conventional soil and sands, lightweight inorganics, and industrial wastes and synthetics) for those most common during substrate formulation internationally. Component selection will vary with respect to ease of sourcing component materials, cost of components, nutrient-retention capacity, and environmental sustainability. However, the number of distinct components considered for inclusion in green roof substrates continues to expand, as the desires of growers, material suppliers, researchers and industry stakeholders are incorporated into decision-making. Furthermore, current attempts to characterize the most often used substrate components are also presented whereby runoff quality is correlated to entire substrate performance. With the use of well-described characterization (constant capacitance model) and modeling techniques (the soil assemblage model), it is proposed that substrates optimized for P adsorption may be developed through careful selection of components with prior knowledge of their chemical properties, that may increase retention of P in plant-available forms, thereby reducing green roof fertilizer requirements and P losses in roof runoff. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Family-based Association Analyses of Imputed Genotypes Reveal Genome-Wide Significant Association of Alzheimer’s disease with OSBPL6, PTPRG and PDCL3

    Science.gov (United States)

    Herold, Christine; Hooli, Basavaraj V.; Mullin, Kristina; Liu, Tian; Roehr, Johannes T; Mattheisen, Manuel; Parrado, Antonio R.; Bertram, Lars; Lange, Christoph; Tanzi, Rudolph E.

    2015-01-01

    The genetic basis of Alzheimer's disease (AD) is complex and heterogeneous. Over 200 highly penetrant pathogenic variants in the genes APP, PSEN1 and PSEN2 cause a subset of early-onset familial Alzheimer's disease (EOFAD). On the other hand, susceptibility to late-onset forms of AD (LOAD) is indisputably associated to the ε4 allele in the gene APOE, and more recently to variants in more than two-dozen additional genes identified in the large-scale genome-wide association studies (GWAS) and meta-analyses reports. Taken together however, although the heritability in AD is estimated to be as high as 80%, a large proportion of the underlying genetic factors still remain to be elucidated. In this study we performed a systematic family-based genome-wide association and meta-analysis on close to 15 million imputed variants from three large collections of AD families (~3,500 subjects from 1,070 families). Using a multivariate phenotype combining affection status and onset age, meta-analysis of the association results revealed three single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with AD risk: rs7609954 in the gene PTPRG (P-value = 3.98·10−08), rs1347297 in the gene OSBPL6 (P-value = 4.53·10−08), and rs1513625 near PDCL3 (P-value = 4.28·10−08). In addition, rs72953347 in OSBPL6 (P-value = 6.36·10−07) and two SNPs in the gene CDKAL1 showed marginally significant association with LOAD (rs10456232, P-value: 4.76·10−07; rs62400067, P-value: 3.54·10−07). In summary, family-based GWAS meta-analysis of imputed SNPs revealed novel genomic variants in (or near) PTPRG, OSBPL6, and PDCL3 that influence risk for AD with genome-wide significance. PMID:26830138

  15. Degradation Signals Recognized by the Ubc6p-Ubc7p Ubiquitin-Conjugating Enzyme Pair

    Science.gov (United States)

    Gilon, Tamar; Chomsky, Orna; Kulka, Richard G.

    2000-01-01

    Proteolysis by the ubiquitin-proteasome system is highly selective. Specificity is achieved by the cooperation of diverse ubiquitin-conjugating enzymes (Ubcs or E2s) with a variety of ubiquitin ligases (E3s) and other ancillary factors. These recognize degradation signals characteristic of their target proteins. In a previous investigation, we identified signals directing the degradation of β-galactosidase and Ura3p fusion proteins via a subsidiary pathway of the ubiquitin-proteasome system involving Ubc6p and Ubc7p. This pathway has recently been shown to be essential for the degradation of misfolded and regulated proteins in the endoplasmic reticulum (ER) lumen and membrane, which are transported to the cytoplasm via the Sec61p translocon. Mutant backgrounds which prevent retrograde transport of ER proteins (hrd1/der3Δ and sec61-2) did not inhibit the degradation of the β-galactosidase and Ura3p fusions carrying Ubc6p/Ubc7p pathway signals. We therefore conclude that the ubiquitination of these fusion proteins takes place on the cytosolic face of the ER without prior transfer to the ER lumen. The contributions of different sequence elements to a 16-amino-acid-residue Ubc6p-Ubc7p-specific signal were analyzed by mutation. A patch of bulky hydrophobic residues was an essential element. In addition, positively charged residues were found to be essential. Unexpectedly, certain substitutions of bulky hydrophobic or positively charged residues with alanine created novel degradation signals, channeling the degradation of fusion proteins to an unidentified proteasomal pathway not involving Ubc6p and Ubc7p. PMID:10982838

  16. Posterior and anterior fixation of the urethra during robotic prostatectomy improves early continence rates.

    Science.gov (United States)

    Koliakos, Nikolaos; Mottrie, Alexandre; Buffi, Nicolo; De Naeyer, Geert; Willemsen, Pieter; Fonteyne, Etienne

    2010-02-01

    To investigate whether posterior and anterior fixation of the vesicourethral anastomosis during robotic radical prostatectomy (RRP) helps to establish continence earlier. Forty-seven consecutive patients undergoing RRP were randomized into two groups. The first group received a typical Van Velthoven vesicourethral anastomosis and the second group a modified anastomosis with posterior and anterior fixation. In this group the posterior fibrous tissues of the sphincter were sutured to the residual Denonvilliers' fascia. The anastomosis with two running sutures started at the 6 o'clock position on the bladder neck and continued upwards. Two-step stitching was done on the upper half of the anastomosis to ensure good stabilization of the bladder: a small portion of urethral stump followed by a deep haemostatic stitch on the plexus. Continence, as measured by patient self-reporting of the number of pads used per 24 h, was assessed 7 weeks after catheter removal, by telephone interview. The use of no pads or one pad was defined as "continent", two pads as "moderate incontinence" and more than two pads as "severe incontinence". At catheter removal, more patients in the fixation group were continent than in the Van Velthoven group [9/23 (39%) vs 3/24 (12.5%), p = 0.036]. At 7 weeks, continence was even better in the fixation group [15/23 (65%) vs 8/24 (33%), p = 0. 029]. The mean pad usage was less in the fixation group (1.43 vs 2.25, p = 0.032). The posterior and anterior fixation of the vesicourethral anastomosis during RRP results in an intact sphincteric mechanism, because no stretch is applied to the urethra, resulting in earlier continence.

  17. Anatomic Considerations for Radical Retropubic Prostatectomy in an Achondroplastic Dwarf

    Directory of Open Access Journals (Sweden)

    Dennis Gyomber

    2009-01-01

    Full Text Available This is the first report of a radical retropubic prostatectomy (RRP in an achondroplastic dwarf. We highlight the pelvic anatomy, precluding laparoscopic or robotic prostatectomy, and making open surgery extremely difficult. We review relevant literature regarding general, urological, and orthopedic abnormalities of achondroplasia (ACH and present a clinical case. No reports of RRP in achondroplastic dwarfs exist, with only one case of an abandoned RRP due to similar pelvic anatomy in a patient with osteogenesis imperfecta. Significant lumbar lordosis found in ACH results in a short anteroposterior dimension, severely limiting access to the prostate. We present a case of a 62-year-old achondroplastic dwarf who had Gleason 3+4 disease on transrectal ultrasound-guided biopsy in four from 12 cores. Surgery was difficult due to narrow anteroposterior pelvic dimension, but achievable. Histological analysis revealed multifocal prostate cancer, with negative surgical margins and no extraprostatic extension. RRP in ACH patients, although possible, should be approached with caution due to the abnormal pelvic dimensions, and discussions regarding potential abandonment of surgery should be included during informed consent. This case highlights the preoperative use of computed tomography to assist in the surgical planning for patients with difficult pelvic anatomy.

  18. An analysis of few-body cross sections in pp and πp interactions in terms of the two-component picture

    International Nuclear Information System (INIS)

    Karimaeki, V.

    1975-01-01

    The energy behaviour of total cross sections of exclusive channel with one, two or three produced pions has been studied in pp and πp interactions. Two components, interpreted as diffractive and non-diffractive, have been fitted to the cross section data assuming an asymptotic power law dependence in psub(lab) for both. Isotopic spin factors were used as constraints to fit different charge channels simultaneously as well as for determining diffractive cross sections for non-observable few-body channels. The diffractive component for fixed multiplicity is found to decrease as psub(lab)sup(-0.16+-0.04). Results are compared with the predictions of factorization and semilocal factorization hypotheses. Total diffractive cross sections derived by the analysis are 5.1+-0.6 mb in pp and 2.2+-0.3 mb in πp interactions at psub(lab)=10 GeV/c. (author)

  19. Revealing the Structural Complexity of Component Interactions of Topic-Specific PCK when Planning to Teach

    Science.gov (United States)

    Mavhunga, Elizabeth

    2018-04-01

    Teaching pedagogical content knowledge (PCK) at a topic-specific level requires clarity on the content-specific nature of the components employed, as well as the specific features that bring about the desirable depth in teacher explanations. Such understanding is often hazy; yet, it influences the nature of teacher tasks and learning opportunities afforded to pre-service teachers in a teaching program. The purpose of this study was twofold: firstly, to illuminate the emerging complexity when content-specific components of PCK interact when planning to teach a chemistry topic; and secondly, to identify the kinds of teacher tasks that promote the emergence of such complexity. Data collected were content representations (CoRes) in chemical equilibrium accompanied by expanded lesson outlines from 15 pre-service teachers in their final year of study towards a first degree in teaching (B Ed). The analysis involved extraction of episodes that exhibited component interaction by using a qualitative in-depth analysis method. The results revealed the structure in which the components of PCK in a topic interact among each other to be linear, interwoven, or a combination of the two. The interwoven interactions contained multiple components that connected explanations on different aspects of a concept, all working in a complementary manner. The most sophisticated component interactions emerged from teacher tasks on descriptions of a lesson sequence and a summary of a lesson. Recommendations in this study highlight core practices for making pedagogical transformation of topic content knowledge more accessible.

  20. Fluorescence lifetime components reveal kinetic intermediate states upon equilibrium denaturation of carbonic anhydrase II.

    Science.gov (United States)

    Nemtseva, Elena V; Lashchuk, Olesya O; Gerasimova, Marina A; Melnik, Tatiana N; Nagibina, Galina S; Melnik, Bogdan S

    2017-12-21

    In most cases, intermediate states of multistage folding proteins are not 'visible' under equilibrium conditions but are revealed in kinetic experiments. Time-resolved fluorescence spectroscopy was used in equilibrium denaturation studies. The technique allows for detecting changes in the conformation and environment of tryptophan residues in different structural elements of carbonic anhydrase II which in its turn has made it possible to study the intermediate states of carbonic anhydrase II under equilibrium conditions. The results of equilibrium and kinetic experiments using wild-type bovine carbonic anhydrase II and its mutant form with the substitution of leucine for alanine at position 139 (L139A) were compared. The obtained lifetime components of intrinsic tryptophan fluorescence allowed for revealing that, the same as in kinetic experiments, under equilibrium conditions the unfolding of carbonic anhydrase II ensues through formation of intermediate states.

  1. Spin dynamics of light-induced charge separation in composites of semiconducting polymers and PC60BM revealed using Q-band pulse EPR.

    Science.gov (United States)

    Lukina, E A; Suturina, E; Reijerse, E; Lubitz, W; Kulik, L V

    2017-08-23

    Light-induced processes in composites of semiconducting polymers and fullerene derivatives have been widely studied due to their usage as active layers of organic solar cells. However the process of charge separation under light illumination - the key process of an organic solar cell is not well understood yet. Here we report a Q-band pulse electron paramagnetic resonance study of composites of the fullerene derivative PC 60 BM ([6,6]-phenyl-C 61 -butyric acid methyl ester) with different p-type semiconducting polymers regioregular and regiorandom P3HT (poly(3-hexylthiophene-2,5-diyl), MEH-PPV (poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene]), PCDTBT (poly[N-9'-heptadecanyl-2,7-carbazole-alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)]), PTB7 (poly({4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl}{3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl}))), resulting in a detailed description of the in-phase laser flash-induced electron spin echo (ESE) signal. We found that in organic donor-acceptor composites the laser flash simultaneously induces species of two types: a polymer˙ + /fullerene˙ - spin-correlated polaron pair (SCPP) with an initial singlet spin state and (nearly) free polymer˙ + and fullerene˙ - species with non-equilibrium spin polarization. Species of the first type (SCPP) are well-known for polymer/fullerene blends and are usually associated with a charge-separated state. Also, spin polarization of long-living free species (polarons in deep traps) is affected by the laser flash, which is the third contribution to the flash-induced ESE signal. A protocol for extracting the in-phase ESE signal of the SCPP based on the dependence of the microwave nutation frequency on the strength of the spin coupling within the polaron pair was developed. Nutation experiments revealed an unusual pattern of the SCPP in RR-P3HT/PC 60 BM composites, from which the strength of the exchange interaction between the polymer

  2. The Nucleus of Active Asteroid 311P/(2013 P5) PANSTARRS

    Science.gov (United States)

    Jewitt, David; Weaver, Harold; Mutchler, Max; Li, Jing; Agarwal, Jessica; Larson, Stephen

    2018-06-01

    The unique inner-belt asteroid 311P/PANSTARRS (formerly P/2013 P5) is notable for its sporadic, comet-like ejection of dust in nine distinct epochs spread over ∼250 days in 2013. This curious behavior has been interpreted as the product of localized, equatorward landsliding from the surface of an asteroid rotating at the brink of instability. We obtained new Hubble Space Telescope observations to directly measure the nucleus and to search for evidence of its rapid rotation. We find a nucleus with mid-light absolute magnitude H V = 19.14 ± 0.02, corresponding to an equal-area circle with radius 190 ± 30 m (assuming geometric albedo p V = 0.29). However, instead of providing photometric evidence for rapid nucleus rotation, our data set a lower limit to the light-curve period, P ≥ 5.4 hr. The dominant feature of the light curve is a V-shaped minimum, ∼0.3 mag deep, which is suggestive of an eclipsing binary. Under this interpretation, the time-series data are consistent with a secondary/primary mass ratio, m s /m p ∼ 1:6, a ratio of separation/primary radius, r/r p ∼ 4 and an orbit period ∼0.8 days. These properties lie within the range of other asteroid binaries that are thought to be formed by rotational breakup. While the light-curve period is long, centripetal dust ejection is still possible if one or both components rotate rapidly (≲2 hr) and have small light-curve variation because of azimuthal symmetry. Indeed, radar observations of asteroids in critical rotation reveal “muffin-shaped” morphologies, which are closely azimuthally symmetric and which show minimal light curves. Our data are consistent with 311P being a close binary in which one or both components rotates near the centripetal limit. The mass loss in 2013 suggests that breakup occurred recently and could even be on-going. A search for fragments that might have been recently ejected beyond the Hill sphere reveals none larger than effective radius r e ∼ 10 m.

  3. Study on fast luminescence component induced by gamma-rays in Ce doped LiCaAlF6 scintillators

    International Nuclear Information System (INIS)

    Watanabe, Kenichi; Kondo, Yoshiyuki; Yamazaki, Atsushi; Uritani, Akira; Iguchi, Tetsuo; Kawaguchi, Noriaki; Fukuda, Kentaro; Ishizu, Sumito; Yanagida, Takayuki; Fujimoto, Yutaka; Yoshikawa, Akira

    2014-01-01

    We discuss the origin of the fast luminescence component induced by fast electrons generated in gamma-ray interactions in Ce doped LiCaAlF 6 scintillators. Although the slow luminescence component induced by Ce 3+ emissions depends on the Ce concentration in the LiCaAlF 6 scintillator, the fast component is independent. The fast component is suggested to be generated in the host matrix of the LiCaAlF 6 crystal. From quantitative considerations based on Frank–Tamm equation, which shows the light yield of the Cherenkov radiation, the Cherenkov radiation was determined as the origin of the fast component. We, additionally, found that the slow rise time of main Ce 3+ emissions in the Ce:LiCaAlF 6 scintillator plays an important role to perform the pulse shape discrimination. - Highlights: • The fast luminescence in Ce:LiCaAlF 6 scintillator is generated in the host matrix. • The origin of the fast luminescence is determined as the Cherenkov radiation. • The slow rise time also plays an important role to perform PSD

  4. Spatial distribution of intra-molecular water and polymeric components in polyelectrolyte dendrimers revealed by small angle scattering investigations

    Science.gov (United States)

    Wu, Bin; Li, Xin; Do, Changwoo; Kim, Tae-Hwan; Shew, Chwen-Yang; Liu, Yun; Yang, Jun; Hong, Kunlun; Porcar, Lionel; Chen, Chun-Yu; Liu, Emily L.; Smith, Gregory S.; Herwig, Kenneth W.; Chen, Wei-Ren

    2011-10-01

    An experimental scheme using contrast variation small angle neutron scattering technique is developed to investigate the structural characteristics of amine-terminated poly(amidoamine) dendrimers solutions. Using this methodology, we present the dependence of both the intra-dendrimer water and the polymer distribution on molecular protonation, which can be precisely adjusted by tuning the pH of the solution. Assuming spherical symmetry of the spatial arrangement of the constituent components of dendrimer, and that the atomic ratio of hydrogen-to-deuterium for the solvent residing within the cavities of dendrimer is identical to that for the solvent outside the dendrimer, the intra-dendrimer water distribution along the radial direction is determined. Our result clearly reveals an outward relocation of the peripheral groups, as well as enhanced intra-dendrimer hydration, upon increasing the molecular protonation and, therefore, allows the determination of segmental backfolding in a quantitative manner. The connection between these charge-induced structural changes and our recently observed progressively active segmental dynamics is also discussed.

  5. The use of mitomycin-C for respiratory papillomas: Clinical, histologic and biochemical correlation

    International Nuclear Information System (INIS)

    Hamza, Ashraf H.; Nasr, Manal M.; Deghady, Akram A.

    2005-01-01

    To assess the clinical effects of mitomycin-C (MMC) on human papilloma virus (HPV)-infected tissues of the airway. We included 10 patients with previous histologic diagnosis of recurrent respiratory papillomas (RRP) in this prospective study, conducted at the Department of Otolaryngology-Head and Neck Surgery, University of Alexandria, Egypt, between January 2000 and December 2002. Under general anesthesia, each patient underwent laser excision of all visible papillomas, followed by topical application of 1 cc of 0.5 mg/ml MMC. The procedure was repeated weekly until no visible papillomas could be microscopically detected. We histopathologically studied the obtained specimens and tested for the presence of HPV DNA using polymerase chain reaction (PCR) technique. We collected blood samples from all patients and from another 10 healthy volunteers for determination of serum interleukin-2 (IL-2) level using enzyme-linked immunosorbent assay technique. We achieved clinical remission in 8 of the patients (80%), a fact that was confirmed histopathologically and by PCR data. The mean serum IL-2 levels +/- SD was significantly lower in papilloma patients (83.6 +/- 28.83 pg/ml) than in control subjects (196.3 +/- 42.46 pg/ml) (p<0.01). Among patients with RRP, serum IL-2 levels +/-SD was lower in initial samples (83.6 +/- 28.83) than follow-up (95.7 +/- 27.98 and 112.3 +/- 33.8 and 129.4 +/- 34.04) and remission samples (154 +/- 37.84 pg/ml). Our result suggests that topical application of MMC may act adjunctively to laser surgery for RRP. (author)

  6. Resolution and Probabilistic Models of Components in CryoEM Maps of Mature P22 Bacteriophage

    Science.gov (United States)

    Pintilie, Grigore; Chen, Dong-Hua; Haase-Pettingell, Cameron A.; King, Jonathan A.; Chiu, Wah

    2016-01-01

    CryoEM continues to produce density maps of larger and more complex assemblies with multiple protein components of mixed symmetries. Resolution is not always uniform throughout a cryoEM map, and it can be useful to estimate the resolution in specific molecular components of a large assembly. In this study, we present procedures to 1) estimate the resolution in subcomponents by gold-standard Fourier shell correlation (FSC); 2) validate modeling procedures, particularly at medium resolutions, which can include loop modeling and flexible fitting; and 3) build probabilistic models that combine high-accuracy priors (such as crystallographic structures) with medium-resolution cryoEM densities. As an example, we apply these methods to new cryoEM maps of the mature bacteriophage P22, reconstructed without imposing icosahedral symmetry. Resolution estimates based on gold-standard FSC show the highest resolution in the coat region (7.6 Å), whereas other components are at slightly lower resolutions: portal (9.2 Å), hub (8.5 Å), tailspike (10.9 Å), and needle (10.5 Å). These differences are indicative of inherent structural heterogeneity and/or reconstruction accuracy in different subcomponents of the map. Probabilistic models for these subcomponents provide new insights, to our knowledge, and structural information when taking into account uncertainty given the limitations of the observed density. PMID:26743049

  7. In situ measurements reveal extremely low pH in soil

    DEFF Research Database (Denmark)

    Nielsen, Knud Erik; Loibide, Amaia Irixar; Nielsen, Lars Peter

    2017-01-01

    We measured pH in situ in the top organic soil horizons in heathland and pine forest and found values between 2.6 and 3.2. This was 0.5e0.8 units lower than concurrent laboratory pH measurements of the same soil, which raises questions about the interpretation of pH measurements. We propose that ...... that the higher pH recorded by standard laboratory methods may be due to buffering ions from soil biota released from drying, grinding and rewetting of soil samples, whereas the in situ pH reflects the correct level of acidification....

  8. (p,. pi. /sup -/) reaction and. delta. /sup + +/ components of nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Kisslinger, L S; Miller, G A [Carnegie-Mellon Univ., Pittsburgh, Pa. (USA). Dept. of Physics

    1975-12-08

    The use of the (p,..pi../sup -/) reaction as a probe to determine ..delta../sup + +/(1232) components of nuclear wave functions is examined within the framework of a model which treats baryon resonances on the same footing as nucleons. Nuclear structure properties which affect the ..delta..-probability are discussed. Estimates of cross sections, at several energies, are made for the ..delta../sup + +/ transfer contribution as well as for the competing processes: proton charge exchange (p,n) followed by an (n,..gamma../sup -/) reaction; emission of a ..pi../sup 0/ followed by pion charge exchange (..pi../sup -/,..pi../sup 0/). Even with ..delta..-probabilities as small as 0.0001 the ..delta..-transfer process can compete with ordinary background charge-exchange reactions.

  9. KINEMATICS OF A MECHANISM WITH STOPPINGS, BASED ON A HYPOCYCLOID WITH 6 BRANCHES

    Directory of Open Access Journals (Sweden)

    Liliana LUCA

    2010-10-01

    Full Text Available They are studied the positions, velocities and accelerations of a mechanism based on planetary gear and a RRP dyad. The mechanism ensures the plunger stop on a certain subinterval of the cycle, although the leading element is rotating. Because of the approximation of the hypocycloid shortened arc with six branches, by a circle arc, errors occur.

  10. Mathematical Modeling of E6-p53 interactions in Cervical Cancer

    Science.gov (United States)

    Khattak, Faryal; Haseeb, Muhammad; Fazal, Sahar; Bhatti, A I; Ullah, Mukhtar

    2017-04-01

    Background: Cervical cancer is the third most common cancer in women throughout the world. The human papillomavirus (HPV) E6 viral protein plays an essential role in proteasomal degradation of the cancer suppressant protein p53. As a result, p53 negative regulation and apoptosis relevant activities are abrogated, facilitating development of cervical cancer. Methods: A mathematical model of E6-p53 interactions was developed using mathematical laws. In-silico simulations were carried out on CellDesigner and as a test case the small molecule drug RITA was considered for its ability to rescue the functions of tumor suppressor p53 by inhibiting E6 mediated proteasomal degradation. Results: Using a computational model we scrutinized how p53 responds to RITA, and chemical reactions of this small molecule drug were incorporated to perceive the full effects. The evolved strategy allowed the p53 response and rescue of its tumor suppressor function to be delineated, RITA being found to block p53 interactions with E6 associated proteins. Conclusion: We could develop a model of E6-p53 interactions with incorporation of actions of the small molecule drug RITA. Suppression of E6 associated proteins by RITA induces accumulation of tumor suppressant p53. Using CellDesigner to encode the model ensured that it can be easily modified and extended as more data become available. This strategy should play an effective role in the development of therapies against cancer. Creative Commons Attribution License

  11. Component on-shell actions of supersymmetric 3-branes: I. 3-brane in D = 6

    International Nuclear Information System (INIS)

    Bellucci, S; Sutulin, A; Kozyrev, N; Krivonos, S

    2015-01-01

    In the present and accompanying papers we explicitly construct the on-shell supersymmetric component actions for 3-branes moving in D = 6 and D = 8 within the nonlinear realizations framework. In the first paper we apply our scheme to construct the action of supersymmetric 3-brane in D = 6. It turns out that all ingredients entering the component action can be obtained almost algorithmically by using the nonlinear realizations approach. Within this approach, properly adapted to the construction of the on-shell component actions, we pay much attention to broken supersymmetry. Doing so, we were able to write the action in terms of purely geometric objects (vielbeins and covariant derivatives of the physical bosonic components), covariant with respect to broken supersymmetry. It turns out that all terms of the higher orders in the fermions are hidden inside these covariant derivatives and vielbeins. Moreover, the main part of the component action just mimics its bosonic cousin in which the ordinary space–time derivatives and the bosonic worldvolume are replaced by their covariant supersymmetric analogs. The Wess–Zumino term in the action, which does not exist in the bosonic case, can be also easily constructed in terms of reduced Cartan forms. Keeping the broken supersymmetry almost explicit, one may write the ansatz for the component action, fully defined up to two constant parameters. The role of the unbroken supersymmetry is just to fix these parameters. (paper)

  12. Dissecting mechanisms of nuclear mRNA surveillance in THO/sub2 complex mutants

    DEFF Research Database (Denmark)

    Rougemaille, Mathieu; Gudipati, Rajani K; Olesen, Jens Raabjerg

    2007-01-01

    The nuclear exosome is involved in numerous RNA metabolic processes. Exosome degradation of rRNA, snoRNA, snRNA and tRNA in Saccharomyces cerevisiae is activated by TRAMP complexes, containing either the Trf4p or Trf5p poly(A) polymerase. These enzymes are presumed to facilitate exosome access...... is required for both retention and degradation of nuclear restricted mRNAs. We show here that Trf4p, in the context of TRAMP, is an mRNA surveillance factor. However, unlike Rrp6p, Trf4p only partakes in RNA degradation and not in transcript retention. Surprisingly, a polyadenylation-defective Trf4p protein...

  13. Identification of 6H1 as a P2Y purinoceptor: P2Y5.

    Science.gov (United States)

    Webb, T E; Kaplan, M G; Barnard, E A

    1996-02-06

    We have determined the identity of the orphan G-protein coupled receptor cDNA, 6H1, present in activated chicken T cells, as a subtype of P2Y purinoceptor. This identification is based on first on the degree of sequence identity shared with recently cloned members of the P2Y receptor family and second on the pharmacological profile. Upon transient expression in COS-7 cells the 6H1 receptor bound the radiolabel [35S]dATP alpha S specifically and with high affinity (Kd, 10 nM). This specific binding could be competitively displaced by a range of ligands active at P2 purinoceptors, with ATP being the most active (K (i)), 116 nM). Such competition studies have established the following rank order of activity: ATP ADP 2-methylthioATP alpha, beta-methylene ATP, UTP, thus confirming 6H1 as a member of the growing family of P2Y purinoceptors. As the fifth receptor of this type to be identified we suggest that it be named P2Y5.

  14. Error-prone bypass of O6-methylguanine by DNA polymerase of Pseudomonas aeruginosa phage PaP1.

    Science.gov (United States)

    Gu, Shiling; Xiong, Jingyuan; Shi, Ying; You, Jia; Zou, Zhenyu; Liu, Xiaoying; Zhang, Huidong

    2017-09-01

    O 6 -Methylguanine (O 6 -MeG) is highly mutagenic and is commonly found in DNA exposed to methylating agents, generally leads to G:C to A:T mutagenesis. To study DNA replication encountering O 6 -MeG by the DNA polymerase (gp90) of P. aeruginosa phage PaP1, we analyzed steady-state and pre-steady-state kinetics of nucleotide incorporation opposite O 6 -MeG by gp90 exo - . O 6 -MeG partially inhibited full-length extension by gp90 exo - . O 6 -MeG greatly reduces dNTP incorporation efficiency, resulting in 67-fold preferential error-prone incorporation of dTTP than dCTP. Gp90 exo - extends beyond T:O 6 -MeG 2-fold more efficiently than C:O 6 -MeG. Incorporation of dCTP opposite G and incorporation of dCTP or dTTP opposite O 6 -MeG show fast burst phases. The pre-steady-state incorporation efficiency (k pol /K d,dNTP ) is decreased in the order of dCTP:G>dTTP:O 6 -MeG>dCTP:O 6 -MeG. The presence of O 6 -MeG at template does not affect the binding affinity of polymerase to DNA but it weakened their binding in the presence of dCTP and Mg 2+ . Misincorporation of dTTP opposite O 6 -MeG further weakens the binding affinity of polymerase to DNA. The priority of dTTP incorporation opposite O 6 -MeG is originated from the fact that dTTP can induce a faster conformational change step and a faster chemical step than dCTP. This study reveals that gp90 bypasses O 6 -MeG in an error-prone manner and provides further understanding in DNA replication encountering mutagenic alkylation DNA damage for P. aeruginosa phage PaP1. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Solution structure of the Equine Infectious Anemia Virus p9 protein: a rationalization of its different ALIX binding requirements compared to the analogous HIV-p6 protein

    Directory of Open Access Journals (Sweden)

    Henklein Peter

    2009-12-01

    Full Text Available Abstract Background The equine infection anemia virus (EIAV p9 Gag protein contains the late (L- domain required for efficient virus release of nascent virions from the cell membrane of infected cell. Results In the present study the p9 protein and N- and C-terminal fragments (residues 1-21 and 22-51, respectively were chemically synthesized and used for structural analyses. Circular dichroism and 1H-NMR spectroscopy provide the first molecular insight into the secondary structure and folding of this 51-amino acid protein under different solution conditions. Qualitative 1H-chemical shift and NOE data indicate that in a pure aqueous environment p9 favors an unstructured state. In its most structured state under hydrophobic conditions, p9 adopts a stable helical structure within the C-terminus. Quantitative NOE data further revealed that this α-helix extends from Ser-27 to Ser-48, while the N-terminal residues remain unstructured. The structural elements identified for p9 differ substantially from that of the functional homologous HIV-1 p6 protein. Conclusions These structural differences are discussed in the context of the different types of L-domains regulating distinct cellular pathways in virus budding. EIAV p9 mediates virus release by recruiting the ALG2-interacting protein X (ALIX via the YPDL-motif to the site of virus budding, the counterpart of the YPXnL-motif found in p6. However, p6 contains an additional PTAP L-domain that promotes HIV-1 release by binding to the tumor susceptibility gene 101 (Tsg101. The notion that structures found in p9 differ form that of p6 further support the idea that different mechanisms regulate binding of ALIX to primary versus secondary L-domains types.

  16. Generation and characterization of polyclonal antibodies specific to N-terminal extension of p85 isoform of ribosomal protein S6 kinase 1 (p85 S6K1

    Directory of Open Access Journals (Sweden)

    Savinska L. O.

    2015-08-01

    Full Text Available Aim. Generation of polyclonal antibodies specific to the ribosomal protein S6 kinase isoform – p85S6K1 and directed to the N-terminal (1–23 aa extension of p85S6K1. Methods. Animal immunization with synthetic (1–23 aa peptide, ELISA, Western blot, Immunoprecipitation, immunofluorescent analysis. Results. Polyclonal antibodies have been generated, which specifically recognize only p85 but not p70 isoform of S6K1 in western blot, immunoprecipitation and immunofluorescence analysis. Conclusions. The obtained antibodies can be recommended for studies on the p85S6K1 and other S6K1 isoforms possessing the N-terminal extension – the identification of binding protein partners, analysis of subcellular localization under different physiological conditions, elucidation of the signal transduction pathways involving different S6K1 isoforms.

  17. Crystallization and preliminary X-ray analysis of the reductase component of p-hydroxyphenylacetate 3-hydroxylase from Acinetobacter baumannii

    International Nuclear Information System (INIS)

    Oonanant, Worrapoj; Sucharitakul, Jeerus; Chaiyen, Pimchai; Yuvaniyama, Jirundon

    2012-01-01

    The reductase component of p-hydroxyphenylacetate 3-hydroxylase from A. baumannii was overexpressed, purified and crystallized. X-ray diffraction data were collected and processed to 2.3 Å resolution. p-Hydroxyphenylacetate 3-hydroxylase (HPAH) from Acinetobacter baumannii catalyzes the hydroxylation of p-hydroxyphenylacetate (HPA) at the ortho position to yield 3,4-dihydroxyphenylacetate (DHPA). HPAH from A. baumannii is a two-component flavoprotein consisting of a smaller reductase (C 1 ) component and a larger oxygenase (C 2 ) component. The C 1 component supplies a reduced flavin in its free form to the C 2 counterpart for hydroxylation. In addition, HPA can bind to C 1 and enhance the flavin-reduction rate without becoming hydroxylated. The recombinant C 1 component was purified and crystallized using the microbatch method at 295 K. X-ray diffraction data were collected to 2.3 Å resolution using synchrotron radiation on the BL13B1 beamline at NSRRC, Taiwan. The crystal belonged to the orthorhombic space group P2 1 2 1 2 1 , with unit-cell parameters a = 47.78, b = 59.92, c = 211.85 Å, and contained two molecules of C 1 per asymmetric unit

  18. Protective Effects of Sonic Hedgehog Against Ischemia/Reperfusion Injury in Mouse Skeletal Muscle via AKT/mTOR/p70S6K Signaling

    Directory of Open Access Journals (Sweden)

    Qiu Zeng

    2017-10-01

    Full Text Available Background/Aims: Skeletal muscle ischemia/reperfusion (I/R injury is a common and severe disease. Sonic hedgehog (Shh plays a critical role in post-natal skeletal muscle regeneration. In the present study, the role of Shh in skeletal muscle I/R injury and the mechanisms involved were investigated. Methods: The expression of Shh, AKT/mTOR/p70S6K and apoptosis pathway components were evaluated following tourniquet-induced skeletal muscle I/R injury. Then, mice were subjected to systemic administration of cyclopamine or one-shot treatment of a plasmid encoding the human Shh gene (phShh to examine the effects of Shh on I/R injury. Moreover, mice were subjected to systemic administration of NVP-BEZ235 to investigate the role of the AKT/mTOR/p70S6K pathway in Shh-triggered skeletal muscle protection. Results: We found that the levels of Shh, AKT/mTOR/p70S6K pathway components and Cleaved Caspase 3 and the Bax/Bcl2 ratio initially increased and then decreased at different time points post-I/R injury. Moreover, Shh protected skeletal muscle against I/R injury by alleviating muscle destruction, reducing interstitial fibrosis and inhibiting apoptosis, and these protective effects were abrogated when the AKT/mTOR/p70S6K pathway was inhibited. Conclusion: Collectively, these data suggest that Shh signaling exerts a protective role through the AKT/mTOR/p70S6K signaling pathway during skeletal muscle I/R injury. Thus, Shh signaling may be a therapeutic target for protecting skeletal muscle from I/R injury.

  19. LncRNA SNHG6 is Associated with Poor Prognosis of Gastric Cancer and Promotes Cell Proliferation and EMT through Epigenetically Silencing p27 and Sponging miR-101-3p

    Directory of Open Access Journals (Sweden)

    Kai Yan

    2017-06-01

    Full Text Available Background/Amis: Long non-coding RNAs (lncRNAs, a novel class of transcripts, have been shown to play critical roles in diverse cellular biological processes, including tumorigenesis. Small nucleolar RNA host gene 6 (SNHG6 regulates various biological processes in cancer cells. However, the biological role of SNHG6 in gastric cancer still remains to be explored. The aim of this study is to investigate the characteristic of the SNHG6 in gastric cancer. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR was used to measure the expression of SNHG6 in gastric cancer tissues and cell lines. MTT assays, colony formation assays were used to determine the impact of SNHG6 on tumorigenesis . Flow cytometric analysis of cell cycle and apoptosis was performed to measure the effect of SNHG6 on cell cycle and apoptosis rate. Transwell assay was performed to measure the effect of SNHG6 on cell migration. Western blotting and immunofuorescence were utilized to examine the effect of SNHG6 on epithelial-mesenchymal transition (EMT of GC cells. Chromatin immunoprecipitation (ChIP, RNA immunoprecipitation (RIP, RNA-pulldown and luciferase reporter assays were employed to dissect molecular mechanisms. Results: In this study, we revealed that SNHG6 was overexpressed in gastric cancer tissues and cell lines. High expression levels of SNHG6 wereassociated with invasion depth, lymph node metastasis, distant metastasis and tumor/node/metastasis (TNM stage, and predicted poor prognosis. Loss-of-function assays revealed that silenced SNHG6 obviously inhibited gastric cancer cell growth, weakened cell migration capacity and suppressed the EMT processes of gastric cancer cells. Additionally, ChIP, RIP, RNA-pulldown and luciferase reporter assays evidenced that SNHG6 could epigenetically silenced p27 and could competitively sponging miR-101-3p thereby regulating zinc finger E-box-binding homeobox 1 (ZEB1. Conclusion: In summary, our findings demonstrated that

  20. Prediction of pKa values using the PM6 semiempirical method

    Directory of Open Access Journals (Sweden)

    Jimmy C. Kromann

    2016-08-01

    Full Text Available The PM6 semiempirical method and the dispersion and hydrogen bond-corrected PM6-D3H+ method are used together with the SMD and COSMO continuum solvation models to predict pKa values of pyridines, alcohols, phenols, benzoic acids, carboxylic acids, and phenols using isodesmic reactions and compared to published ab initio results. The pKa values of pyridines, alcohols, phenols, and benzoic acids considered in this study can generally be predicted with PM6 and ab initio methods to within the same overall accuracy, with average mean absolute differences (MADs of 0.6–0.7 pH units. For carboxylic acids, the accuracy (0.7–1.0 pH units is also comparable to ab initio results if a single outlier is removed. For primary, secondary, and tertiary amines the accuracy is, respectively, similar (0.5–0.6, slightly worse (0.5–1.0, and worse (1.0–2.5, provided that di- and tri-ethylamine are used as reference molecules for secondary and tertiary amines. When applied to a drug-like molecule where an empirical pKa predictor exhibits a large (4.9 pH unit error, we find that the errors for PM6-based predictions are roughly the same in magnitude but opposite in sign. As a result, most of the PM6-based methods predict the correct protonation state at physiological pH, while the empirical predictor does not. The computational cost is around 2–5 min per conformer per core processor, making PM6-based pKa prediction computationally efficient enough to be used for high-throughput screening using on the order of 100 core processors.

  1. Thermo-analytical investigations on the superoxides AO{sub 2} (A = K, Rb, Cs), revealing facile access to sesquioxides A{sub 4}O{sub 6}

    Energy Technology Data Exchange (ETDEWEB)

    Merz, Patrick; Schmidt, Marcus; Felser, Claudia [Max-Planck-Institut fuer Chemische Physik fester Stoffe, Dresden (Germany); Jansen, Martin [Max-Planck-Institut fuer Chemische Physik fester Stoffe, Dresden (Germany); Max-Planck-Institut fuer Festkoerperforschung, Stuttgart (Germany)

    2017-04-18

    Rb{sub 4}O{sub 6} and Cs{sub 4}O{sub 6} represent open shell p electron systems, featuring charge, spin, orbital and structural degrees of freedom, which makes them unique candidates for studying the ordering processes related, otherwise exclusively encountered in transition metal based materials. Probing the physical responses has been restrained by the intricacy of synthesizing appropriate amounts of phase pure samples. Tracing the thermal decomposition of respective superoxides has revealed that at least the rubidium and cesium sesquioxides exist in thermodynamic equilibrium, appropriate p-T conditions given. These insights have paved the way to highly efficient and convenient access to Rb{sub 4}O{sub 6} and Cs{sub 4}O{sub 6}. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  2. Glioblastoma with Oligodendroglioma Component (GBMO in an adolescent: a case report

    Directory of Open Access Journals (Sweden)

    Amanda Lopes Maia Rodrigues

    2018-06-01

    Full Text Available Background:Glioblastoma with oligodendroglioma component (GBMO is a recently classified subtype of glioblastoma, which carries different clinical and prognostic outcomes, being frequently misdiagnosed. Both glioblastoma and GBMO are mainly seen in older ages, such as the 5th and 6th decades of life, being an extremely rare occurrence in children or adolescents and more frequent in male patients.  Case report: A 15-year-old girl, presented with history of daily headache, not relieved by painkillers, vomiting, blurred vision and strabismus. Magnetic resonance imaging of the brain revealed expansive tumour on left temporo-occipital lobe. Patient was submitted to intracranial exeresis, along with histopathological examination: glial neoplasm with areas of pleomorphism, hyperchromatism, anaplasia, foci of oligodendroglial component, perinuclear halo and ramified capillaries, resembling oligodendroglioma, necrosis and intense mitotic activity. The immunohistochemical analysis revealed positive Glial Fibrillary Acidic Protein (GFAP, synaptophysin, Ki-67 (MindBomb E3 ubiquitin protein ligase 1 – MIB-1and hyperexpression of Epidermal Growth Factor Receptor (EGFR, indicating GBMO. Subsequently, Fluorescence in situ Hybridization (FISH showed 1p/19q codeletion and Isocitrate Dehydrogenase 1 (IDH 1 mutation, suggesting an oligodendroglioma component. Tumour resection was total and symptoms disappeared. Afterwards, she started adjuvant oral chemotherapy with temozolomide. Treatment was completed nine months after the diagnosis, with no greater symptoms or complications and complete remission.  Conclusion: GBMO must be considered as a possible diagnosis when confronted with a malignant glioma with oligodendroglial tumour component, independent of age or genre. Necrosis upon histopathological examination has a strong relation to shorter median overall survival. IDH mutation and 1p/19q codeletion should be analyzed by immunohistochemistry

  3. REVIEW ON CONSTRUCTION PROJECT MANAGEMENT SOFTWARE PRIMAVERA P6

    OpenAIRE

    Piyush Pramod Bagade* & Prof. Abhijit Bhirud

    2018-01-01

    Planning, scheduling and Resource levelling plays an important role in any construction project maybe it is construction of building or construction of road. In absence of proper planning, scheduling and resource levelling construction industry does not get profit over the project. For this purpose, proper software’s and techniques must be utilize. This paper is focussing on the advantages of Oracle Primavera P6 Software. The latest version of Primavera is P6-17. In any construction work huge...

  4. P53- and mevalonate pathway–driven malignancies require Arf6 for metastasis and drug resistance

    Science.gov (United States)

    Hashimoto, Ari; Oikawa, Tsukasa; Hashimoto, Shigeru; Sugino, Hirokazu; Yoshikawa, Ayumu; Otsuka, Yutaro; Handa, Haruka; Onodera, Yasuhito; Nam, Jin-Min; Oneyama, Chitose; Okada, Masato; Fukuda, Mitsunori

    2016-01-01

    Drug resistance, metastasis, and a mesenchymal transcriptional program are central features of aggressive breast tumors. The GTPase Arf6, often overexpressed in tumors, is critical to promote epithelial–mesenchymal transition and invasiveness. The metabolic mevalonate pathway (MVP) is associated with tumor invasiveness and known to prenylate proteins, but which prenylated proteins are critical for MVP-driven cancers is unknown. We show here that MVP requires the Arf6-dependent mesenchymal program. The MVP enzyme geranylgeranyl transferase II (GGT-II) and its substrate Rab11b are critical for Arf6 trafficking to the plasma membrane, where it is activated by receptor tyrosine kinases. Consistently, mutant p53, which is known to support tumorigenesis via MVP, promotes Arf6 activation via GGT-II and Rab11b. Inhibition of MVP and GGT-II blocked invasion and metastasis and reduced cancer cell resistance against chemotherapy agents, but only in cells overexpressing Arf6 and components of the mesenchymal program. Overexpression of Arf6 and mesenchymal proteins as well as enhanced MVP activity correlated with poor patient survival. These results provide insights into the molecular basis of MVP-driven malignancy. PMID:27044891

  5. New insights into the structure-property relationship of high-voltage electrolyte components for lithium-ion batteries using the pKa value

    International Nuclear Information System (INIS)

    Gallus, Dennis Roman; Wagner, Ralf; Wiemers-Meyer, Simon; Winter, Martin; Cekic-Laskovic, Isidora

    2015-01-01

    In pursuit of higher energy density in lithium-ion batteries (LIBs), a most promising approach focuses on cathode materials that operate at higher potentials and exhibit even higher specific charges than present LIB cathodes charged up to only 3.8 to 4.3 V vs. Li/Li + . To enable a high-voltage (HV) application of the cathode, the “by-materials”, in particular the electrolyte components have to be either thermodynamically or kinetically stable. For this reason, the stability of the electrolyte components towards oxidation, in particular, depending on their HOMO energy levels, is crucial. The theoretical calculation of molecular orbital energies is a helpful and commonly used tool to predict electrochemical stability. Earlier studies demonstrated strong correlation between the HOMO energy and the pK a value, as both depend on electron affinity. Here we report on the first study referring to a pK a value based selection procedure on development of new electrolyte components for the application in lithium-ion batteries. The identified trimethylsilyl(TMS)-based additives, which are known to scavenge HF and show sufficient oxidation stability, enable the application of LiNi 1/3 Co 1/3 Mn 1/3 O 2 (NCM) at an increased upper cut-off potential of 4.6 V vs. Li/Li + without severe degradation, leading to a 50% higher energy density. The use of pK a values is a simple, but highly effective methodology to select appropriate electrolyte components and thus helps to identify functional electrolytes beyond the typical trial and error approach or time-consuming theoretical calculations.

  6. Gene profiling of postnatal Mfrprd6 mutant eyes reveals differential accumulation of Prss56, visual cycle and phototransduction mRNAs.

    Directory of Open Access Journals (Sweden)

    Ramani Soundararajan

    Full Text Available Mutations in the membrane frizzled-related protein (MFRP/Mfrp gene, specifically expressed in the retinal pigment epithelium (RPE and ciliary body, cause nanophthalmia or posterior microphthalmia with retinitis pigmentosa in humans, and photoreceptor degeneration in mice. To better understand MFRP function, microarray analysis was performed on eyes of homozygous Mfrprd6 and C57BL/6J mice at postnatal days (P 0 and P14, prior to photoreceptor loss. Data analysis revealed no changes at P0 but significant differences in RPE and retina-specific transcripts at P14, suggesting a postnatal influence of the Mfrprd6 allele. A subset of these transcripts was validated by quantitative real-time PCR (qRT-PCR. In Mfrprd6 eyes, a significant 1.5- to 2.0-fold decrease was observed among transcripts of genes linked to retinal degeneration, including those involved in visual cycle (Rpe65, Lrat, Rgr, phototransduction (Pde6a, Guca1b, Rgs9, and photoreceptor disc morphogenesis (Rpgrip1 and Fscn2. Levels of RPE65 were significantly decreased by 2.0-fold. Transcripts of Prss56, a gene associated with angle-closure glaucoma, posterior microphthalmia and myopia, were increased in Mfrprd6 eyes by 17-fold. Validation by qRT-PCR indicated a 3.5-, 14- and 70-fold accumulation of Prss56 transcripts relative to controls at P7, P14 and P21, respectively. This trend was not observed in other RPE or photoreceptor mutant mouse models with similar disease progression, suggesting that Prss56 upregulation is a specific attribute of the disruption of Mfrp. Prss56 and Glul in situ hybridization directly identified Müller glia in the inner nuclear layer as the cell type expressing Prss56. In summary, the Mfrprd6 allele causes significant postnatal changes in transcript and protein levels in the retina and RPE. The link between Mfrp deficiency and Prss56 up-regulation, together with the genetic association of human MFRP or PRSS56 variants and ocular size, raises the possibility that

  7. Purification and characterization of lignin peroxidases from Penicillium decumbens P6

    Energy Technology Data Exchange (ETDEWEB)

    Yang, J.S.; Yuan, H.L.; Wang, H.X.; Chen, W.X. [China Agricultural University, Beijing (China). College of Biological Science

    2005-06-01

    Peroxidases are essential enzymes in biodegradation of lignin and lignite which have been investigated intensively in the white-rot fungi. This is the first report of purification and characterization of lignin peroxidase from Penicillium sp. P6 as lignite degradation fungus. The results indicated that the lignin peroxidase of Penicillium decumbens P6 had physical and chemical properties and a N-terminal amino acid sequence different from the lignin peroxidases of white-rot fungi. The lignin peroxidase was isolated from a liquid culture of P. decumbens P6. This enzyme had a molecular weight of 46.3 KDa in SDS-PAGE and exhibited greater activity, temperature stability and wider pH range than those previously reported. The isolation procedure involved (NH{sub 4}){sub 2}SO{sub 4} precipitation, ion-exchange chromatography on DEAE-cellulose and CM-cellulose, gel filtration on Sephadex G-100, and non-denaturing, discontinuous polyacrylamide gel electrophoresis. The K{sub m} and V{sub max} values of this enzyme using veratryl alcohol as substrate were 0.565 mmol L{sup -1} and 0.088 mmol (mg protein){sup -1} min{sup -1} respectively. The optimum pH of P6 lignin peroxidase was 4.0, and 70.6% of the relative activity was remained at pH 9.0. The optimum temperature of the enzyme was 45{sup o}C.

  8. Identification of the 15FRFG domain in HIV-1 Gag p6 essential for Vpr packaging into the virion

    Directory of Open Access Journals (Sweden)

    Zhu Henghu

    2004-09-01

    Full Text Available Abstract The auxiliary regulatory protein Vpr of HIV-1 is packaged in the virion through interaction with the Gag C-terminal p6 domain. Virion packaging of Vpr is critical for Vpr to exert functions in the HIV-1 life cycle. Previous studies suggest that Vpr interacts with a (Lxx4 domain in p6 for virion packaging. In the present study, mutational analysis of HIV-1 Gag p6 domain was performed in the context of the HIV-1 genome to examine the effect on virion packaging of Vpr. Surprisingly, Ala substitutions for Leu44 and Phe45 in the (Lxx4 domain or deletion of the whole (Lxx4 domain (amino acid #35–52 of the Gag p6 domain did not affect Vpr virion packaging. Vpr virion packaging was normal when amino acid #1–23 of the Gag p6 domain was preserved. Most importantly, Ala substitutions for Phe15, Arg16 and Phe17 in the context of amino acid #1–23 of the Gag p6 domain abolished Vpr virion packaging. Single Ala substitutions for Phe15 and Phe17 also abolished Vpr virion packaging, whereas Ala substitution for Arg16 had no effect. Our studies have revealed a novel signal sequence for Vpr packaging into the HIV-1 virion. The 15FRFG domain in p6 resembles the FxFG repeat sequences commonly found in proteins of the nuclear pore complex. These results have provided novel insights into the process of virion packaging of Vpr and suggest for the first time that Vpr may recognize the FxFG domain for both virion packaging and association with nuclear pores.

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

    Science.gov (United States)

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

    2015-03-01

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

  10. Investigation of plasma arc welding as a method for the additive manufacturing of titanium-(6)aluminum-(4)vanadium alloy components

    Science.gov (United States)

    Stavinoha, Joe N.

    The process of producing near net-shape components by material deposition is known as additive manufacturing. All additive manufacturing processes are based on the addition of material with the main driving forces being cost reduction and flexibility in both manufacturing and product design. With wire metal deposition, metal is deposited as beads side-by-side and layer-by-layer in a desired pattern to build a complete component or add features on a part. There are minimal waste products, low consumables, and an efficient use of energy and feedstock associated with additive manufacturing processes. Titanium and titanium alloys are useful engineering materials that possess an extraordinary combination of properties. Some of the properties that make titanium advantageous for structural applications are its high strength-to-weight ratio, low density, low coefficient of thermal expansion, and good corrosion resistance. The most commonly used titanium alloy, Ti-6Al-4V, is typically used in aerospace applications, pressure vessels, aircraft gas turbine disks, cases and compressor blades, and surgical implants. Because of the high material prices associated with titanium alloys, the production of near net-shape components by additive manufacturing is an attractive option for the manufacturing of Ti-6Al-4V alloy components. In this thesis, the manufacturing of cylindrical Ti-6Al-4V alloy specimens by wire metal deposition utilizing the plasma arc welding process was demonstrated. Plasma arc welding is a cost effective additive manufacturing technique when compared to other current additive manufacturing methods such as laser beam welding and electron beam welding. Plasma arc welding is considered a high-energy-density welding processes which is desirable for the successful welding of titanium. Metal deposition was performed using a constant current plasma arc welding power supply, flow-purged welding chamber, argon shielding and orifice gas, ERTi-5 filler metal, and Ti-6Al

  11. Subtype-specific, bi-component inhibition of SK channels by low internal pH

    DEFF Research Database (Denmark)

    Peitersen, Torben; Jespersen, Thomas; Jorgensen, Nanna K

    2006-01-01

    The effects of low intracellular pH (pH(i) 6.4) on cloned small-conductance Ca2+-activated K+ channel currents of all three subtypes (SK1, SK2, and SK3) were investigated in HEK293 cells using the patch-clamp technique. In 400 nM internal Ca2+ [Ca2+]i, all subtypes were inhibited by pH(i) 6...

  12. Identification of promoter polymorphisms in the cytochrome P450 CYP6AY1 linked with insecticide resistance in the brown planthopper, Nilaparvata lugens.

    Science.gov (United States)

    Pang, R; Li, Y; Dong, Y; Liang, Z; Zhang, Y; Zhang, W

    2014-12-01

    Imidacloprid resistance in the brown planthopper, Nilaparvata lugens, is primarily the result of the over-expression of cytochrome P450 monooxygenases. Here, a field-collected strain of N. lugens was shown to be highly resistant to both imidacloprid and buprofezin. Insecticide exposure and quantitative real-time PCR revealed that its resistance was mainly associated with a cytochrome P450 gene, CYP6AY1. CYP6AY1 is known to metabolize imidacloprid but its effect on buprofezin is unclear. In the 5'-untranslated region of CYP6AY1, a novel alternative splicing was detected. After a 1990-bp promoter region was cloned, its basal luciferase activity was assessed. Furthermore, genotyping studies identified 12 variations in the promoter region that discriminated between the field-collected and control strain. Finally, survival bioassays revealed a single nucleotide polymorphism and an insertion-deletion polymorphism linked to buprofezin and imidacloprid resistance. Mutagenesis of these sites enhanced the promoter activity of CYP6AY1. These results suggest that promoter polymorphisms may affect P450-mediated multiple insecticide resistance of pests. © 2014 The Royal Entomological Society.

  13. GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests shared genetic susceptibility with diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Smedby, Karin E; Foo, Jia Nee; Skibola, Christine F

    2011-01-01

    Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated w...

  14. Prediction of dissolved reactive phosphorus losses from small agricultural catchments: calibration and validation of a parsimonious model

    Directory of Open Access Journals (Sweden)

    C. Hahn

    2013-10-01

    Full Text Available Eutrophication of surface waters due to diffuse phosphorus (P losses continues to be a severe water quality problem worldwide, causing the loss of ecosystem functions of the respective water bodies. Phosphorus in runoff often originates from a small fraction of a catchment only. Targeting mitigation measures to these critical source areas (CSAs is expected to be most efficient and cost-effective, but requires suitable tools. Here we investigated the capability of the parsimonious Rainfall-Runoff-Phosphorus (RRP model to identify CSAs in grassland-dominated catchments based on readily available soil and topographic data. After simultaneous calibration on runoff data from four small hilly catchments on the Swiss Plateau, the model was validated on a different catchment in the same region without further calibration. The RRP model adequately simulated the discharge and dissolved reactive P (DRP export from the validation catchment. Sensitivity analysis showed that the model predictions were robust with respect to the classification of soils into "poorly drained" and "well drained", based on the available soil map. Comparing spatial hydrological model predictions with field data from the validation catchment provided further evidence that the assumptions underlying the model are valid and that the model adequately accounts for the dominant P export processes in the target region. Thus, the parsimonious RRP model is a valuable tool that can be used to determine CSAs. Despite the considerable predictive uncertainty regarding the spatial extent of CSAs, the RRP can provide guidance for the implementation of mitigation measures. The model helps to identify those parts of a catchment where high DRP losses are expected or can be excluded with high confidence. Legacy P was predicted to be the dominant source for DRP losses and thus, in combination with hydrologic active areas, a high risk for water quality.

  15. Effect of three 2-allyl-p-mentha-6,8-dien-2-ols on inhibition of mild steel corrosion in 1 M HCl

    Directory of Open Access Journals (Sweden)

    S. Kharchouf

    2014-11-01

    Full Text Available 2-Allyl-p-mentha-6,8-dien-2-ols P1−P3 synthesized from carvone P are tested as corrosion inhibitors of steel in 1 M HCl using weight loss measurements, potentiodynamic polarisation and impedance spectroscopy (EIS methods. The addition of 2-allyl-p-mentha-6,8-dien-2-ols reduced the corrosion rate. Potentiodynamic polarisation studies clearly reveal that the presence of inhibitors does not change the mechanism of hydrogen evolution and that they act essentially as cathodic inhibitors. 2-Allyl-p-mentha-6,8-dien-2-ols tested adsorb on the steel surface according to Langmuir isotherm. From the adsorption isotherm some thermodynamic data for the adsorption process are calculated and discussed. EIS measurements show the increase of the charge-transfer resistance with the inhibitor concentration. The highest inhibition efficiency (92% is obtained for P1 at 3 g/L. The corrosion rate decreases with the rise of temperature. The corresponding activation energies are determined.

  16. LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase.

    OpenAIRE

    Manns, M P; Griffin, K J; Sullivan, K F; Johnson, E F

    1991-01-01

    LKM-1 autoantibodies, which are associated with autoimmune chronic active hepatitis, recognize P450IID6, a cytochrome P-450 monooxygenase. The reactivities of 26 LKM-1 antisera were tested with a panel of deletion mutants of P450IID6 expressed in Escherichia coli. 22 sera recognize a 33-amino acid segment of P450IID6, and 11 of these recognize a shorter segment, DPAQPPRD. PAQPPR is also found in IE175 of herpes simplex virus type 1 (HSV-1). Antibodies for HSV-1 proteins were detected by ELISA...

  17. High-quality MOVPE butt-joint integration of InP/AlGaInAs/InGaAsP-based all-active optical components

    DEFF Research Database (Denmark)

    Kulkova, Irina; Kadkhodazadeh, Shima; Kuznetsova, Nadezda

    2014-01-01

    In this paper, we demonstrate the applicability of MOVPE butt-joint regrowth for integration of all-active InP/AlGaAs/InGaAsP optical components and the realization of high-functionality compact photonic devices. Planar high-quality integration of semiconductor optical amplifiers of various epi...

  18. P300 component of event-related potentials in persons with asperger disorder.

    Science.gov (United States)

    Iwanami, Akira; Okajima, Yuka; Ota, Haruhisa; Tani, Masayuki; Yamada, Takashi; Yamagata, Bun; Hashimoto, Ryuichiro; Kanai, Chieko; Takashio, Osamu; Inamoto, Atsuko; Ono, Taisei; Takayama, Yukiko; Kato, Nobumasa

    2014-10-01

    In the present study, we investigated auditory event-related potentials in adults with Asperger disorder and normal controls using an auditory oddball task and a novelty oddball task. Task performance and the latencies of P300 evoked by both target and novel stimuli in the two tasks did not differ between the two groups. Analysis of variance revealed that there was a significant interaction effect between group and electrode site on the mean amplitude of the P300 evoked by novel stimuli, which indicated that there was an altered distribution of the P300 in persons with Asperger disorder. In contrast, there was no significant interaction effect on the mean P300 amplitude elicited by target stimuli. Considering that P300 comprises two main subcomponents, frontal-central-dominant P3a and parietal-dominant P3b, our results suggested that persons with Asperger disorder have enhanced amplitude of P3a, which indicated activated prefrontal function in this task.

  19. Prostate Cancer Diagnosed After Repeat Biopsies Have a Favorable Pathological Outcome but Similar Recurrence Rate

    Science.gov (United States)

    Lopez-Corona, Ernesto; Ohori, Makoto; Wheeler, Thomas M.; Reuter, Victor E.; Scardino, Peter T.; Kattan, Michael W.; Eastham, James A.

    2007-01-01

    Purpose We investigated whether repeat prostate biopsies are associated with more favorable prognoses, less extensive disease or higher rates of IC in patients who are ultimately diagnosed with prostate cancer and treated with RRP. Materials and Methods We examined standard clinical and pathological data on 1,357 patients treated with RRP from 1983 to 2001. In addition, we noted the rate of IC in a subgroup of 847 patients in whom tumor volume was measured. Results Cancer was found in 1,042 patients (77%) at the first biopsy, in 227 (17%) at the second biopsy, in 59 (4%) at the third biopsy and in 29 (2%) at the fourth or later biopsy. Patients with 2 or greater biopsies had a higher rate of clinical T1c stage cancer and larger prostates than patients with only 1 biopsy (each p <0.0001). After RRP patients with 1 biopsy had a lower rate of organ confined tumors (61% vs 75%, p <0.0001), and a higher rate of extracapsular extension, seminal vesicle invasion, lymph node metastases and Gleason sum 7 or greater than other patients. IC was found in 10% of patients with 1 biopsy and 18% of those with 2 or greater biopsies (p = 0.018). Despite these more favorable pathological outcomes there was no difference in biochemical recurrence rate. Conclusions Although we found that a greater number of biopsies was related to a better pathological outcome after RRP, the number of biopsies did not predict disease recurrence. The increasing number of biopsies currently being performed, especially in patients with larger prostates, likely results in higher rates of IC. PMID:16469581

  20. Proteome-metabolome profiling of ovarian cancer ascites reveals novel components involved in intercellular communication.

    Science.gov (United States)

    Shender, Victoria O; Pavlyukov, Marat S; Ziganshin, Rustam H; Arapidi, Georgij P; Kovalchuk, Sergey I; Anikanov, Nikolay A; Altukhov, Ilya A; Alexeev, Dmitry G; Butenko, Ivan O; Shavarda, Alexey L; Khomyakova, Elena B; Evtushenko, Evgeniy; Ashrafyan, Lev A; Antonova, Irina B; Kuznetcov, Igor N; Gorbachev, Alexey Yu; Shakhparonov, Mikhail I; Govorun, Vadim M

    2014-12-01

    Ovarian cancer ascites is a native medium for cancer cells that allows investigation of their secretome in a natural environment. This medium is of interest as a promising source of potential biomarkers, and also as a medium for cell-cell communication. The aim of this study was to elucidate specific features of the malignant ascites metabolome and proteome. In order to omit components of the systemic response to ascites formation, we compared malignant ascites with cirrhosis ascites. Metabolome analysis revealed 41 components that differed significantly between malignant and cirrhosis ascites. Most of the identified cancer-specific metabolites are known to be important signaling molecules. Proteomic analysis identified 2096 and 1855 proteins in the ovarian cancer and cirrhosis ascites, respectively; 424 proteins were specific for the malignant ascites. Functional analysis of the proteome demonstrated that the major differences between cirrhosis and malignant ascites were observed for the cluster of spliceosomal proteins. Additionally, we demonstrate that several splicing RNAs were exclusively detected in malignant ascites, where they probably existed within protein complexes. This result was confirmed in vitro using an ovarian cancer cell line. Identification of spliceosomal proteins and RNAs in an extracellular medium is of particular interest; the finding suggests that they might play a role in the communication between cancer cells. In addition, malignant ascites contains a high number of exosomes that are known to play an important role in signal transduction. Thus our study reveals the specific features of malignant ascites that are associated with its function as a medium of intercellular communication. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Alignment creation in atomic ensembles by elastic electron scattering; the case of 138Ba(...6s6p 1P1) atoms

    International Nuclear Information System (INIS)

    Trajmar, S.; Kanik, I.; LeClair, L.R.; Khakoo, M.A.; Bray, I.; Fursa, D.; Csanak, G.

    1998-01-01

    We describe some of our results from a joint experimental and theoretical program concerning elastic electron scattering by 138 Ba(...6s6p 1 P 1 ) atoms. From the experimental results, we derived various scattering parameters and magnetic sublevel specific differential elastic scattering cross sections at impact energy (E 0 ) of 20.0 eV and at scattering angles (θ) of 10deg, 15deg, and 20deg. The same parameters and cross sections were calculated by the convergent close coupling (CCC) approximation and compared to the experimental results. An excellent agreement, found for the two sets of data, gave us confidence in the CCC method and allowed us to extend the angular and energy ranges for the purpose of generating integral elastic scattering cross sections needed for the deduction of the alignment creation cross sections. (J.P.N.)

  2. Individual whey protein components influence lipid oxidation dependent on pH

    DEFF Research Database (Denmark)

    Horn, Anna Frisenfeldt; Nielsen, Nina Skall; Jacobsen, Charlotte

    In emulsions, lipid oxidation is expected to be initiated at the oil-water interface. The properties of the emulsifier used and the composition at the interface is therefore expected to be of great importance for the resulting oxidation. Previous studies have shown that individual whey protein...... by affecting the preferential adsorption of whey protein components at the interface. The aim of the study was to compare lipid oxidation in 10% fish oil-in-water emulsions prepared with 1% whey protein having either a high concentration of α-lactalbumin, a high concentration of β-lactoglobulin or equal...... amounts of the two. Emulsions were prepared at pH4 and pH7. Emulsions were characterized by their droplet sizes, viscosities, and contents of proteins in the water phase. Lipid oxidation was assessed by PV and secondary volatile oxidation products. Results showed that pH greatly influenced the oxidative...

  3. In vivo intracellular pH measurements in tobacco and Arabidopsis reveal an unexpected pH gradient in the endomembrane system.

    Science.gov (United States)

    Martinière, Alexandre; Bassil, Elias; Jublanc, Elodie; Alcon, Carine; Reguera, Maria; Sentenac, Hervé; Blumwald, Eduardo; Paris, Nadine

    2013-10-01

    The pH homeostasis of endomembranes is essential for cellular functions. In order to provide direct pH measurements in the endomembrane system lumen, we targeted genetically encoded ratiometric pH sensors to the cytosol, the endoplasmic reticulum, and the trans-Golgi, or the compartments labeled by the vacuolar sorting receptor (VSR), which includes the trans-Golgi network and prevacuoles. Using noninvasive live-cell imaging to measure pH, we show that a gradual acidification from the endoplasmic reticulum to the lytic vacuole exists, in both tobacco (Nicotiana tabacum) epidermal (ΔpH -1.5) and Arabidopsis thaliana root cells (ΔpH -2.1). The average pH in VSR compartments was intermediate between that of the trans-Golgi and the vacuole. Combining pH measurements with in vivo colocalization experiments, we found that the trans-Golgi network had an acidic pH of 6.1, while the prevacuole and late prevacuole were both more alkaline, with pH of 6.6 and 7.1, respectively. We also showed that endosomal pH, and subsequently vacuolar trafficking of soluble proteins, requires both vacuolar-type H(+) ATPase-dependent acidification as well as proton efflux mediated at least by the activity of endosomal sodium/proton NHX-type antiporters.

  4. Inter-ring rotations of AAA ATPase p97 revealed by electron cryomicroscopy.

    Science.gov (United States)

    Yeung, Heidi O; Förster, Andreas; Bebeacua, Cecilia; Niwa, Hajime; Ewens, Caroline; McKeown, Ciarán; Zhang, Xiaodong; Freemont, Paul S

    2014-03-05

    The type II AAA+ protein p97 is involved in numerous cellular activities, including endoplasmic reticulum-associated degradation, transcription activation, membrane fusion and cell-cycle control. These activities are at least in part regulated by the ubiquitin system, in which p97 is thought to target ubiquitylated protein substrates within macromolecular complexes and assist in their extraction or disassembly. Although ATPase activity is essential for p97 function, little is known about how ATP binding or hydrolysis is coupled with p97 conformational changes and substrate remodelling. Here, we have used single-particle electron cryomicroscopy (cryo-EM) to study the effect of nucleotides on p97 conformation. We have identified conformational heterogeneity within the cryo-EM datasets from which we have resolved two major p97 conformations. A comparison of conformations reveals inter-ring rotations upon nucleotide binding and hydrolysis that may be linked to the remodelling of target protein complexes.

  5. Measurement of A and A/sub nn/ in p + pp + p at 6 GeV/c

    International Nuclear Information System (INIS)

    Crosbie, E.A.; Ratner, L.G.; Schultz, P.F.

    1980-01-01

    Previous measurements of the 6 GeV/c p - p elastic scattering rates have been extended with beam and target polarizations normal to the scattering plane. Improvements to the measuring technique include additional momentum resolution added to the recoil arm and increased solid angle resulting from two-element hodoscopes. Beam intensity was increased by a factor of 3 and additional shielding was installed. Along with the usual statistical uncertainty and errors in measurement of the target polarization, a term was added in quadrature due to a systematic difference between target and beam asymmetries (A/sub T/ and A/sub B/)

  6. Characterization of additional components of the environmental pH-sensing complex in the pathogenic fungus Cryptococcus neoformans.

    Science.gov (United States)

    Pianalto, Kaila M; Ost, Kyla S; Brown, Hannah E; Alspaugh, J Andrew

    2018-05-16

    Pathogenic microorganisms must adapt to changes in their immediate surroundings, including alterations in pH, to survive the shift from the external environment to that of the infected host. In the basidiomycete fungal pathogen Cryptococcus neoformans , these pH changes are primarily sensed by the fungal-specific, alkaline pH-sensing Rim/Pal pathway. The C. neoformans Rim pathway has diverged significantly from that described in ascomycete fungi. We recently identified the C. neoformans putative pH sensor Rra1, which activates the Rim pathway in response to elevated pH. In this study, we probed the function of Rra1 by analyzing its cellular localization and performing protein co-immunoprecipitation to identify potential Rra1 interactors. We found that Rra1 does not strongly colocalize or interact with immediate downstream Rim pathway components. However, these experiments identified a novel Rra1 interactor, the previously uncharacterized C. neoformans nucleosome assembly protein 1 (Nap1), which was required for Rim pathway activation. We observed that Nap1 specifically binds to the C-terminal tail of the Rra1 sensor, likely promoting Rra1 protein stability. This function of Nap1 is conserved in fungi closely related to C. neoformans that contain Rra1 orthologs, but not in the more distantly-related ascomycete fungus Saccharomyces cerevisiae In conclusion, our findings have revealed the sophisticated, yet distinct, molecular mechanisms by which closely and distantly related microbial phyla rapidly adapt to environmental signals and changes such as alterations in pH. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Septic wastewater treatment using recycled rubber particles as biofiltration media.

    Science.gov (United States)

    Oh, Jin Hwan; Park, Jaeyoung; Ellis, Timothy G

    2014-01-01

    Performance of the laboratory-scale recycled rubber particles (RRP) biofilter was compared to a conventional gravel system and a peat biofilter for treatment of septic tank effluent. During the study, the RRP biofilter provided similar or better performance than other systems in terms of organic removal and hydraulic capacity. After the start-up period, RRP biofilter achieved removal efficiencies for BOD5, total suspended solids (TSS), ammonia nitrogen of 96%, 93%, and 90%, respectively, over the range of hydraulic loading rates of 57-204 L/m2/d. On the other hand, the peat biofilter failed hydraulically and the gravel system showed high TSS concentrations in the effluent. RRP provided high surface area and sufficient time for biological treatment. In addition, RRP was observed to provide ammonia adsorption capacity. The results showed that RRP has the potential to be used as substitutes for natural aggregate such as gravel in septic system drainfields. The RRP biofilter can be used as alternative septic systems for the sites where an existing septic system has failed or site conditions, such as high groundwater table or small lot size, are not suitable for the installation of conventional septic systems.

  8. Feasibility analysis of modified AL-6XN steel for structure component application in supercritical water-cooled reactor

    Institute of Scientific and Technical Information of China (English)

    Xinggang LI; Qingzhi YAN; Rong MA; Haoqiang WANG; Changchun GE

    2009-01-01

    Modified AL-6XN austenite steel was patterned after AL-6XN superaustenitic stainless steel by introducing microalloy elements such as zirconium and titanium in order to adapt to recrystallizing thermo-mechanical treatment and further improve crevice corrosion resistance. Modified AL-6XN exhibited comparable tensile strength, and superior plasticity and impact toughness to commercial AL-6XN steel. The effects of aging behavior on corrosion resistance and impact toughness were measured to evaluate the qualification of modified AL-6XN steel as an in-core component and cladding material in a supercritical water-cooled reactor. Attention should be paid to degradation in corrosion resistance and impact toughness after aging for 50 hours when modified AL-6XN steel is considered as one of the candidate materials for in-core components and cladding tubes in supercritical water-cooled reactors.

  9. In silico binding affinity studies of N-9 substituted 6-(4-(4-propoxyphenylpiperazin-1-yl-9H-purine derivatives-Target for P70-S6K1 & PI3K-δ kinases

    Directory of Open Access Journals (Sweden)

    Manjunath G. Sunagar

    2018-03-01

    Full Text Available P70-S6K1 & PI3K-δ kinases are identified to be involved in many physiological processes associated with cancer, therefore many of the inhibitors being designed to target these kinases are in clinical trials. In the current study we have exploited the N-9 substituted 6-(4-(4-propoxyphenyl piperazin-1-yl-9H-purine derivatives for their inhibitory properties with the above kinases. We have used an in silico docking study with seventeen purine derivatives for their binding affinity calculations. The binding affinities of these small molecules with P70-S6K1 & PI3K-δ were performed using AutoDock Vina. Among all the compounds, PP16 showed highest binding affinity of −14.7 kcal/mol with P70-S6K1 kinase & −17.2 kcal/mol with PI3K-δ kinases as compared to the molecules under clinical trials (PF-4708671 & IC-87114. Docking studies revealed that N-9 coumarine substituted purine derivative could be one of the potential ligands for the inhibition of P70-S6K1 & PI3K-δ kinases. Hence, this compound can be further investigated by in vitro and in vivo experiments for further validation.

  10. Structural organizations of yeast RNase P and RNase MRP holoenzymes as revealed by UV-crosslinking studies of RNA-protein interactions.

    Science.gov (United States)

    Khanova, Elena; Esakova, Olga; Perederina, Anna; Berezin, Igor; Krasilnikov, Andrey S

    2012-04-01

    Eukaryotic ribonuclease (RNase) P and RNase MRP are closely related ribonucleoprotein complexes involved in the metabolism of various RNA molecules including tRNA, rRNA, and some mRNAs. While evolutionarily related to bacterial RNase P, eukaryotic enzymes of the RNase P/MRP family are much more complex. Saccharomyces cerevisiae RNase P consists of a catalytic RNA component and nine essential proteins; yeast RNase MRP has an RNA component resembling that in RNase P and 10 essential proteins, most of which are shared with RNase P. The structural organizations of eukaryotic RNases P/MRP are not clear. Here we present the results of RNA-protein UV crosslinking studies performed on RNase P and RNase MRP holoenzymes isolated from yeast. The results indicate locations of specific protein-binding sites in the RNA components of RNase P and RNase MRP and shed light on the structural organizations of these large ribonucleoprotein complexes.

  11. Anion exchange chromatography of 99mTc(Sn)-EHDP complexes: determination of the charge of the components and influence of pH and ligand concentration

    International Nuclear Information System (INIS)

    Huigen, Y.M.; Diender, M.; Gelsema, W.J.; De Ligny, C.L.

    1991-01-01

    The components of a 99m Tc(Sn)-EHDP complex mixture were separated by means of normal pressure and high-pressure anion exchange chromatography. Precautions were taken to prevent the dissociation of the complexes during chromatography. The charges of the components were determined according to the methods of Wilson and Pinkerton (1985) and Russell and Bischoff (1985). The values of the charges obtained with the two methods are not in agreement. Russell and Bischoff's method, in which a reference ion is used, must be preferred. However, even with this method the accuracy of the data obtained is probably limited, due to the difficulty of making corrections for activity coefficients of highly-charge ions at the rather high electrolyte concentrations that must be used in the ion exchange method. So, we think that it is only warranted to conclude that the mean charge of the components of 99m Tc(Sn)-EHDP is about -6 at pH 7, and that the charges of the individual components are in the range of -4 to -9. The influence of pH and ligand concentration in the reaction mixture was determined with high pressure anion exchange chromatography. It was found that a decrease in the pH of the reaction mixture favours the production of complexes with a long retention time, which leads to a slightly higher mean charge. The ligand concentration of the reaction mixture scarcely influenced the relative concentrations of the components. (author)

  12. Revealing the microstructure of the giant component in random graph ensembles

    Science.gov (United States)

    Tishby, Ido; Biham, Ofer; Katzav, Eytan; Kühn, Reimer

    2018-04-01

    The microstructure of the giant component of the Erdős-Rényi network and other configuration model networks is analyzed using generating function methods. While configuration model networks are uncorrelated, the giant component exhibits a degree distribution which is different from the overall degree distribution of the network and includes degree-degree correlations of all orders. We present exact analytical results for the degree distributions as well as higher-order degree-degree correlations on the giant components of configuration model networks. We show that the degree-degree correlations are essential for the integrity of the giant component, in the sense that the degree distribution alone cannot guarantee that it will consist of a single connected component. To demonstrate the importance and broad applicability of these results, we apply them to the study of the distribution of shortest path lengths on the giant component, percolation on the giant component, and spectra of sparse matrices defined on the giant component. We show that by using the degree distribution on the giant component one obtains high quality results for these properties, which can be further improved by taking the degree-degree correlations into account. This suggests that many existing methods, currently used for the analysis of the whole network, can be adapted in a straightforward fashion to yield results conditioned on the giant component.

  13. Office-based Management of Recurrent Respiratory Papilloma.

    Science.gov (United States)

    Motz, Kevin M; Hillel, Alexander T

    2016-06-01

    This review will highlight the indications and benefits of office-based therapy for recurrent respiratory papillomatosis (RRP) and discuss the utilization of photo-dynamic lasers and adjuvant medical therapy in office-based settings. Office-based management of RRP allows for more timely interventions, is preferred by the majority of patients, and negates the risk of general anesthesia. Current literature argues for the utilization of KTP laser over CO 2 laser for office-based treatment of RRP. Medical therapies for RRP are limited, but agents such as bevacizumab are promising and have been shown to reduce disease burden. Medical therapies that can induce disease remission are still needed. Office-based procedures save time and healthcare expenses compared to like procedures in the operating room. However, the increased frequency for office-based procedures predicts similar overall healthcare costs for office-based and OR laser excision of RRP. Office-based management of RRP is a feasible and well-tolerated strategy in appropriately selected patients with adequate local anesthesia.

  14. Biometric relationships of ocular components in esotropic amblyopia

    Directory of Open Access Journals (Sweden)

    Iara Debert

    2012-02-01

    Full Text Available PURPOSE: To investigate the contribution of the individual ocular components, i.e. anterior chamber depth, lens thickness and vitreous chamber depth, to total axial length in patients with esotropic amblyopia. METHODS: The study population consisted of 74 children, aged between 5 and 8 years: thirty-seven patients with esotropic amblyopia and 37 healthy volunteers (control group. The participants underwent a comprehensive ophthalmological examination, including cycloplegic refraction and A-scan ultrasonography. Anterior chamber depth, lens thickness, vitreous chamber depth and total axial length were recorded. Paired Student's t-tests were used to compare biometric measurements between amblyopic eyes and their fellow eyes and between right and left eyes in the control group. To evaluate the contribution of the ocular components to the total axial length, we report the individual components as a percentage of total axial length. RESULTS: The comparison between amblyopic and fellow eyes regarding the individual contribution from ocular components to the total axial length revealed greater contribution from lens thickness (P=0.001 and smaller contribution from vitreous chamber depth (P=0.001 in amblyopic eyes, despite similar contribution from anterior chamber depth (P=0.434. The comparison between right and left eyes in the control group showed similar contributions from anterior chamber depth (P=0.620, lens thickness (P=0.721, and vitreous chamber depth (P=0.483. CONCLUSIONS: This study shows differences between amblyopic and non-amblyopic eyes when the total axial length is broken down into the individual contribution from the ocular components.

  15. Nuclear surveillance of mRNP formation

    DEFF Research Database (Denmark)

    Jensen, Torben Heick

    Proper formation of mRNP requires co-transcriptional loading of proteins onto nascent transcripts. Mutations in several genes involved in mRNA processing, mRNP assembly and nuclear export lead to production of aberrant mRNPs that are retained in transcription site-associated foci. Retention...... and degradation of transcripts depend on the nuclear exosome of 3’-5’ exonucleases.We have studied connections between mRNP assembly and quality control in the yeast S. cerevisiae using mutants of the THO complex. THO is implicated in co-transcriptional mRNP assembly, but its precise role is not known. Genetic...... and biochemical data now show that a defective THO complex negatively impacts mRNA 3’-end processing. We are currently trying to understand the relationship between this phenomenon and mRNP quality control. Retention of mRNP in THO mutants is dependent on the nuclear exosome component Rrp6p. Using the solved...

  16. Heat-equilibrium low-temperature plasma decay in synthesis of ammonia via transient components N2H6

    International Nuclear Information System (INIS)

    Cao Guobin; Song Youqun; Chen Qing; Zhou Qiulan; Cao Yun; Wang Chunhe

    2001-01-01

    The author introduced a new method of heat-equilibrium low-temperature plasma in ammonia synthesis and a technique of continuous real-time inlet sampling mass-spectrometry to detect the reaction channel and step of the decay of transient component N 2 H 6 into ammonia. The experimental results indicated that in the process of ammonia synthesis by discharge of N 2 and H 2 mixture, the transient component N 2 H 6 is a necessary step

  17. Aggregation-enhanced emission and piezochromic luminescence of 9,10-bis(p-dibutylaminostyryl)-2,6-bis(p-t-butylstyryl)anthracene

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Mingxiao; Zhang, Deteng; Li, Yiping; Wang, Jianfeng; Gao, Yangyang; Yang, Wenjun, E-mail: ywjph2004@qust.edu.cn

    2014-04-15

    A cruciform 9,10-distyrylanthracene-containing luminogen, 9,10-bis(p-dibutylaminostyryl)-2,6-bis(p-t-butylstyryl)anthracene (DDC), has been synthesized and the optical properties investigated. The results show that DDC is an aggregation-induced enhanced emission (AIEE) and piezofluorochromic (PFC) dye. The fluorescence quantum yield in THF/water=1/9 (18.1%) is about 12-fold over that in THF (1.53%). PFC experiment shows that the fluorescence colors (emission spectra) of DDC solid change reversibly between orange-red (602 nm) and red (632 nm) emissions upon pressing and annealing. Wide-angle X-ray diffraction and differential scanning calorimetric analyses reveal that the grinding has induced the phase transition of DDC solid from pristine crystalline to ground amorphous states, and annealing could cause the re-crystallization of amorphized DDC solid. This transformation between crystalline and amorphous states is responsible for the reversible PFC behavior upon external stimuli. Highlights: • A two-dimensional cross-conjugated luminogen (DDC) was synthesized. • DDC exhibits aggregation-enhanced emission and piezofluorochromic behaviors. • DDC emits bluer light in the crystalline phase than in the amorphous phase. • The PFC mechanism is ascribed to grinding-induced amorphization.

  18. Dynamic Multi-Component Hemiaminal Assembly

    Science.gov (United States)

    You, Lei; Long, S. Reid; Lynch, Vincent M.

    2012-01-01

    A simple approach to generating in situ metal templated tris-(2-picolyl)amine-like multi-component assemblies with potential applications in molecular recognition and sensing is reported. The assembly is based on the reversible covalent association between di-(2-picolyl)amine and aldehydes. Zinc ion is the best for inducing assembly among the metal salts investigated, while 2-picolinaldehyde is the best among the heterocyclic aldehydes studied. Although an equilibrium constant of 6.6 * 103 M-1 was measured for the assembly formed by 2-picolinaldehdye, di-(2-picolyl)amine, and zinc triflate, the equilibrium constants for other systems are in the 102 M-1 range. X-ray structural analysis revealed that zinc adopts a trigonal bipyramidal geometry within the assembled ligand. The diversity and equilibrium of the assemblies are readily altered by simply changing concentrations, varying components, or adding counter anions. PMID:21919095

  19. Biochemical and functional analysis of two Plasmodium falciparum blood-stage 6-cys proteins: P12 and P41.

    Directory of Open Access Journals (Sweden)

    Tana Taechalertpaisarn

    Full Text Available The genomes of Plasmodium parasites that cause malaria in humans, other primates, birds, and rodents all encode multiple 6-cys proteins. Distinct 6-cys protein family members reside on the surface at each extracellular life cycle stage and those on the surface of liver infective and sexual stages have been shown to play important roles in hepatocyte growth and fertilization respectively. However, 6-cys proteins associated with the blood-stage forms of the parasite have no known function. Here we investigate the biochemical nature and function of two blood-stage 6-cys proteins in Plasmodium falciparum, the most pathogenic species to afflict humans. We show that native P12 and P41 form a stable heterodimer on the infective merozoite surface and are secreted following invasion, but could find no evidence that this complex mediates erythrocyte-receptor binding. That P12 and P41 do not appear to have a major role as adhesins to erythrocyte receptors was supported by the observation that antisera to these proteins did not substantially inhibit erythrocyte invasion. To investigate other functional roles for these proteins their genes were successfully disrupted in P. falciparum, however P12 and P41 knockout parasites grew at normal rates in vitro and displayed no other obvious phenotypic changes. It now appears likely that these blood-stage 6-cys proteins operate as a pair and play redundant roles either in erythrocyte invasion or in host-immune interactions.

  20. The genome sequence of the protostome Daphnia pulex encodes respective orthologues of a neurotrophin, a Trk and a p75NTR: Evolution of neurotrophin signaling components and related proteins in the bilateria

    Directory of Open Access Journals (Sweden)

    Wilson Karen HS

    2009-10-01

    Full Text Available Abstract Background Neurotrophins and their Trk and p75NTR receptors play an important role in the nervous system. To date, neurotrophins, Trk and p75NTR have only been found concomitantly in deuterostomes. In protostomes, homologues to either neurotrophin, Trk or p75NTR are reported but their phylogenetic relationship to deuterostome neurotrophin signaling components is unclear. Drosophila has neurotrophin homologues called Spätzles (Spz, some of which were recently renamed neurotrophins, but direct proof that these are deuterostome neurotrophin orthologues is lacking. Trks belong to the receptor tyrosine kinase (RTK family and among RTKs, Trks and RORs are closest related. Flies lack Trks but have ROR and ROR-related proteins called NRKs playing a neurotrophic role. Mollusks have so far the most similar proteins to Trks (Lymnaea Trk and Aplysia Trkl but the exact phylogenetic relationship of mollusk Trks to each other and to vertebrate Trks is unknown. p75NTR belongs to the tumor necrosis factor receptor (TNFR superfamily. The divergence of the TNFR families in vertebrates has been suggested to parallel the emergence of the adaptive immune system. Only one TNFR representative, the Drosophila Wengen, has been found in protostomes. To clarify the evolution of neurotrophin signaling components in bilateria, this work analyzes the genome of the crustacean Daphnia pulex as well as new genetic data from protostomes. Results The Daphnia genome encodes a neurotrophin, p75NTR and Trk orthologue together with Trkl, ROR, and NRK-RTKs. Drosophila Spz1, 2, 3, 5, 6 orthologues as well as two new groups of Spz proteins (Spz7 and 8 are also found in the Daphnia genome. Searching genbank and the genomes of Capitella, Helobdella and Lottia reveals neurotrophin signaling components in other protostomes. Conclusion It appears that a neurotrophin, Trk and p75NTR existed at the protostome/deuterostome split. In protostomes, a "neurotrophin superfamily" includes

  1. Polymorphisms of cytochrome P450 2B6 (CYP2B6) in cynomolgus and rhesus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Uehara, Shotaro; Yamazaki, Hiroshi

    2018-02-22

    Cytochrome P450 2B6 (CYP2B6) is an important drug-metabolizing enzyme and is expressed in liver. Although human CYP2B6 variants account for variable enzyme properties among individuals and populations, CYP2B6 genetic variants have not been investigated in cynomolgus macaques, widely used in drug metabolism studies. CYP2B6 was resequenced in 120 cynomolgus macaques and 23 rhesus macaques by direct sequencing. Twenty-three non-synonymous variants were found, of which 12 and 3 were unique to cynomolgus macaques and rhesus macaques, respectively. By functional characterization using the 14 variant proteins, 8 variants (V114I, R253C, M435I, V459M, L465P, C475S, R487C, and R487H) showed different rate (>1.5-fold) of testosterone 16β-hydroxylation to wild type. However, the four variants (M435I, L465P, C475S, and R487H) were analyzed in liver microsomes, and the catalytic rates were not substantially different from wild type. Macaque CYP2B6 was polymorphic, and the genotype could partly account for variable enzyme activities of macaque CYP2B6. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Cellular pH measurements in Emiliania huxleyi reveal pronounced membrane proton permeability.

    Science.gov (United States)

    Suffrian, K; Schulz, K G; Gutowska, M A; Riebesell, U; Bleich, M

    2011-05-01

    • To understand the influence of changing surface ocean pH and carbonate chemistry on the coccolithophore Emiliania huxleyi, it is necessary to characterize mechanisms involved in pH homeostasis and ion transport. • Here, we measured effects of changes in seawater carbonate chemistry on the fluorescence emission ratio of BCECF (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein) as a measure of intracellular pH (pH(i)). Out of equilibrium solutions were used to differentiate between membrane permeation pathways for H(+), CO(2) and HCO(3)(-). • Changes in fluorescence ratio were calibrated in single cells, resulting in a ratio change of 0.78 per pH(i) unit. pH(i) acutely followed the pH of seawater (pH(e)) in a linear fashion between pH(e) values of 6.5 and 9 with a slope of 0.44 per pH(e) unit. pH(i) was nearly insensitive to changes in seawater CO(2) at constant pH(e) and HCO(3)(-). An increase in extracellular HCO(3)(-) resulted in a slight intracellular acidification. In the presence of DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid), a broad-spectrum inhibitor of anion exchangers, E. huxleyi acidified irreversibly. DIDS slightly reduced the effect of pH(e) on pH(i). • The data for the first time show the occurrence of a proton permeation pathway in E. huxleyi plasma membrane. pH(i) homeostasis involves a DIDS-sensitive mechanism. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

  3. Structural organizations of yeast RNase P and RNase MRP holoenzymes as revealed by UV-crosslinking studies of RNA–protein interactions

    Science.gov (United States)

    Khanova, Elena; Esakova, Olga; Perederina, Anna; Berezin, Igor; Krasilnikov, Andrey S.

    2012-01-01

    Eukaryotic ribonuclease (RNase) P and RNase MRP are closely related ribonucleoprotein complexes involved in the metabolism of various RNA molecules including tRNA, rRNA, and some mRNAs. While evolutionarily related to bacterial RNase P, eukaryotic enzymes of the RNase P/MRP family are much more complex. Saccharomyces cerevisiae RNase P consists of a catalytic RNA component and nine essential proteins; yeast RNase MRP has an RNA component resembling that in RNase P and 10 essential proteins, most of which are shared with RNase P. The structural organizations of eukaryotic RNases P/MRP are not clear. Here we present the results of RNA–protein UV crosslinking studies performed on RNase P and RNase MRP holoenzymes isolated from yeast. The results indicate locations of specific protein-binding sites in the RNA components of RNase P and RNase MRP and shed light on the structural organizations of these large ribonucleoprotein complexes. PMID:22332141

  4. Effects of pH, temperature, and chemical structure on the stability of S-(purin-6-yl)-L-cysteine: evidence for a novel molecular rearrangement mechanism to yield N-(purin-6-yl)-L-cysteine.

    Science.gov (United States)

    Elfarra, A A; Hwang, I Y

    1996-01-01

    The stability of S-(purin-6-yl)-L-cysteine (SPC), a kidney-selective prodrug of 6-mercaptopurine and a putative metabolite of 6-chloropurine, was investigated under various pH and temperature conditions. At room temperature, the half-life (t 1/2) of SPC at either highly acidic (pH 3.6) or basic conditions (pH 9.6) was longer than at neutral or slightly acidic or basic conditions (pH 5.7-8.75). The primary degradation product, N-(purin-6-yl)-L-cysteine (NPC), was isolated using Sephadex LH-20 chromatography and characterized by 1H NMR and FAB/MS after derivatization with 2-iodoacetic acid. These results reveal novel stability requirements and implicate the cysteinyl amino group and the purinyl N-1 nitrogen in the mechanism of SPC rearrangement to NPC. Further evidence for this hypothesis was provided by the findings that the stability of SPC in phosphate buffer (pH 7.4) at 37 degrees C was similar to that of S-(guanin-6-yl)-L-cysteine, whereas S-(purin-6-yl)-N-acetyl-L-cysteine and S-(purin-6-yl)glutathione which have their cysteine amino groups blocked were much more stable than SPC. S-(Purin-6-yl)-L-homocysteine (SPHC) was also more stable than SPC, possibly because the formation of a 6-membered ring transition state as would be expected with SPHC is kinetically less favored than the formation of a 5-membered ring transition state as would be expected with SPC. These results may explain previous in vivo metabolism results of SPC and its analogs and may contribute to a better understanding of stability of structurally related cysteine S-conjugates.

  5. Customer Decision Making in Web Services with an Integrated P6 Model

    Science.gov (United States)

    Sun, Zhaohao; Sun, Junqing; Meredith, Grant

    Customer decision making (CDM) is an indispensable factor for web services. This article examines CDM in web services with a novel P6 model, which consists of the 6 Ps: privacy, perception, propensity, preference, personalization and promised experience. This model integrates the existing 6 P elements of marketing mix as the system environment of CDM in web services. The new integrated P6 model deals with the inner world of the customer and incorporates what the customer think during the DM process. The proposed approach will facilitate the research and development of web services and decision support systems.

  6. Fabrication of P3HT/gold nanoparticle LB films by P3HT templating Langmuir monolayer

    International Nuclear Information System (INIS)

    Chen, Liang-Huei; Hsu, Wen-Ping; Chan, Han-Wen; Lee, Yuh-Lang

    2014-01-01

    Highlights: • Addition of ODA into the P3HT monolayer can significantly improve the dispersion ability of P3HT molecules. • The adsorption ability of the P3HT monolayer to the dispersed AuNPs can also be enhanced by the presence of ODA. - Abstract: Regioregular poly(3-hexyl thiophene) (rr-P3HT) and mixed P3HT/octadecyl amine (ODA) were used as template monolayers to adsorb the gold nanoparticles (AuNPs) dispersed in subphase. The behaviors of P3HT and P3HT/ODA monolayers were investigated by surface pressure area per molecule (π–A) isotherms, transmission electron microscopy (TEM) and atomic force microscopy (AFM). The experimental results show that P3HT does not form a homogeneous film and tends to aggregate at the air/water interface. Meanwhile, the amount of AuNPs adsorbed by the P3HT monolayers is low, attributable to the weak interaction between AuNPs and P3HT. By introduction of ODA molecules into the P3HT monolayer, the spreading of P3HT molecules at the air/water interface is improved and the aggregation of P3HT is significantly inhibited. A nearly uniform and homogeneously mixed P3HT/ODA monolayer can be obtained when 50% of ODA is introduced. It is also found that the introduction of ODA can significantly increase the adsorption of AuNPs. For the mixed monolayer with low ratio of ODA (P3HT/ODA = 1/0.2), a higher concentration of adsorbed AuNPs was observed on the corresponding monolayer. However, when the ODA/P3HT ratio increases to 1/1, the AuNPs tend to form three-dimensional (3D) aggregates and the AuNPs cannot distribute well as a homogeneous monolayer. This result is ascribed to the increasing hydrophobicity of the adsorbed AuNPs because of capping of more ODA molecules

  7. Correlation between E-cadherin and p120 expression in invasive ductal breast cancer with a lobular component and MRI findings.

    Science.gov (United States)

    El Sharouni, Mary-Ann; Postma, Emily L; van Diest, Paul J

    2017-12-01

    Invasive breast cancer comprises a spectrum of histological changes with purely lobular cancer on one side and purely ductal cancer on the other, with many mixed lesions in between. In a previous study, we showed that in patients with any percentage lobular component at core needle biopsy, preoperative MRI leads to the detection of clinically relevant additional findings in a substantial percentage of patients, irrespective of the percentage of the lobular component. Detection of a small lobular component may however not be reproducible among pathologists. Loss of membrane expression of E-cadherin or p120 is useful biomarkers of ILC and may therefore support a more objective diagnosis. All patients diagnosed with breast cancer containing a lobular component of any percentage between January 2008 and October 2012 were prospectively offered preoperative MRI. Clinically relevant additional findings on MRI were verified by pathology evaluation. Expression patterns of E-cadherin and p120 were evaluated by immunohistochemistry on the core needle biopsy. MRI was performed in 109 patients. The percentage of lobular component was significantly increased in cases with aberrant E-cadherin or p120 expression (both p = lobular component in the core needle of their breast cancer.

  8. Proteomic characterization of plasmid pLA1 for biodegradation of polycyclic aromatic hydrocarbons in the marine bacterium, Novosphingobium pentaromativorans US6-1.

    Directory of Open Access Journals (Sweden)

    Sung Ho Yun

    Full Text Available Novosphingobium pentaromativorans US6-1 is a halophilic marine bacterium able to degrade polycyclic aromatic hydrocarbons (PAHs. Genome sequence analysis revealed that the large plasmid pLA1 present in N. pentaromativorans US6-1 consists of 199 ORFs and possess putative biodegradation genes that may be involved in PAH degradation. 1-DE/LC-MS/MS analysis of N. pentaromativorans US6-1 cultured in the presence of different PAHs and monocyclic aromatic hydrocarbons (MAHs identified approximately 1,000 and 1,400 proteins, respectively. Up-regulated biodegradation enzymes, including those belonging to pLA1, were quantitatively compared. Among the PAHs, phenanthrene induced the strongest up-regulation of extradiol cleavage pathway enzymes such as ring-hydroxylating dioxygenase, putative biphenyl-2,3-diol 1,2-dioxygenase, and catechol 2,3-dioxygenase in pLA1. These enzymes lead the initial step of the lower catabolic pathway of aromatic hydrocarbons through the extradiol cleavage pathway and participate in the attack of PAH ring cleavage, respectively. However, N. pentaromativorans US6-1 cultured with p-hydroxybenzoate induced activation of another extradiol cleavage pathway, the protocatechuate 4,5-dioxygenase pathway, that originated from chromosomal genes. These results suggest that N. pentaromativorans US6-1 utilizes two different extradiol pathways and plasmid pLA1 might play a key role in the biodegradation of PAH in N. pentaromativorans US6-1.

  9. Bacterial community dynamics and product distribution during pH-adjusted fermentation of vegetable wastes.

    Science.gov (United States)

    Ye, N-F; Lü, F; Shao, L-M; Godon, J-J; He, P-J

    2007-10-01

    To estimate the effect of pH on the structures of bacterial community during fermentation of vegetable wastes and to investigate the relationship between bacterial community dynamics and product distribution. The bacterial communities in five batch tests controlled at different pH values [uncontrolled (about pH 4), 5, 6, 7 and 8] were monitored by denaturing gradient gel electrophoresis (DGGE) and single-strand conformation polymorphism (SSCP). The two fingerprinting methods provided consistent results and principal component analysis indicated a close similarity of bacterial community at pH 7 and 8 in addition to those at pH 4-6. This clustering also corresponded to dominant metabolic pathway. Thus, pH 7-8 shifted from alcohol-forming to acid-forming, especially butyric acid, whereas both alcohol-forming and acid-forming dominated at pH 5-6, and at pH 4, fermentation was inhibited. Shannon-weaver index was calculated to analyse the DGGE profiles, which revealed that the bacterial diversities at pH 7 and 8 were the highest while those at pH 5 and 4 (uncontrolled) were the lowest. According to sequencing results of the bands excised from DGGE gels, lactic acid bacteria and Clostridium sp. were predominant at all pH values, but varieties in species were observed as pH changed and time prolonged. The bacterial community during fermentation was materially influenced by pH and the diverse product distribution was related to the shift of different bacterial population. The study reveals that the impact of pH on fermentation product distribution is implemented primarily by changes of bacterial community. It also provides information about the comparison of two fingerprinting methods, DGGE and SSCP.

  10. Dissociation kinetics of Fe(III)- and Al(III)-natural organic matter complexes at pH 6.0 and 8.0 and 25 °C

    Science.gov (United States)

    Jones, Adele M.; Pham, A. Ninh; Collins, Richard N.; Waite, T. David

    2009-05-01

    The rate at which iron- and aluminium-natural organic matter (NOM) complexes dissociate plays a critical role in the transport of these elements given the readiness with which they hydrolyse and precipitate. Despite this, there have only been a few reliable studies on the dissociation kinetics of these complexes suggesting half-times of some hours for the dissociation of Fe(III) and Al(III) from a strongly binding component of NOM. First-order dissociation rate constants are re-evaluated here at pH 6.0 and 8.0 and 25 °C using both cation exchange resin and competing ligand methods for Fe(III) and a cation exchange resin method only for Al(III) complexes. Both methods provide similar results at a particular pH with a two-ligand model accounting satisfactorily for the dissociation kinetics results obtained. For Fe(III), half-times on the order of 6-7 h were obtained for dissociation of the strong component and 4-5 min for dissociation of the weak component. For aluminium, the half-times were on the order of 1.5 h and 1-2 min for the strong and weak components, respectively. Overall, Fe(III) complexes with NOM are more stable than analogous complexes with Al(III), implying Fe(III) may be transported further from its source upon dilution and dispersion.

  11. Molybdenum (6) determination by the method of high-frequency and pH titration

    International Nuclear Information System (INIS)

    Lukianets, I.G.; Kulish, N.G.

    1981-01-01

    A possibility to determine Mo(6) using the method of high frequency and pH-metric titration is investigated. By means of the high frequency contact R-cell Mo(6) titration is performed using different precipitators: 8-oxiquinoline, lead nitrate and acetate and silver nitrate. It is established that the best conditions are achieved during titration of 67.2-1343 mg/10 ml Mo(6) with lead acetate (pH 4.5-6.5). Relative standard deviation Ssub(r) constitutes 0.005 pH-metric titration of Mo(6) with complexone 3 is studied. The range of Mo(6) concentrations determined constitutes 13.43-134.3 mg at pH initial value of 3.5-5.5. Relative standard deviation Ssub(r) constitutes 0.003. Techniques of molybdenum determination in ferromolybdenum using the method of high frequency and pH-metric titration are developed [ru

  12. Inhibition of p70S6K2 down-regulates Hedgehog/GLI pathway in non-small cell lung cancer cell lines

    Directory of Open Access Journals (Sweden)

    Kotani Hidehito

    2009-07-01

    Full Text Available Abstract Background The Hedgehog (HH pathway promotes tumorigenesis in a diversity of cancers. Activation of the HH signaling pathway is caused by overexpression of HH ligands or mutations in the components of the HH/GLI1 cascade, which lead to increased transactivation of GLI transcription factors. Although negative kinase regulators that antagonize the activity of GLI transcription factors have been reported, including GSK3β, PKA and CK1s, little is known regarding positive kinase regulators that are suitable for use on cancer therapeutic targets. The present study attempted to identify kinases whose silencing inhibits HH/GLI signalling in non-small cell lung cancer (NSCLC. Results To find positive kinase regulators in the HH pathway, kinome-wide siRNA screening was performed in a NSCLC cell line, A549, harboring the GLI regulatory reporter gene. This showed that p70S6K2-silencing remarkably reduced GLI reporter gene activity. The decrease in the activity of the HH pathway caused by p70S6K2-inhibition was accompanied by significant reduction in cell viability. We next investigated the mechanism for p70S6K2-mediated inhibition of GLI1 transcription by hypothesizing that GSK3β, a negative regulator of the HH pathway, is activated upon p70S6K2-silencing. We found that phosphorylated-GSK3β (Ser9 was reduced by p70S6K2-silencing, causing a decreased level of GLI1 protein. Finally, to further confirm the involvement of p70S6K2 in GLI1 signaling, down-regulation in GLI-mediated transcription by PI3KCA-inhibition was confirmed, establishing the pivotal role of the PI3K/p70S6K2 pathway in GLI1 cascade regulation. Conclusion We report herein that inhibition of p70S6K2, known as a downstream effector of the PI3K pathway, remarkably decreases GLI-mediated transactivation in NSCLC by reducing phosphorylated-GSK3β followed by GLI1 degradation. These results infer that p70S6K2 is a potential therapeutic target for NSCLC with hyperactivated HH/GLI pathway.

  13. Multiple isoforms of the human pentraxin serum amyloid P component

    DEFF Research Database (Denmark)

    Sørensen, Inge Juul; Andersen, Ove; Nielsen, EH

    1995-01-01

    major and several minor subpopulations of SAP. IEF of all SAP isolates showed a previously unreported degree of heterogeneity with six isoelectric forms (pKi range 5.5-6.1) and with minor interindividual differences in respect of isoelectric points. Total enzymatic deglycosylation of SAP reduced...

  14. Interfacial analysis and properties of regioregular Poly (3-Hexyl thiophene) spin-coated on an Indium tin oxide coated glass substrate

    CSIR Research Space (South Africa)

    Malgas, GF

    2008-08-01

    Full Text Available Interfacial analysis of the rrP3HT samples spincoated on a glass substrate was studied in detail using transmission electron microscopy (TEM) and SEM measurements. Very homogeneous and smooth polymer (P3HT and PEDOT:PSS) layers are observed...

  15. Extractability of plutonium-238 and curium-242 from a contaminated soil as a function of pH and certain soil components. CH3COOH-NH4OH system

    International Nuclear Information System (INIS)

    Nishita, H.

    1978-01-01

    Extractability of 238 Pu and 242 Cm from an artificially contaminated soil as a function of pH and certain soil components was examined with an equilibrium batch technique by the use of a CH 3 COOH--NH 4 OH extracting system. The influence of various soil components on 238 Pu and 242 Cm extractability was determined indirectly by selective removal of the components from the soil. The soil organic matter appeared to have a major influence on the extractability of these radionuclides. Though to a lesser extent, free iron oxides exerted an influence also. Before removal of soil organic matter, the extractability curves for these radionuclides were qualitatively similar in general form. The nature of this form is discussed. Within the contaminated, untreated soil, the 238 Pu and 242 Cm extractability ranged from 0.60 to 30.8% and 0.11 to 14.83% of dose, respectively, depending on the pH of the extracting solution. The liquid-to soild-phase ratio (K'/sub d/) values ranged from 3.5 x 10 -4 to 2.7 x 10 -2 for 238 Pu and 0.9 x 10 -4 to 1.4 x 10 -2 for 242 Cm. Very low extractability occurred in the pH range from approx. 8.6 to approx. 9.7 for 238 Pu and from 7.6 to approx. 9.7 for 242 Cm

  16. Peculiarities of component interaction in {l_brace}Gd, Er{r_brace}-V-Sn Ternary systems at 870 K and crystal structure of RV{sub 6}Sn{sub 6} stannides

    Energy Technology Data Exchange (ETDEWEB)

    Romaka, L., E-mail: romakal@franko.lviv.ua [Inorganic Chemistry Department, Ivan Franko Lviv National University, Kyryla and Mefodiya str. 6, 79005 Lviv (Ukraine); Stadnyk, Yu. [Inorganic Chemistry Department, Ivan Franko Lviv National University, Kyryla and Mefodiya str. 6, 79005 Lviv (Ukraine); Romaka, V.V. [Department of Materials Engineering and Applied Physics, Lviv Polytechnic National University, Ustyyanovycha Str. 5, 79013 Lviv (Ukraine); Demchenko, P.; Stadnyshyn, M.; Konyk, M. [Inorganic Chemistry Department, Ivan Franko Lviv National University, Kyryla and Mefodiya str. 6, 79005 Lviv (Ukraine)

    2011-09-08

    Highlights: > {l_brace}Gd, Er{r_brace}-V-Sn ternary systems at 870 K are characterized by formation of stannides with general compositions RV{sub 6}Sn{sub 6}. > Isostructural RV{sub 6}Sn{sub 6} compounds were also found with Y, Dy, Ho, Tm, and Lu. > The crystal structure of RV{sub 6}Sn{sub 6} compounds was determined by powder diffraction method. > Structural analysis showed that RV{sub 6}Sn{sub 6} compounds (R = Gd, Dy-Tm, Lu) are disordered; YV{sub 6}Sn{sub 6} is characterized by structure ordering. - Abstract: The phase equilibria in the Gd-V-Sn and Er-V-Sn ternary systems were studied at 870 K by means of X-ray and metallographic analyses in the whole concentration range. Both Gd-V-Sn and Er-V-Sn systems are characterized by formation of one ternary compound at investigated temperature, with stoichiometry RV{sub 6}Sn{sub 6} (SmMn{sub 6}Sn{sub 6}-type, space group P6/mmm, a = 0.55322(3) nm, c = 0.91949(7) nm for Gd, a = 0.55191(2) nm, c = 0.91869(8) nm for Er). Solubility of the third component in the binary compounds was not observed. Compounds with the SmMn{sub 6}Sn{sub 6}-type were also found with Dy, Ho, Tm, and Lu, while YV{sub 6}Sn{sub 6} compound crystallizes in HfFe{sub 6}Ge{sub 6} structure type. All investigated compounds are the first ternary stannides with rare earth elements and vanadium.

  17. Rigid-rod polyamides and polyimides derived from 4,3 ''-diamino-2 ',6 '-diphenyl- or di(4-biphenylyl)-p-terphenyl and 4-amino-4 ''-carboxy-2 ',6 '-diphenyl-p-terphenyl

    NARCIS (Netherlands)

    Spiliopoulos, IK; Mikroyannidis, JA; Tsivgoulis, GM

    1998-01-01

    4,3 "-Diamino-2',6'-diphenyl- or di(4-biphenylyl)p-terphenyl (3a or 3b) and 4-amino-4 "-carboxy-2',6'-diphenyl-p-terphenyl (6) were synthesized through pyrylium salts and used for the preparation of rigid-rod polyamides and polyimides. The polymers were characterized by inherent viscosity, elemental

  18. High-resolution two-photon spectroscopy of a 5 p56 p ←5 p6 transition of xenon

    Science.gov (United States)

    Altiere, Emily; Miller, Eric R.; Hayamizu, Tomohiro; Jones, David J.; Madison, Kirk W.; Momose, Takamasa

    2018-01-01

    We report high-resolution Doppler-free two-photon excitation spectroscopy of Xe from the ground state to the 5 p5(P 3 /2 2 ) 6 p [3 /2 ] 2 2 electronic excited state. This is a first step to developing a comagnetometer using polarized 129Xe atoms for planned neutron electric dipole moment measurements at TRIUMF. Narrow linewidth radiation at 252.5 nm produced by a continuous wave laser was built up in an optical cavity to excite the two-photon transition, and the near-infrared emission from the 5 p56 p excited state to the 5 p56 s intermediate electronic state was used to detect the two-photon transition. Hyperfine constants and isotope shift parameters were evaluated and compared with previously reported values. In addition, the detected photon count rate was estimated from the observed intensities.

  19. Development and protection challenges of the Syrian refugee crisis

    Directory of Open Access Journals (Sweden)

    Roger Zetter

    2014-09-01

    Full Text Available The Syria Regional Response Plan 6 (RRP6 2014 provides an increased focus on early recovery, social cohesion interventions and a transition from assistance to evelopment-led interventions, alongside the continuing large-scale humanitarian assistance and protection programme.

  20. Identification of Rotavirus VP6-Specific CD4+ T Cell Epitopes in a G1P[8] Human Rotavirus-Infected Rhesus Macaque

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    2008-01-01

    Full Text Available A non-human primate model was used to evaluate its potential for identification of rotavirus viral protein 6 (VP6 CD4+ T cell epitopes. Four juvenile rhesus macaques were inoculated with a mixed inoculum (G1P[8] and G9P[8] of human rotaviruses. Infection accompanied by G1P[8] shedding was achieved in the two macaques that had no rotavirus immunoglobulin A (IgA in plasma. To measure the interferon gamma (IFN-γ and tumor necrosis factor (TNF anti-viral cytokines produced by peripheral CD4+ cells that recognize VP6 epitopes, whole blood cells from one infected macaque were stimulated in vitro with VP6 peptides. Stimulation with peptide pools derived from the simian rotavirus VP6 161–395 region revealed reactivity of CD4+ T cells with the VP6 281–331 domain. A VP6 301–315 region was identified as the epitope responsible for IFN-γ production while a broader VP6 293–327 domain was linked to TNF production. These results suggest that human rotavirus-infected macaques can be used for identification of additional epitopes and domains to address specific questions related to the development of pediatric vaccines.

  1. Genetically encoded pH-indicators reveal activity-dependent cytosolic acidification of Drosophila motor nerve termini in vivo

    Science.gov (United States)

    Rossano, Adam J; Chouhan, Amit K; Macleod, Gregory T

    2013-01-01

    All biochemical processes, including those underlying synaptic function and plasticity, are pH sensitive. Cytosolic pH (pHcyto) shifts are known to accompany nerve activity in situ, but technological limitations have prevented characterization of such shifts in vivo. Genetically encoded pH-indicators (GEpHIs) allow for tissue-specific in vivo measurement of pH. We expressed three different GEpHIs in the cytosol of Drosophila larval motor neurons and observed substantial presynaptic acidification in nerve termini during nerve stimulation in situ. SuperEcliptic pHluorin was the most useful GEpHI for studying pHcyto shifts in this model system. We determined the resting pH of the nerve terminal cytosol to be 7.30 ± 0.02, and observed a decrease of 0.16 ± 0.01 pH units when the axon was stimulated at 40 Hz for 4 s. Realkalinization occurred upon cessation of stimulation with a time course of 20.54 ± 1.05 s (τ). The chemical pH-indicator 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein corroborated these changes in pHcyto. Bicarbonate-derived buffering did not contribute to buffering of acid loads from short (≤4 s) trains of action potentials but did buffer slow (∼60 s) acid loads. The magnitude of cytosolic acid transients correlated with cytosolic Ca2+ increase upon stimulation, and partial inhibition of the plasma membrane Ca2+-ATPase, a Ca2+/H+ exchanger, attenuated pHcyto shifts. Repeated stimulus trains mimicking motor patterns generated greater cytosolic acidification (∼0.30 pH units). Imaging through the cuticle of intact larvae revealed spontaneous pHcyto shifts in presynaptic termini in vivo, similar to those seen in situ during fictive locomotion, indicating that presynaptic pHcyto shifts cannot be dismissed as artifacts of ex vivo preparations. PMID:23401611

  2. Synthesis of Polythiophene–Fullerene Hybrid Additives as Potential Compatibilizers of BHJ Active Layers

    Directory of Open Access Journals (Sweden)

    Sofia Kakogianni

    2016-12-01

    Full Text Available Perfluorophenyl functionalities have been introduced as side chain substituents onto regioregular poly(3-hexyl thiophene (rr-P3HT, under various percentages. These functional groups were then converted to azides which were used to create polymeric hybrid materials with fullerene species, either C60 or C70. The P3HT–fullerene hybrids thus formed were thereafter evaluated as potential compatibilizers of BHJ active layers comprising P3HT and fullerene based acceptors. Therefore, a systematic investigation of the optical and morphological properties of the purified polymer–fullerene hybrid materials was performed, via different complementary techniques. Additionally, P3HT:PC70BM blends containing various percentages of the herein synthesized hybrid material comprising rr-P3HT and C70 were investigated via Transmission Electron Microscopy (TEM in an effort to understand the effect of the hybrids as additives on the morphology and nanophase separation of this typically used active layer blend for OPVs.

  3. P-I Snake Venom Metalloproteinase Is Able to Activate the Complement System by Direct Cleavage of Central Components of the Cascade

    Science.gov (United States)

    Pidde-Queiroz, Giselle; Magnoli, Fábio Carlos; Portaro, Fernanda C. V.; Serrano, Solange M. T.; Lopes, Aline Soriano; Paes Leme, Adriana Franco; van den Berg, Carmen W.; Tambourgi, Denise V.

    2013-01-01

    Background Snake Venom Metalloproteinases (SVMPs) are amongst the key enzymes that contribute to the high toxicity of snake venom. We have recently shown that snake venoms from the Bothrops genus activate the Complement system (C) by promoting direct cleavage of C-components and generating anaphylatoxins, thereby contributing to the pathology and spread of the venom. The aim of the present study was to isolate and characterize the C-activating protease from Bothrops pirajai venom. Results Using two gel-filtration chromatography steps, a metalloproteinase of 23 kDa that activates Complement was isolated from Bothrops pirajai venom. The mass spectrometric identification of this protein, named here as C-SVMP, revealed peptides that matched sequences from the P-I class of SVMPs. C-SVMP activated the alternative, classical and lectin C-pathways by cleaving the α-chain of C3, C4 and C5, thereby generating anaphylatoxins C3a, C4a and C5a. In vivo, C-SVMP induced consumption of murine complement components, most likely by activation of the pathways and/or by direct cleavage of C3, leading to a reduction of serum lytic activity. Conclusion We show here that a P-I metalloproteinase from Bothrops pirajai snake venom activated the Complement system by direct cleavage of the central C-components, i.e., C3, C4 and C5, thereby generating biologically active fragments, such as anaphylatoxins, and by cleaving the C1-Inhibitor, which may affect Complement activation control. These results suggest that direct complement activation by SVMPs may play a role in the progression of symptoms that follow envenomation. PMID:24205428

  4. WARM SPITZER OBSERVATIONS OF THREE HOT EXOPLANETS: XO-4b, HAT-P-6b, AND HAT-P-8b

    Energy Technology Data Exchange (ETDEWEB)

    Todorov, Kamen O. [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States); Deming, Drake [Planetary Systems Laboratory, NASA' s Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Knutson, Heather A. [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Burrows, Adam [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 05844 (United States); Sada, Pedro V. [Department of Physics and Mathematics, University of Monterrey, Monterrey (Mexico); Cowan, Nicolas B. [Department of Physics and Astronomy, Northwestern University, Evanston, IL 60208 (United States); Agol, Eric [Department of Astronomy, University of Washington, Box 351580, Seattle, WA 98195 (United States); Desert, Jean-Michel; Charbonneau, David [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Fortney, Jonathan J.; Laughlin, Gregory [Department of Astronomy and Astrophysics, University of California at Santa Cruz, Santa Cruz, CA 95064 (United States); Langton, Jonathan [Department of Physics, Principia College, Elsah, IL 62028 (United States); Showman, Adam P.; Lewis, Nikole K. [Lunar and Planetary Laboratory, University of Arizona, Tucson, AZ 85721 (United States)

    2012-02-10

    We analyze Warm Spitzer/Infrared Array Camera observations of the secondary eclipses of three planets, XO-4b, HAT-P-6b, and HAT-P-8b. We measure secondary eclipse amplitudes at 3.6 {mu}m and 4.5 {mu}m for each target. XO-4b exhibits a stronger eclipse depth at 4.5 {mu}m than at 3.6 {mu}m, which is consistent with the presence of a temperature inversion. HAT-P-8b shows a stronger eclipse amplitude at 3.6 {mu}m and is best described by models without a temperature inversion. The eclipse depths of HAT-P-6b can be fitted with models with a small or no temperature inversion. We consider our results in the context of a postulated relationship between stellar activity and temperature inversion and a relationship between irradiation level and planet dayside temperature, as discussed by Knutson et al. and Cowan and Agol, respectively. Our results are consistent with these hypotheses, but do not significantly strengthen them. To measure accurate secondary eclipse central phases, we require accurate ephemerides. We obtain primary transit observations and supplement them with publicly available observations to update the orbital ephemerides of the three planets. Based on the secondary eclipse timing, we set upper boundaries for ecos ({omega}) for HAT-P-6b, HAT-P-8b, and XO-4b and find that the values are consistent with circular orbits.

  5. 6-REXOS: Upper Limb Exoskeleton Robot with Improved pHRI

    Directory of Open Access Journals (Sweden)

    Malin Gunasekara

    2015-04-01

    Full Text Available Close interaction can be observed between an exoskeleton robot and its wearer. Therefore, appropriate physical human-robot interaction (pHRI should be considered when designing an exoskeleton robot to provide safe and comfortable motion assistance. Different features have been used in recent studies to enhance the pHRI in upper-limb exoskeleton robots. However, less attention has been given to integrating kinematic redundancy into upper-limb exoskeleton robots to improve the pHRI. In this context, this paper proposes a six-degrees-of-freedom (DoF upper-limb exoskeleton robot (6-REXOS for the motion assistance of physically weak individuals. The 6-REXOS uses a kinematically different structure to that of the human lower arm, where the exoskeleton robot is worn. The 6-REXOS has four active DoFs to generate the motion of the human lower arm. Furthermore, two flexible bellow couplings are attached to the wrist and elbow joints to generate two passive DoFs. These couplings not only allow translational motion in wrist and elbow joints but also a redundancy in the robot. Furthermore, the compliance of the flexible coupling contributes to avoiding misalignments between human and robot joint axes. The redundancy in the 6-REXOS is verified based on manipulability index, minimum singular value, condition number and manipulability ellipsoids. The 6-REXOS and a four-DoF exoskeleton robot are compared to verify the manipulation advantage due to the redundancy. The four-DoF exoskeleton robot is designed by excluding the two passive DoFs of the 6-REXOS. In addition, a kinematic model is proposed for the human lower arm to validate the performance of the 6-REXOS. Kinematic analysis and simulations are carried out to validate the 6-REXOS and human-lower-arm model.

  6. Risk factors for aggressive recurrent respiratory papillomatosis in adults and juveniles.

    Directory of Open Access Journals (Sweden)

    Turid Omland

    Full Text Available In this cohort study we examined whether gender, age at onset, observation time or human papillomavirus (HPV genotype are risk factors for an aggressive clinical course in Recurrent Respiratory Papillomatosis (RRP. Clinical data from patient records comprised gender, age at onset, date of first endolaryngeal procedure with biopsy, date of last follow-up, total number of endolaryngeal procedures, and complications during the observation period. Disease was defined as juvenile (JoRRP or adult onset (AoRRP according to whether the disease was acquired before or after the age of 18. Aggressive disease was defined as distal spread, tracheostomy, four surgical operations annually or >10 surgeries in total. DNA was extracted from formalin-fixed paraffin-embedded tissue. HPV genotyping was performed by quantitative PCR assay identifying 15 HPV genotypes. The study included 224 patients. The majority were males (141/174 in AoRRPs and 31/50 in JoRRPs; p = 0.005. The median follow-up from initial diagnosis was 12.0 years (IQR 3.7-32.9 for JoRRPs and 4.0 years (IQR 0.8-11.7 for AoRRPs. The disease was more aggressive in juveniles than adults (p10 years (OR = 13.41, 95% CI [5.46, 32.99[, p10 years were risk factors for an aggressive disease course in AoRRPs.

  7. Microglia P2Y6 receptor is related to Parkinson’s disease through neuroinflammatory process

    Directory of Open Access Journals (Sweden)

    Xiaodong Yang

    2017-02-01

    Full Text Available Abstract Background Microglia in the central nervous system (CNS were reported to play crucial role in neurodegeneration. Previous studies showed that P2Y6 receptor (P2Y6R mainly contributed to microglia activation and phagocytosis in CNS. However, the level of P2Y6R in Parkinson’s disease (PD patients is unclear. Therefore, we measured the level of P2Y6R in PD patients and speculated whether it could be a potential biomarker for PD. Given on the basis that P2Y6R was higher in PD patients, we further explored the mechanisms underlying P2Y6R in the pathogenesis of PD. Methods We tested the expression level of P2Y6R in the peripheral blood mononuclear cells (PBMCs among 145 PD patients, 170 healthy controls, and 30 multiple system atrophy (MSA patients. We also used a lipopolysaccharide (LPS-stimulated microglial cell culture model to investigate (i the effects of LPS on P2Y6R expression with western blot and RT-PCR, (ii the effects of LPS on UDP expression using HPLC, (iii the effects of UDP/P2Y6R signaling on cytokine expression using western blot, RT-PCR, and ELISA, and (iv the signaling pathways activated by the P2Y6R involved in the neuroinflammation. Results Expression levels of P2Y6R in PD patients were higher than healthy controls and MSA patients. P2Y6R could be a good biomarker of PD. P2Y6R was also upregulated in LPS-treated BV-2 cells and involved in proinflammatory cytokine release through an autocrine loop based on LPS-triggered UDP secretion and accelerated neuroinflammatory responses through the ERK1/2 pathway. Importantly, blocking UDP/P2Y6R signaling could reverse these pathological processes. Conclusions P2Y6R may be a potential clinical biomarker of PD. Blocking P2Y6R may be a potential therapeutic approach to the treatment of PD patients through inhibition of microglia-activated neuroinflammation.

  8. Two homologous Agr-like quorum-sensing systems cooperatively control adherence, cell morphology, and cell viability properties in Lactobacillus plantarum WCFS1

    NARCIS (Netherlands)

    Fujii, T.; Ingham, C.J.; Nakayama, J.; Beerthuyzen, M.M.; Kunuki, R.; Molenaar, D.; Sturme, M.H.J.; Vaughan, E.E.; Kleerebezem, M.; Vos, de W.M.

    2008-01-01

    A two-component regulatory system of Lactobacillus plantarum, encoded by genes designated lamK and lamR (hpk10 and rrp10), was studied. The lamK and lamR genes encode proteins which are highly homologous to the quorum-sensing histidine kinase LamC and the response regulator LamA, respectively.

  9. Health-related quality of life after radical retropubic prostatectomy and permanent prostate brachytherapy. A 3-year follow-up study

    International Nuclear Information System (INIS)

    Hashine, Katsuyoshi; Yuasa, Akihito; Shinomori, Kensuke; Ninomiya, Iku; Kataoka, Masaaki; Yamashita, Natsumi

    2011-01-01

    The objective of this study was to examine quality of life (QOL) for 3 years after radical retropubic prostatectomy (RRP) or permanent prostate brachytherapy (PPB) and to determine differences between the two procedures. In all 107 patients who underwent RRP and 91 who received PPB between October 2005 and July 2007 were included in this study. QOL surveys were performed using the international prostate symptom score (IPSS), the Medical Outcome Study 8-items short form health survey and the expanded prostate cancer index composite at baseline and 1, 3, 6, 12 and 36 months after treatment. At 3 years, all parameters for general QOL and almost all for disease-specific QOL were similar to those at 12 months. Urinary continence after RRP slightly improved from 12 months to 3 years, but it was still significantly worse than that after PPB. Scores for urinary irritation or obstruction and for bowel function and bother at 3 years were similar between the two groups. Sexual function and bother did not change between 12 months and 3 years in either group. Sexual function at 3 years after RRP was worse than that after PPB. Recovery from urinary incontinence and sexual function after RRP with nerve sparing were similar to those after PPB. Urinary incontinence at 3 years correlated with the treatment method and patients' age, whereas urinary irritation/obstruction and urinary bother correlated with the pre-treatment IPSS. QOL assessment represents an important issue in prostate cancer management. Our findings are likely to be of aid in the development of a treatment plan for prostate cancer patients. (author)

  10. Continence following radical retropubic prostatectomy using self-reporting instruments.

    Science.gov (United States)

    Lepor, Herbert; Kaci, Ledia; Xue, Xiaonan

    2004-03-01

    We performed a global self-assessment of continence following radical retropubic prostatectomy (RRP) and determined how this global self-assessment of continence correlates with commonly used definitions of continence. Between October 2000 and February 2002 all men who underwent RRP were encouraged to complete the University of California-Los Angeles Prostate Cancer Index 3, 6, 12 and 24 months postoperatively. Beginning October 2002 a single question capturing the patient global self-assessment of continence status was added to the postoperative continence assessment. The study design was cross-sectional since only continence surveys submitted between October 2002 through February 2003 were evaluated. Sensitivity, specificity and kappa coefficient was determined for the relationship between the patient global assessment of continence vs the definition of continence based on pad requirement, problem due to incontinence and frequency of incontinence. Continence progressively improved 3 to 24 months following RRP for all continence outcomes. At 24 months following RRP 97.1% of men considered themselves continent, while 97.1%, 94.1% and 97.1% were considered continent using continence definitions, including the requirement of no or 1 pad in a 24-hour interval, no or slight bother due to incontinence and total control or occasional dribbling, respectively. Our 3 definitions of continence derived from responses to the University of California-Los Angeles Prostate Cancer Index had excellent agreement with patient global self-assessment of continence (kappa coefficients between 0.76 and 0.83). The majority of men achieve continence without invasive intervention following RRP. Final continence status should be ascertained at 24 months. The patient global assessment of continence provides face validity for other definitions of continence based on responses to validated self-administered questionnaires.

  11. Spectrofluorimetric determination of benzoimidazolic pesticides: Effect of p-sulfonatocalix[6]arene and cyclodextrins

    International Nuclear Information System (INIS)

    Pacioni, Natalia L.; Sueldo Occello, Valeria N.; Lazzarotto, Marcio; Veglia, Alicia V.

    2008-01-01

    The effect of the addition of a macrocyclic host (H) such as p-sulfonatocalix[6]arene (C6S), native and modified cyclodextrins (CDs), on the fluorescence of benzoimidazolic fungicides (P), like Benomyl (BY) and Carbendazim (CZ), has been studied. The fluorescence of BY in water at pH 1.000 and 25.0 deg. C was increased in the presence of C6S, αCD and hydroxypropyl-β-CD (HPCD). The association constants determined by fluorescence enhancement showed weak interactions (K A ∼ 10 1 to 10 2 M -1 ) between the fungicide with both CDs, whereas they were stronger with C6S (K A ∼ 10 5 M -1 ). Molecular recognition of BY for C6S was mainly attributed to electrostatic interactions, and for CDs to the hydrophobic effect and hydrogen bond formation. On the other hand, the fluorescent behaviour of CZ in the presence of C6S at pH 6.994 was interpreted as the formation of two complexes with 1:1 (P:H) and 1:2 (P:H 2 ) stoichiometry, the latter being less fluorescent than the free analyte. Relative fluorescence quantum yield ratios between the complexed and free BY (φ P:H /φ P ) were 2.00 ± 0.05, 1.40 ± 0.03 and 2.8 ± 0.4 for C6S, αCD and HPCD, respectively. The analytical parameters improved in the presence of C6S and CDs. The best limit of detection (L D , ng mL -1 ) was 17.4 ± 0.8 with HPCD. The proposed method with C6S and HPCD was successfully applied to fortified samples of tap water and orange flesh extract with good recoveries (91-106%) and R.S.D. (≤2%) by triplicate analysis. The method is rapid, direct and simple and needs no previous degradation or derivatization reaction

  12. Spectrofluorimetric determination of benzoimidazolic pesticides: Effect of p-sulfonatocalix[6]arene and cyclodextrins

    Energy Technology Data Exchange (ETDEWEB)

    Pacioni, Natalia L.; Sueldo Occello, Valeria N. [Instituto de Investigaciones en Fisico Quimica de Cordoba (INFIQC), Departamento de Quimica Organica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Ciudad Universitaria, 5000 Cordoba (Argentina); Lazzarotto, Marcio [Departamento de Quimica Organica, Instituto de Quimica, Universidade Federal do Rio Grande do Sul-UFRGS, 15003 Porto Alegre, R.S. (Brazil); Veglia, Alicia V. [Instituto de Investigaciones en Fisico Quimica de Cordoba (INFIQC), Departamento de Quimica Organica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Ciudad Universitaria, 5000 Cordoba (Argentina)], E-mail: aveglia@fcq.unc.edu.ar

    2008-08-22

    The effect of the addition of a macrocyclic host (H) such as p-sulfonatocalix[6]arene (C6S), native and modified cyclodextrins (CDs), on the fluorescence of benzoimidazolic fungicides (P), like Benomyl (BY) and Carbendazim (CZ), has been studied. The fluorescence of BY in water at pH 1.000 and 25.0 deg. C was increased in the presence of C6S, {alpha}CD and hydroxypropyl-{beta}-CD (HPCD). The association constants determined by fluorescence enhancement showed weak interactions (K{sub A} {approx} 10{sup 1} to 10{sup 2} M{sup -1}) between the fungicide with both CDs, whereas they were stronger with C6S (K{sub A} {approx} 10{sup 5} M{sup -1}). Molecular recognition of BY for C6S was mainly attributed to electrostatic interactions, and for CDs to the hydrophobic effect and hydrogen bond formation. On the other hand, the fluorescent behaviour of CZ in the presence of C6S at pH 6.994 was interpreted as the formation of two complexes with 1:1 (P:H) and 1:2 (P:H{sub 2}) stoichiometry, the latter being less fluorescent than the free analyte. Relative fluorescence quantum yield ratios between the complexed and free BY ({phi}{sup P:H}/{phi}{sup P}) were 2.00 {+-} 0.05, 1.40 {+-} 0.03 and 2.8 {+-} 0.4 for C6S, {alpha}CD and HPCD, respectively. The analytical parameters improved in the presence of C6S and CDs. The best limit of detection (L{sub D}, ng mL{sup -1}) was 17.4 {+-} 0.8 with HPCD. The proposed method with C6S and HPCD was successfully applied to fortified samples of tap water and orange flesh extract with good recoveries (91-106%) and R.S.D. ({<=}2%) by triplicate analysis. The method is rapid, direct and simple and needs no previous degradation or derivatization reaction.

  13. Identification of an evolutionary conserved SURF-6 domain in a family of nucleolar proteins extending from human to yeast

    International Nuclear Information System (INIS)

    Polzikov, Mikhail; Zatsepina, Olga; Magoulas, Charalambos

    2005-01-01

    The mammalian SURF-6 protein is localized in the nucleolus, yet its function remains elusive in the recently characterized nucleolar proteome. We discovered by searching the Protein families database that a unique evolutionary conserved SURF-6 domain is present in the carboxy-terminal of a novel family of eukaryotic proteins extending from human to yeast. By using the enhanced green fluorescent protein as a fusion protein marker in mammalian cells, we show that proteins from distantly related taxonomic groups containing the SURF-6 domain are localized in the nucleolus. Deletion sequence analysis shows that multiple regions of the SURF-6 protein are capable of nucleolar targeting independently of the evolutionary conserved domain. We identified that the Saccharomyces cerevisiae member of the SURF-6 family, named rrp14 or ykl082c, has been categorized in yeast databases to interact with proteins involved in ribosomal biogenesis and cell polarity. These results classify SURF-6 as a new family of nucleolar proteins in the eukaryotic kingdom and point out that SURF-6 has a distinct domain within the known nucleolar proteome that may mediate complex protein-protein interactions for analogous processes between yeast and mammalian cells

  14. Outline of material accountancy system for Rokkasho reprocessing plant

    International Nuclear Information System (INIS)

    Kitamura, Touko; Yamazaki Yoshihiro; Ai, Hironobu

    2004-01-01

    In January 2004, Facility Attachment (FA) for Rokkasho Reprocessing Plant (RRP) was entered into force and the safeguards has been implemented in accordance with the FA. So operator must carry out the effectual material accountancy on the basis of facility operation. RRP is large and complex facility and operated based on automatic and remote system. For efficient material accounting viewpoint, the system especially automatic data collection is established using RRP computer network. The paper describes the outline of material accountancy system, the structure of RRP computer network including how to collect the source data, to convert the batch data and the reporting. (author)

  15. Corrosion of carbon steel in the [P_1_4_6_6_6][Br] ionic liquid: The effects of γ-radiation and cover gas

    International Nuclear Information System (INIS)

    Morco, Ryan P.; Musa, Ahmed Y.; Momeni, Mojtaba; Wren, J.C.

    2016-01-01

    Highlights: • Carbon steel corrosion in non-aqueous ionic liquid ([P_1_4_6_6_6] [Br]) electrolyte. • Gamma-irradiation results to less corrosion, forming protective oxides. • Substantial corrosion is seen in the absence of gamma-radiation. • A corrosion mechanism is proposed for the observed results. - Abstract: The corrosion of carbon steel in the ionic liquid (IL) [P_1_4_6_6_6] [Br] was studied with the IL in contact with an inert (Ar) or oxidizing (air) cover gas in the presence and absence of γ-radiation. Significant corrosion was observed for the tests performed in the absence of γ-radiation while a protective oxide layer is formed in the presence of γ-radiation. The corrosion is attributed to the presence of impurity H_2O and O_2 dissolved in the IL, and a corrosion mechanism is proposed.

  16. pH dependent green synthesis of gold nanoparticles by completely C6-carboxylated curdlan under high temperature and various pH conditions.

    Science.gov (United States)

    Qiu, Wen-Yi; Wang, Kai; Wang, Yao-Yao; Ding, Zhi-Chao; Wu, Li-Xia; Cai, Wu-Dan; Yan, Jing-Kun

    2018-01-01

    A C6-carboxylated curdlan (C6-Cc) obtained from 4-acetamido-TEMPO-mediated oxidation of curdlan was used both as a reducing and stabilizing agent for green synthesis of pH-responsive AuNPs, which was carried out by controlling the pH of the C6-Cc solution at a high temperature (100°C). C6-Cc presented a semi-flexible random coil chain in the aqueous medium at pH 5.5 and became more expanded and rigid in alkaline conditions (pH 7.1-12.0), though the primary chemical structure of C6-Cc was virtually unchanged with the pH variation. The AuNPs prepared with C6-Cc at various pHs were characterized by various instrumental measurements. The shapes and sizes of AuNPs were found to be strongly dependent on the pH of the C6-Cc solution. The C6-Cc-decorated AuNPs exhibited a more well-dispersed spherical morphology with smaller particle sizes under alkaline conditions (pH 7.1-12.0). Through this study, a facile, simple, and green method has been demonstrated for preparation of stimuli-sensitive AuNPs using biocompatible polyanionic polysaccharides. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Evaluation and development plan of NRTA measurement methods for the Rokkasho Reprocessing Plant

    International Nuclear Information System (INIS)

    Li, T.K.; Hakkila, E.A.; Flosterbuer, S.F.

    1995-01-01

    Near-real-time accounting (NRTA) has been proposed as a safeguards method at the Rokkasho Reprocessing Plant (RRP), a large-scale commercial boiling water and pressurized water reactors spent-fuel reprocessing facility. NRTA for RRP requires material balance closures every month. To develop a more effective and practical NRTA system for RRP, we have evaluated NRTA measurement techniques and systems that might be implemented in both the main process and the co-denitration process areas at RRP to analyze the concentrations of plutonium in solutions and mixed oxide powder. Based on the comparative evaluation, including performance, reliability, design criteria, operation methods, maintenance requirements, and estimated costs for each possible measurement method, recommendations for development were formulated. This paper discusses the evaluations and reports on the recommendation of the NRTA development plan for potential implementation at RRP

  18. The potential health and economic benefits of preventing recurrent respiratory papillomatosis through quadrivalent human papillomavirus vaccination.

    Science.gov (United States)

    Chesson, Harrell W; Forhan, Sara E; Gottlieb, Sami L; Markowitz, Lauri E

    2008-08-18

    We estimated the health and economic benefits of preventing recurrent respiratory papillomatosis (RRP) through quadrivalent human papillomavirus (HPV) vaccination. We applied a simple mathematical model to estimate the averted costs and quality-adjusted life years (QALYs) saved by preventing RRP in children whose mothers had been vaccinated at age 12 years. Under base case assumptions, the prevention of RRP would avert an estimated USD 31 (range: USD 2-178) in medical costs (2006 US dollars) and save 0.00016 QALYs (range: 0.00001-0.00152) per 12-year-old girl vaccinated. Including the benefits of RRP reduced the estimated cost per QALY gained by HPV vaccination by roughly 14-21% in the base case and by 100% in the sensitivity analyses. More precise estimates of the incidence of RRP are needed, however, to quantify this impact more reliably.

  19. The Impact of Polymorphic Variations in the 5p15, 6p12, 6p21 and 15q25 Loci on the Risk and Prognosis of Portuguese Patients with Non-Small Cell Lung Cancer

    Science.gov (United States)

    de Mello, Ramon Andrade; Ferreira, Mónica; Soares-Pires, Filipa; Costa, Sandra; Cunha, João; Oliveira, Pedro; Hespanhol, Venceslau; Reis, Rui Manuel

    2013-01-01

    Introduction Polymorphic variants in the 5p15, 6p12, 6p21, and 15q25 loci were demonstrated to potentially contribute to lung cancer carcinogenesis. Therefore, this study was performed to assess the role of those variants in non-small cell lung cancer (NSCLC) risk and prognosis in a Portuguese population. Materials and Methods Blood from patients with NSCLC was prospectively collected. To perform an association study, DNA from these patients and healthy controls were genotyped for a panel of 19 SNPs using a Sequenom® MassARRAY platform. Kaplan-Meier curves were used to assess the overall survival (OS) and progression-free survival (PFS). Results One hundred and forty-four patients with NSCLC were successfully consecutively genotyped for the 19 SNPs. One SNP was associated with NSCLC risk: rs9295740 G/A. Two SNPs were associated with non-squamous histology: rs3024994 (VEGF intron 2) T/C and rs401681 C/T. Three SNPs were associated with response rate: rs3025035 (VEGF intron 7) C/T, rs833061 (VEGF –460) C/T and rs9295740 G/A. One SNP demonstrated an influence on PFS: rs401681 C/T at 5p15, p = 0.021. Four SNPs demonstrated an influence on OS: rs2010963 (VEGF +405 G/C), p = 0.042; rs3025010 (VEGF intron 5 C/T), p = 0.047; rs401681 C/T at 5p15, p = 0.046; and rs31489 C/A at 5p15, p = 0.029. Conclusions Our study suggests that SNPs in the 6p12, 6p21, and 5p15 loci may serve as risk, predictive and prognostic NSCLC biomarkers. In the future, SNPs identified in the genomes of patients may improve NSCLC screening strategies and therapeutic management as well. PMID:24039754

  20. Síntesis del 3-p-metoxibenzoil-4-hidroxi-6-p-metoxifenil-2H-piran-2-ona

    Directory of Open Access Journals (Sweden)

    María Soledad Ortiz

    2013-05-01

    Full Text Available During the study of conditions to prepare p-methoxybenzoylacetic acid methyl ester fromp-methoxyacetophenone andmethyl carbonate using sodium hydride in refluxing ethyl ether, the desired product was obtained with 82% yield. Moreover, a slight variation in reaction conditions, such as solvent and temperature, the 3-p-methoxy benzoyl-4-hydroxi-6-p-methoxyphenyl-2H-pyran-2-one was obtained as an unexpected major product.

  1. Functional analysis of CYP6ER1, a P450 gene associated with imidacloprid resistance in Nilaparvata lugens.

    Science.gov (United States)

    Pang, Rui; Chen, Meng; Liang, Zhikun; Yue, Xiangzhao; Ge, Hu; Zhang, Wenqing

    2016-10-10

    The cytochrome P450 CYP6ER1 has been reported to play an important role in imidacloprid resistance of the brown planthopper (BPH), Nilaparvata lugens, and is overexpressed in most resistant populations. In the present study, we confirmed that CYP6ER1 expression can be induced by certain levels of imidacloprid. Developmental expression analysis revealed that CYP6ER1 was expressed highly in the adult stage, and tissue distribution analysis showed that CYP6ER1 was expressed mainly in the fat body and midgut. RNA interference (RNAi) of CYP6ER1 and transgenic expression of CYP6ER1 in Drosophila melanogaster both suggested that the expression of CYP6ER1 is sufficient to confer imidacloprid resistance. Furthermore, we analyzed the interaction of imidacloprid and CYP6ER1 monooxygenase by using dynamic simulations and molecular docking. We found that Nitrogen atoms in the heterocycle of the imidacloprid molecule may bind to iron atoms in the center of the homology model of CYP6ER1 via 4,5-dihedro-1H-imidazole. This finding contributes to a better understanding of how CYP6ER1 takes part in the insecticide metabolism.

  2. One-dimensional zinc selenophosphates: A_2ZnP_2Se_6 (A = K, Rb, Cs)

    International Nuclear Information System (INIS)

    Haynes, Alyssa S.; Lee, Katherine; Kanatzidis, Mercouri G.

    2016-01-01

    The new compounds A_2ZnP_2Se_6 (A = K, Rb, Cs) were synthesized via molten salt flux syntheses. The crystals feature one-dimensional "1/_∞[ZnP_2Se_6]"2"- chains charge balanced by alkali metal ions between the chains. K_2ZnP_2Se_6 crystallizes in the monoclinic space group P2_1/c; cell parameters a = 12.537(3) Aa, b = 7.2742(14) Aa, c = 14.164(3) Aa, β = 109.63(3) , Z = 4, and V = 1216.7(4) Aa"3. Rb_2ZnP_2Se_6 and Cs_2ZnP_2Se_6 are isotypic, crystallizing in the triclinic space group P anti 1. Rb_2ZnP_2Se_6 has cell parameters of a = 7.4944(15) Aa, b = 7.6013(15) Aa, c = 12.729(3) Aa, α = 96.57(3) , β = 105.52(3) , γ = 110.54(3) , Z = 2, and V = 636.6(2) Aa"3. Cs_2ZnP_2Se_6 has cell parameters of a = 7.6543(6) Aa, b = 7.7006(6) Aa, c = 12.7373(11) Aa, α = 97.007(7) , β = 104.335(7) , γ = 109.241(6) , Z = 2, and V = 669.54(10) Aa"3. (Copyright copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  3. RNA-processing proteins regulate Mec1/ATR activation by promoting generation of RPA-coated ssDNA.

    Science.gov (United States)

    Manfrini, Nicola; Trovesi, Camilla; Wery, Maxime; Martina, Marina; Cesena, Daniele; Descrimes, Marc; Morillon, Antonin; d'Adda di Fagagna, Fabrizio; Longhese, Maria Pia

    2015-02-01

    Eukaryotic cells respond to DNA double-strand breaks (DSBs) by activating a checkpoint that depends on the protein kinases Tel1/ATM and Mec1/ATR. Mec1/ATR is activated by RPA-coated single-stranded DNA (ssDNA), which arises upon nucleolytic degradation (resection) of the DSB. Emerging evidences indicate that RNA-processing factors play critical, yet poorly understood, roles in genomic stability. Here, we provide evidence that the Saccharomyces cerevisiae RNA decay factors Xrn1, Rrp6 and Trf4 regulate Mec1/ATR activation by promoting generation of RPA-coated ssDNA. The lack of Xrn1 inhibits ssDNA generation at the DSB by preventing the loading of the MRX complex. By contrast, DSB resection is not affected in the absence of Rrp6 or Trf4, but their lack impairs the recruitment of RPA, and therefore of Mec1, to the DSB. Rrp6 and Trf4 inactivation affects neither Rad51/Rad52 association nor DSB repair by homologous recombination (HR), suggesting that full Mec1 activation requires higher amount of RPA-coated ssDNA than HR-mediated repair. Noteworthy, deep transcriptome analyses do not identify common misregulated gene expression that could explain the observed phenotypes. Our results provide a novel link between RNA processing and genome stability. © 2014 The Authors.

  4. Trehalose 6-phosphate phosphatases of Pseudomonas aeruginosa.

    Science.gov (United States)

    Cross, Megan; Biberacher, Sonja; Park, Suk-Youl; Rajan, Siji; Korhonen, Pasi; Gasser, Robin B; Kim, Jeong-Sun; Coster, Mark J; Hofmann, Andreas

    2018-04-24

    The opportunistic bacterium Pseudomonas aeruginosa has been recognized as an important pathogen of clinical relevance and is a leading cause of hospital-acquired infections. The presence of a glycolytic enzyme in Pseudomonas, which is known to be inhibited by trehalose 6-phosphate (T6P) in other organisms, suggests that these bacteria may be vulnerable to the detrimental effects of intracellular T6P accumulation. In the present study, we explored the structural and functional properties of trehalose 6-phosphate phosphatase (TPP) in P. aeruginosa in support of future target-based drug discovery. A survey of genomes revealed the existence of 2 TPP genes with either chromosomal or extrachromosomal location. Both TPPs were produced as recombinant proteins, and characterization of their enzymatic properties confirmed specific, magnesium-dependent catalytic hydrolysis of T6P. The 3-dimensional crystal structure of the chromosomal TPP revealed a protein dimer arising through β-sheet expansion of the individual monomers, which possess the overall fold of halo-acid dehydrogenases.-Cross, M., Biberacher, S., Park, S.-Y., Rajan, S., Korhonen, P., Gasser, R. B., Kim, J.-S., Coster, M. J., Hofmann, A. Trehalose 6-phosphate phosphatases of Pseudomonas aeruginosa.

  5. Design, Manufacture, and Experimental Serviceability Validation of ITER Blanket Components

    Science.gov (United States)

    Leshukov, A. Yu.; Strebkov, Yu. S.; Sviridenko, M. N.; Safronov, V. M.; Putrik, A. B.

    2017-12-01

    In 2014, the Russian Federation and the ITER International Organization signed two Procurement Arrangements (PAs) for ITER blanket components: 1.6.P1ARF.01 "Blanket First Wall" of February 14, 2014, and 1.6.P3.RF.01 "Blanket Module Connections" of December 19, 2014. The first PA stipulates development, manufacture, testing, and delivery to the ITER site of 179 Enhanced Heat Flux (EHF) First Wall (FW) Panels intended for withstanding the heat flux from the plasma up to 4.7MW/m2. Two Russian institutions, NIIEFA (Efremov Institute) and NIKIET, are responsible for the implementation of this PA. NIIEFA manufactures plasma-facing components (PFCs) of the EHF FW panels and performs the final assembly and testing of the panels, and NIKIET manufactures FW beam structures, load-bearing structures of PFCs, and all elements of the panel attachment system. As for the second PA, NIKIET is the sole official supplier of flexible blanket supports, electrical insulation key pads (EIKPs), and blanket module/vacuum vessel electrical connectors. Joint activities of NIKIET and NIIEFA for implementing PA 1.6.P1ARF.01 are briefly described, and information on implementation of PA 1.6.P3.RF.01 is given. Results of the engineering design and research efforts in the scope of the above PAs in 2015-2016 are reported, and results of developing the technology for manufacturing ITER blanket components are presented.

  6. Quantitative trait loci identified for blood chemistry components of an advanced intercross line of chickens under heat stress.

    Science.gov (United States)

    Van Goor, Angelica; Ashwell, Christopher M; Persia, Michael E; Rothschild, Max F; Schmidt, Carl J; Lamont, Susan J

    2016-04-14

    Heat stress in poultry results in considerable economic losses and is a concern for both animal health and welfare. Physiological changes occur during periods of heat stress, including changes in blood chemistry components. A highly advanced intercross line, created from a broiler (heat susceptible) by Fayoumi (heat resistant) cross, was exposed to daily heat cycles for seven days starting at 22 days of age. Blood components measured pre-heat treatment and on the seventh day of heat treatment included pH, pCO2, pO2, base excess, HCO3, TCO2, K, Na, ionized Ca, hematocrit, hemoglobin, sO2, and glucose. A genome-wide association study (GWAS) for these traits and their calculated changes was conducted to identify quantitative trait loci (QTL) using a 600 K SNP panel. There were significant increases in pH, base excess, HCO3, TCO2, ionized Ca, hematocrit, hemoglobin, and sO2, and significant decreases in pCO2 and glucose after 7 days of heat treatment. Heritabilities ranged from 0.01-0.21 for pre-heat measurements, 0.01-0.23 for measurements taken during heat, and 0.00-0.10 for the calculated change due to heat treatment. All blood components were highly correlated within measurement days, but not correlated between measurement days. The GWAS revealed 61 QTL for all traits, located on GGA (Gallus gallus chromosome) 1, 3, 6, 9, 10, 12-14, 17, 18, 21-28, and Z. A functional analysis of the genes in these QTL regions identified the Angiopoietin pathway as significant. The QTL that co-localized for three or more traits were on GGA10, 22, 26, 28, and Z and revealed candidate genes for birds' response to heat stress. The results of this study contribute to our knowledge of levels and heritabilities of several blood components of chickens under thermoneutral and heat stress conditions. Most components responded to heat treatment. Mapped QTL may serve as markers for genomic selection to enhance heat tolerance in poultry. The Angiopoietin pathway is likely involved in the

  7. Glucose 6P binds and activates HlyIIR to repress Bacillus cereus haemolysin hlyII gene expression.

    Directory of Open Access Journals (Sweden)

    Elisabeth Guillemet

    Full Text Available Bacillus cereus is a Gram-positive spore-forming bacterium causing food poisoning and serious opportunistic infections. These infections are characterized by bacterial accumulation despite the recruitment of phagocytic cells. We have previously shown that B. cereus Haemolysin II (HlyII induces macrophage cell death by apoptosis. In this work, we investigated the regulation of the hlyII gene. We show that HlyIIR, the negative regulator of hlyII expression in B. cereus, is especially active during the early bacterial growth phase. We demonstrate that glucose 6P directly binds to HlyIIR and enhances its activity at a post-transcriptional level. Glucose 6P activates HlyIIR, increasing its capacity to bind to its DNA-box located upstream of the hlyII gene, inhibiting its expression. Thus, hlyII expression is modulated by the availability of glucose. As HlyII induces haemocyte and macrophage death, two cell types that play a role in the sequestration of nutrients upon infection, HlyII may induce host cell death to allow the bacteria to gain access to carbon sources that are essential components for bacterial growth.

  8. Spatially dependent properties in a laser additive manufactured Ti–6Al–4V component

    Energy Technology Data Exchange (ETDEWEB)

    Palanivel, S.; Dutt, A.K. [Center for Friction Stir Processing, Department of Materials Science and Engineering, University of North Texas, Denton, TX 76203 (United States); Faierson, E.J. [Quad City Manufacturing Laboratory, Western Illinois University, Rock Island, IL 61201 (United States); Mishra, R.S., E-mail: Rajiv.Mishra@unt.edu [Center for Friction Stir Processing, Department of Materials Science and Engineering, University of North Texas, Denton, TX 76203 (United States)

    2016-01-27

    Automotive and aerospace sectors have provided a strong product pull for advancing powder bed fusion technologies. However, as these technologies mature towards large-scale production, issues of build consistency and surface finish are of concern. In order to study these issues, a Ti–6Al–4V mini impeller was fabricated using laser additive manufacturing. The primary objective of this work was to quantify and correlate the variation in mechanical properties and microstructure across and along different locations in the component. Hardness measured at various build locations revealed a stronger hub (highest value: 428 HV) with lower spatial variations in comparison to the blade (highest value: 415 HV). Additional examinations to assess anisotropy showed an average hardness of 397±11 and 385±8 HV along the blade build (Z) and longitudinal (X) directions respectively. Region and direction specific uniaxial tensile testing of the samples indicated a strong hub bottom with yield strength (YS) of 1193 MPa, ultimate tensile strength (UTS) of 1310 MPa, and a total elongation of 5.5% in the longitudinal direction. Although the low elongation value correlates well with previous studies, strength is significantly higher and is attributed to having a complete martensitic structure induced by the high cooling rates experienced at the build–substrate interface. On the other hand, YS, UTS and total elongation in the blade were recorded as 978 MPa, 1096 MPa and 9.12%, respectively, along the build direction. Microstructure in the blade region consisted of α′ and α+β. When compared to the polished specimen in the blade, its unpolished counterpart yielded at 896 MPa, had UTS of 1018 MPa, and elongation of 6.24%. An understanding of the reduction in performance of the unfinished blade would help in deciding the need for surface finishing operations after fabrication.

  9. Spatially dependent properties in a laser additive manufactured Ti–6Al–4V component

    International Nuclear Information System (INIS)

    Palanivel, S.; Dutt, A.K.; Faierson, E.J.; Mishra, R.S.

    2016-01-01

    Automotive and aerospace sectors have provided a strong product pull for advancing powder bed fusion technologies. However, as these technologies mature towards large-scale production, issues of build consistency and surface finish are of concern. In order to study these issues, a Ti–6Al–4V mini impeller was fabricated using laser additive manufacturing. The primary objective of this work was to quantify and correlate the variation in mechanical properties and microstructure across and along different locations in the component. Hardness measured at various build locations revealed a stronger hub (highest value: 428 HV) with lower spatial variations in comparison to the blade (highest value: 415 HV). Additional examinations to assess anisotropy showed an average hardness of 397±11 and 385±8 HV along the blade build (Z) and longitudinal (X) directions respectively. Region and direction specific uniaxial tensile testing of the samples indicated a strong hub bottom with yield strength (YS) of 1193 MPa, ultimate tensile strength (UTS) of 1310 MPa, and a total elongation of 5.5% in the longitudinal direction. Although the low elongation value correlates well with previous studies, strength is significantly higher and is attributed to having a complete martensitic structure induced by the high cooling rates experienced at the build–substrate interface. On the other hand, YS, UTS and total elongation in the blade were recorded as 978 MPa, 1096 MPa and 9.12%, respectively, along the build direction. Microstructure in the blade region consisted of α′ and α+β. When compared to the polished specimen in the blade, its unpolished counterpart yielded at 896 MPa, had UTS of 1018 MPa, and elongation of 6.24%. An understanding of the reduction in performance of the unfinished blade would help in deciding the need for surface finishing operations after fabrication.

  10. Synthesis and reactions of 4-(p-methoxybenzyl-6-[5,6,7,8-tetrahydro-2-naphthyl]-pyridazin-3(2H-one

    Directory of Open Access Journals (Sweden)

    NAGWA M.S. EL-DIN HARB

    1999-11-01

    Full Text Available The condensation of 4-(p-methoxybenzyl-6-[5,6,7,8-tetrahydro-2-naphthyl]-pyridazin-3(2H-one (3, prepared by the reaction of 6-[5,6,7,8-tetrahydro-2-naphthyl]-4,5-dihydropyridazin-3(2H-one (1 and anisaldehyde, with dimethyl sulphate, formaldehyde and acrylonitrile, and also the formation of the Mannich base, proceeded smoothly at the 2-position to give compounds 4,5,6,7, respectively. 4-p-Methoxybenzyl-3-chloro-6-[5,6,7,8-tetrahydro-2-naphthyl]-pyridazine (9 was prepared in law yield by the action of phosphorus oxychloride on 3. The reaction of 9 with benzylamine, aniline and piperidine gave 10a,b,c, respectively. 4-p-Methoxybenzyl-6-[5,6,7,8-tetrahydro-2-napthyl]pyridazine-3(2H-thione (12 was prepared either by the action of thiourea on 9, or by the reaction of 3 with phosphorus pentasulphide. The reaction of these thiones with acrylonitrile, morpholine and piperidine to give 13 and 14 a,b, respectively, were also investigated.

  11. Parity nonconserving asymmetry in p-p scattering up to 6 GeV/c

    International Nuclear Information System (INIS)

    Oka, Takamitsu.

    1981-03-01

    A parity nonconserving asymmetry in proton-proton scattering is studied. We calculate the longitudinal analyzing power for the momentum of incident proton up to P sub(L) -- 6 GeV/c. For the weak matrix element, we adopt one-boson-exchange interactions coming from vector mesons (rho 0 and ω) as well as Z-boson. (author)

  12. Photodynamic inactivation of bacteria using polyethylenimine-chlorin(e6) conjugates: Effect of polymer molecular weight, substitution ratio of chlorin(e6) and pH.

    Science.gov (United States)

    Huang, Liyi; Zhiyentayev, Timur; Xuan, Yi; Azhibek, Dulat; Kharkwal, Gitika B; Hamblin, Michael R

    2011-04-01

    Antimicrobial photodynamic therapy (APDT) is a novel technique to treat local infections. Previously we reported that the attachment of chlorin(e6) to polyethylenimine (PEI) polymers to form PEI-ce6 conjugates is an effective way to improve ce6 PDT activity against bacteria. The aim of this work was to explore how the polymer molecular weight, substitution ratio (SR) of ce6 and pH value affect the PDT efficacy. We have synthesized PEI-ce6(10) (MW = 60,000, SR = 1) and PEI-ce6(11) (MW = 60,000, SR = 5) and compared these with the previous PEI-ce6(9) (MW = 10,000, SR = 1). We tested the PDT efficacy of these three conjugates against Gram-negative E. coli and Gram-positive bacteria (S. aureus and E. fecalis) at three different pH values (5.0, 7.4, 10.0) that may affect the charge on both the bacterial cells and on the conjugate (that has both basic and acidic groups). PEI-ce6(9) and PEI-ce6(10) were the most effective against these tested bacteria. The PDT effect of all three conjugates depended on pH values. The effective order was pH = 10.0 > pH = 7.4 > pH = 5.0 on E. coli. For S. aureus and E. fecalis the order was pH = 5.0 > pH = 10.0 > pH = 7.4. PEI-ce6(11) PDT activity was worse than PEI-ce6(10) activity which is probably connected to the fact that ce6 molecules are self-quenched within the PEI-ce6(11) molecule. Ce6 quenching within the PEI-ce6 molecules was proved by analyzing fluorescence spectra of PEI-ce6 conjugates at different pH values. There were no differences in bacterial uptake between different pH values in three PEI-ce6 conjugates. We assume high pH (rather than low pH as was hypothesized) disaggregates the conjugates, so the higher pH was more effective than the lower pH against E. coli. But for Gram-positive bacteria, low pH was more effective possibly due to more overall positive charge on the conjugate. Copyright © 2011 Wiley-Liss, Inc.

  13. Study by the disco method of critical components of a P.W.R. normal feedwater system

    International Nuclear Information System (INIS)

    Duchemin, B.; Villeneuve, M.J. de; Vallette, F.; Bruna, J.G.

    1983-03-01

    The DISCO (Determination of Importance Sensitivity of COmponents) method objectif is to rank the components of a system in order to obtain the most important ones versus availability. This method uses the fault tree description of the system and the cut set technique. It ranks the components by ordering the importances attributed to each one. The DISCO method was applied to the study of the 900 MWe P.W.R. normal feedwater system with insufficient flow in steam generator. In order to take account of operating experience several data banks were used and the results compared. This study allowed to determine the most critical component (the turbo-pumps) and to propose and quantify modifications of the system in order to improve its availability

  14. Grip strength as a frailty diagnostic component in geriatric inpatients

    Directory of Open Access Journals (Sweden)

    Dudzińska-Griszek J

    2017-07-01

    Full Text Available Joanna Dudzińska-Griszek, Karolina Szuster, Jan Szewieczek Department of Geriatrics, School of Health Sciences in Katowice, Medical University of Silesia, Katowice, Poland Background: Frailty has emerged as a key medical syndrome predictive of comorbidity, disability, institutionalization and death. As a component of the five frailty phenotype diagnostic criteria, patient grip strength deserves attention as a simple and objective measure of the frailty syndrome. The aim of this study was to assess conditions that influence grip strength in geriatric inpatients.Patients and methods: The study group consisted of 80 patients aged 78.6±7.0 years ( X ± SD, with 68.8% women, admitted to the Department of Geriatrics. A comprehensive geriatric assessment was complemented with assessment for the frailty phenotype as described by Fried et al for all patients in the study group. Functional assessment included Barthel Index of Activities of Daily Living (Barthel Index, Instrumental Activities of Daily Living Scale and Mini-Mental State Examination.Results: Three or more frailty criteria were positive in 32 patients (40%, while 56 subjects (70% fulfilled the frailty criterion of weakness (grip strength test. Multivariate linear regression analysis revealed that two independent measures showed positive association with grip strength – Mini-Mental State Examination score (β=0.239; P=0.001 and statin use (β=0.213; P=0.002 – and four independent measures were negatively associated with grip strength – female sex (β=–0.671; P<0.001, C-reactive protein (β=–0.253; P<0.001, prior myocardial infarction (β=–0.190; P=0.006 and use of an antidepressant (β=–0.163; P=0.018. Low physical activity was identified as the only independent qualitative frailty component associated with 2-year mortality in multivariate logistic regression analysis after adjustment for age and sex (odds ratio =6.000; 95% CI =1.357–26.536; P=0.018.Conclusion: Cognitive

  15. Effects of Mineral N and P Fertilizers on Yield and Yield Components of Flooded Lowland Rice on Vertisols of Fogera Plain, Ethiopia

    Directory of Open Access Journals (Sweden)

    Heluf Gebrekidan

    2006-10-01

    Full Text Available Despite its very recent history of cultivation in Ethiopia, rice is one of the potential grain crops that could contribute to the efforts for the realization of food security in the country. However, the scientific information available with regards to the response of flooded rice to N and P fertilizers for its optimum production on Vertisols of Fogera Plain is very limited. Therefore, a field experiment was conducted on Vertisols of Fogera plain, northern Ethiopia to study the yield and yield components response of rice and to establish the optimum N and P fertilizer levels required for improved grain yield of flooded rice. Six levels of N (0, 30, 60, 90, 120 and 150 kg ha−1 and five levels of P (0, 13.2, 26.4, 39.6 and 52.8 kg ha−1 laid down in a randomized complete block design with four replications were used as treatments. Nitrogen was applied in two equal splits (50% basal and 50% at maximum tillering as urea and the entire dose of P was applied basal as triple super phosphate at sowing. The main effects of N and P fertilizer levels showed significant differences (P ≤ 0.01 for all yield and yield components studied. The effects of N by P interaction were significant only for grain yield (P ≤ 0.05, number of panicles per m2 (P ≤ 0.01, number of spikelets per panicle (P ≤ 0.05 and plant height (P ≤ 0.01 among the different yield and yield components studied. Application of N and P significantly (P ≤ 0.01 increased grain yield of rice up to the levels of 60 kg N and 13.2 kg P ha−1. However, maximum grain yield (4282 kg ha−1 was obtained with the combined application of 60 kg N and 13.2 kg P ha−1, and the yield advantage over the control was 38.49% (1190 kg ha−1. Moreover, application of both N and P fertilizers have increased the magnitudes of the important yield attributes including number of panicles per m2, number of spikelets per panicle, panicle length, dry matter accumulation, straw yield and plant height

  16. The association between gastroesophageal reflux disease and recurrent respiratory papillomatosis: A systematic review.

    Science.gov (United States)

    San Giorgi, Michel R M; Helder, Herman M; Lindeman, Robbert-Jan S; de Bock, Geertruida H; Dikkers, Frederik G

    2016-10-01

    Antireflux therapy is incorporated in many treatment protocols for recurrent respiratory papillomatosis (RRP) because gastroesophageal reflux (GERD) is thought to worsen the disease course of RRP. It is unclear if GERD really aggravates the disease course. The aims of this systematic review were to 1) evaluate incidence of GERD among RRP patients and 2) report if GERD changes the clinical course or tissue properties of RRP. A search was conducted in PubMed, Embase, and Google Scholar, following the methods of Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Articles with original data, published after January 1, 1990, on RRP with GERD as a determinant were eligible. There was no language restriction. Data on study design, study population, statistics, outcomes (incidence and influence of GERD), and risk of bias were collected and evaluated following PRISMA protocols. Of 1,277 articles, 19 were selected. Gastroesophageal reflux was objectified in 25% to 100% of RRP patients. Subjective GERD was present in 0% to 70% of patients. There is no proof that GERD aggravated the clinical course or tissue properties of RRP, as measured by the number of surgeries, severity scoring systems, or dysplasia. One study did find a higher chance of web formation in patients with anterior or posterior glottic papillomas who did not receive antireflux therapy, but these results should be interpreted with care due to the study's quality. There is insufficient proof that GERD does or does not aggravate the clinical course or tissue properties of RRP. Laryngoscope, 126:2330-2339, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  17. Partial suppression of the respiratory defect of qrs1/her2 glutamyl-tRNA amidotransferase mutants by overexpression of the mitochondrial pentatricopeptide Msc6p.

    Science.gov (United States)

    Moda, Bruno S; Ferreira-Júnior, José Ribamar; Barros, Mario H

    2016-08-01

    Recently, a large body of evidences indicates the existence in the mitochondrial matrix of foci that contain different proteins involved in mitochondrial RNA metabolism. Some of these proteins have a pentatricopeptide repeat motif that constitutes their RNA-binding structures. Here we report that MSC6, a mitochondrial pentatricopeptide protein of unknown function, is a multi copy suppressor of mutations in QRS1/HER2 a component of the trimeric complex that catalyzes the transamidation of glutamyl-tRNAQ to glutaminyl-tRNAQ. This is an essential step in mitochondrial translation because of the lack of a specific mitochondrial aminoacyl glutaminyl-tRNA synthetase. MSC6 over-expression did not abolish translation of an aberrant variant form of Cox2p detected in QRS1/HER2 mutants, arguing against a suppression mechanism that bypasses Qrs1p function. A slight decrement of the mitochondrial translation capacity as well as diminished growth on respiratory carbon sources media for respiratory activity was observed in the msc6 null mutant. Additionally, the msc6 null mutant did not display any impairment in RNA transcription, processing or turnover. We concluded that Msc6p is a mitochondrial matrix protein and further studies are required to indicate the specific function of Msc6p in mitochondrial translation.

  18. Low-level laser therapy equipment needs calibration before clinical use

    Science.gov (United States)

    Machado de Senna, André; Machado-de-sena, Rosa Maria; Facundes, Arseni Lázaro; Barros Nepomuceno, Patrícia; Sávya Florentino, Wanilza; Olegário de Araújo, Ronyere

    2018-04-01

    Many factors can influence the radiant power delivered by the low-level laser therapy (LLLT) equipment, such as its cleaning and condition, as well as the use of plastic films for protecting the laser or even its time of use. Radiant power is an important factor to consider because it affects the amount of energy delivered to the target tissue. The difference between real radiant power (RRP) and nominal radiant power (NRP) may interfere in the expected results, because the delivered energy is different from the desired energy. Purpose: The objective of this study was to compare the NRP with the RRP offered by LLLT devices under clinical conditions of use. Material and Methods: For data collection to this study, 61 LLLT devices used in private and public dental practices in the state of Tocantins, Brazil, were evaluated. Three consecutive power measurements were performed at one-minute intervals and then the average of the measured power was calculated. The RRP was compared to the NRP. Results: The equipment presented NRP from 30 to 500mW while RRP ranged from 17.3 to 107.0mW. Discussion and Conclusion: The mean power measured in clinical conditions of use of the laser equipment was different from the nominal power reported by the manufacturers of the devices (p<0,01). The RRP ranged between 12.92% and 107% of NRP. This fact is worrisome, since one of the most important parameters for the success of the treatment of an injury using LLLT is the energy (power x time) delivered. These findings reinforce the need of calibrating the equipment before each laser application in order to avoid failures in the therapeutic conduct.

  19. The auditory-evoked N2 and P3 components in the stop-signal task: indices of inhibition, response-conflict or error-detection?

    Science.gov (United States)

    Dimoska, Aneta; Johnstone, Stuart J; Barry, Robert J

    2006-11-01

    The N2 and P3 components have been separately associated with response inhibition in the stop-signal task, and more recently, the N2 has been implicated in the detection of response-conflict. To isolate response inhibition activity from early sensory processing, the present study compared processing of the stop-signal with that of a task-irrelevant tone, which subjects were instructed to ignore. Stop-signals elicited a larger N2 on failed-stop trials and a larger P3 on successful-stop trials, relative to ignore-signal trials, likely reflecting activity related to failed and successful stopping, respectively. ERPs between fast and slow reaction-time (RT) groups were also examined as it was hypothesised that greater inhibitory activation to stop faster responses would manifest in the component reflecting this process. Successful-stop P3 showed the anticipated effect (globally larger amplitude in the fast than slow RT group), supporting its association with the stopping of an ongoing response. In contrast, N2 was larger in the slow than fast RT group, and in contrast to the predictions of the response-conflict hypothesis, successful-stop N2 and the response-locked error-negativity (Ne) differed in scalp distribution. These findings indicate that the successful-stop N2 may be better explained as a deliberate form of response control or selection, which the slow RT group employed as a means of increasing the likelihood of a successful-stop. Finally, a comparison of stimulus and response-locked ERPs revealed that the failed-stop N2 and P3 appeared to reflect error-related activity, best observed in the response-locked Ne and error-positivity (Pe). Together these findings indicate that the successful-stop N2 and P3 reflect functionally distinct aspects of response control that are dependent upon performance strategies, while failed-stop N2 and P3 reflect error-related activity.

  20. Wolf-Hirschhorn (4p-) syndrome: prenatal diagnosis, molecular cytogenetic characterization and association with a 1.2-Mb microduplication at 8p22-p21.3 and a 1.1-Mb microduplication at 10p15.3 in a fetus with an apparently pure 4p deletion.

    Science.gov (United States)

    Chen, Chih-Ping; Su, Yi-Ning; Chen, Yi-Yung; Su, Jun-Wei; Chern, Schu-Rern; Chen, Yu-Ting; Chen, Wen-Lin; Chen, Li-Feng; Wang, Wayseen

    2011-12-01

    To present prenatal diagnosis and molecular cytogenetic characterization of Wolf-Hirschhorn syndrome (WHS) associated with microduplications at 8p and 10p in a fetus with an apparently pure 4p deletion. A 35-year-old gravida 2, para 1 woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Her husband was 38 years of age. There was no family history of congenital malformations. Amniocentesis revealed a karyotype of 46,XY,del(4p16.1). The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis revealed a 6.5-Mb deletion at 4p16.3-p16.1, a 1.2-Mb microduplication at 8p22-p21.3, and a 1.1-Mb microduplication at 10p15.3, or arr cgh 4p16.3p16.1 (0-6,531,998 bp)×1, 8p22p21.3 (18,705,388-19,940,445 bp)×3, 10p15.3 (0-1,105,065 bp)×3. Polymorphic DNA marker analysis confirmed a paternal origin of 4p deletion. Prenatal ultrasound revealed facial dysmorphism and hypospadias. The aCGH analysis of the parents revealed no genomic imbalance. Fluorescence in situ hybridization study showed an unbalanced reciprocal translocation between chromosomes 4 and 10 at bands 4p16.1 and 10p15.3. The cytogenetic result, thus, was 46,XY,der(4)t(4;10)(p16.1;p15.3),dup(8)(p21.3p22). The parents elected to terminate the pregnancy, and a 470-g malformed fetus was delivered. The present case provides evidence that an apparently pure 4p deletion can be associated with subtle chromosome imbalances in other chromosomes. Copyright © 2011. Published by Elsevier B.V.

  1. Diagnostic performance of I-123-labeled serum amyloid P component scintigraphy in patients with amyloidosis

    NARCIS (Netherlands)

    Hazenberg, BPC; van Rijswijk, MH; Piers, DA; Lub-de Hooge, MN; Vellenga, E; Haagsma, EB; Hawkins, PN; Jager, PL

    Purpose: To assess the diagnostic accuracy and additional information provided by I-123-labeled serum amyloid P component ( SAP) scintigraphy in patients with systemic and localized amyloidosis. Subjects and Methods: I-123-labeled human SAP was injected intravenously into 20 controls and 189

  2. Antioxidant activity of Sempervivum tectorum and its components.

    Science.gov (United States)

    Sentjurc, Marjeta; Nemec, Marjana; Connor, Henry D; Abram, Veronika

    2003-04-23

    The antioxidant properties of components of leaf extracts of the evergreen plant, Sempervivum tectorum (ST), have been evaluated using UV irradiated liposomal systems containing the spin trap 5-(diethoxyphosphoryl)-5-methyl-pyrroline-N-oxide. Decreases in free radical activity in the liposomal systems as measured by electron paramagnetic resonance (EPR) spectroscopy demonstrate that the lipophilic ST juice components, kaempferol (KA) and kaempferol-3-glucoside (KG) contribute significantly to the antioxidant properties of the juice. EPR spectral simulation established the presence of oxygen and carbon centered free radical adducts. The mixtures with low pH, citric and malic acid, and ST juice reveal increased EPR signals from oxygen centered radicals in comparison to the control, pointing to the important role of pH in oxygen radical formation. Parallel assays that measured thiobarbituric acid related substances confirm the antioxidant effects of KA and KG and explain the results of spin trapping experiments complicated by low pH's.

  3. The Role of ARF6 in Biliary Atresia.

    Directory of Open Access Journals (Sweden)

    Mylarappa Ningappa

    Full Text Available Altered extrahepatic bile ducts, gut, and cardiovascular anomalies constitute the variable phenotype of biliary atresia (BA.To identify potential susceptibility loci, Caucasian children, normal (controls and with BA (cases at two US centers were compared at >550000 SNP loci. Systems biology analysis was carried out on the data. In order to validate a key gene identified in the analysis, biliary morphogenesis was evaluated in 2-5-day post-fertilization zebrafish embryos after morpholino-antisense oligonucleotide knockdown of the candidate gene ADP ribosylation factor-6 (ARF6, Mo-arf6.Among 39 and 24 cases at centers 1 and 2, respectively, and 1907 controls, which clustered together on principal component analysis, the SNPs rs3126184 and rs10140366 in a 3' flanking enhancer region for ARF6 demonstrated higher minor allele frequencies (MAF in each cohort, and 63 combined cases, compared with controls (0.286 vs. 0.131, P = 5.94x10-7, OR 2.66; 0.286 vs. 0.13, P = 5.57x10-7, OR 2.66. Significance was enhanced in 77 total cases, which included 14 additional BA genotyped at rs3126184 only (p = 1.58x10-2, OR = 2.66. Pathway analysis of the 1000 top-ranked SNPs in CHP cases revealed enrichment of genes for EGF regulators (p<1 x10-7, ERK/MAPK and CREB canonical pathways (p<1 x10-34, and functional networks for cellular development and proliferation (p<1 x10-45, further supporting the role of EGFR-ARF6 signaling in BA. In zebrafish embryos, Mo-arf6 injection resulted in a sparse intrahepatic biliary network, several biliary epithelial cell defects, and poor bile excretion to the gall bladder compared with uninjected embryos. Biliary defects were reproduced with the EGFR-blocker AG1478 alone or with Mo-arf6 at lower doses of each agent and rescued with arf6 mRNA.The BA-associated SNPs identify a chromosome 14q21.3 susceptibility locus encompassing the ARF6 gene. arf6 knockdown in zebrafish implicates early biliary dysgenesis as a basis for BA, and also

  4. Measurements of spin parameters in p-p elastic scattering at 6 GeV/c

    International Nuclear Information System (INIS)

    Linn, S.L.; Perlmutter, A.; Crosbie, E.A.; Ratner, L.G.; Schultz, P.F.; O'Fallon, J.R.; Cameron, P.R.; Crabb, D.G.; Fernow, R.C.; Hansen, P.H.; Krisch, A.D.; Salthouse, A.J.; Sandler, B.; Shima, T.; Terwilliger, K.M.

    1982-01-01

    We measured the differential cross section for proton-proton elastic scattering in 6 GeV/c, with both initial spins oriented normal to the scattering plane. The analyzing power A shows significant structure with a large broad peak reaching about 24% near P/sub perpendicular/ 2 = 1.6 (GeV/c) 2 . The spin-spin correlation parameter A/sub n/n exhibits more dramatic structure, with a small but very sharp peak rising rapidly to about 13% at 90 0 /sub tsc.m./. This sharp peak may be caused by particle-identity effects

  5. Preclinical evaluation of [{sup 18}F]2FNQ1P as the first fluorinated serotonin 5-HT{sub 6} radioligand for PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Guillaume [Universite Claude Bernard Lyon 1, CNRS INSERM, Lyon Neuroscience Research Center, Lyon (France); Hospices Civils de Lyon, Lyon (France); Colomb, Julie [Universite Claude Bernard Lyon 1, CNRS, Institute of Chemistry and Biochemistry, Villeurbanne (France); Sgambato-Faure, Veronique; Tremblay, Leon [Universite Claude Bernard Lyon 1, CNRS, Cognitive Neuroscience Center, Bron (France); Billard, Thierry [Universite Claude Bernard Lyon 1, CNRS, Institute of Chemistry and Biochemistry, Villeurbanne (France); CERMEP-Imaging Platform, Groupement Hospitalier Est, Lyon (France); Zimmer, Luc [Universite Claude Bernard Lyon 1, CNRS INSERM, Lyon Neuroscience Research Center, Lyon (France); Hospices Civils de Lyon, Lyon (France); CERMEP-Imaging Platform, Groupement Hospitalier Est, Lyon (France)

    2014-10-21

    Brain serotonin 6 receptor (5-HT{sub 6}) is one of the most recently identified serotonin receptors. It is a potent therapeutic target for psychiatric and neurological diseases, e.g. schizophrenia and Alzheimer's disease. Since no specific fluorinated radioligand has yet been successfully used to study this receptor by positron emission tomography (PET) neuroimaging, the objective of the present study was to study the first 5-HT{sub 6} {sup 18}F-labelled radiotracer. 2FNQ1P, inspired by the quinolone core of a previous radiotracer candidate, GSK215083, was selected according its 5-HT{sub 6} affinity and selectivity and was radiolabelled by {sup 18}F nucleophilic substitution. The cerebral distribution of [{sup 18}F]2FNQ1P was studied in vivo in rats, cats and macaque monkeys. The chemical and radiochemical purities of [{sup 18}F]2FNQ1P were >98 %. In rats, in vitro competition with the 5-HT{sub 6} antagonist, SB258585, revealed that the radioligand was displaced dose dependently. Rat microPET studies showed low brain uptake of [{sup 18}F]2FNQ1P, reversed by the P-glycoprotein inhibitor, cyclosporin. On the contrary, PET scans in cats showed good brain penetration and specific striatal binding blocked after pretreatment with unlabelled 2FNQ1P. PET scans in macaque monkeys confirmed high specific binding in both cortical and subcortical regions, specifically decreased by pretreatment with the 5-HT{sub 6} receptor antagonist, SB258585. 2FNQ1P was initially selected because of its suitable characteristics for 5-HT{sub 6} receptor probing in vitro in terms of affinity and specificity. Although in vivo imaging in rats cannot be considered as predictive of the clinical characteristics of the radiotracer, [{sup 18}F]2FNQ1P appeared to be a suitable 5-HT{sub 6} PET tracer in feline and primate models. These preclinical results encourage us to pursue the clinical development of this first fluorinated 5-HT{sub 6} PET radiotracer. (orig.)

  6. Identification of SNPs involved in regulating a novel alternative transcript of P450 CYP6ER1 in the brown planthopper.

    Science.gov (United States)

    Liang, Zhi-Kun; Pang, Rui; Dong, Yi; Sun, Zhong-Xiang; Ling, Yan; Zhang, Wen-Qing

    2017-04-29

    Cytochrome P450-mediated metabolic resistance is one of the major mechanisms involved in insecticide resistance. Although the up-regulation of cytochrome P450 plays a vital role in insecticide metabolism, the molecular basis for the transcriptional regulation of cytochrome P450 remains largely unknown. The P450 gene CYP6ER1, has been reported to confer imidacloprid resistance to the brown planthopper, Nilaparvata lugens. Here, we identified a novel alternative transcript of CYP6ER1 (transcript A2) that had different expression patterns between resistant and susceptible populations, and was more stable after insecticide induction. The promoter of this transcript was sequenced and multiple single nucleotide polymorphisms (SNPs) were detected in individuals from susceptible and resistant field-collected populations. Resistant alleles of four SNPs were found to significantly enhance the promoter activity of the CYP6ER1 transcript A2. Electrophoretic mobility shift assays (EMSAs) revealed that these SNPs might regulate the binding of transcription factors to the promoter. Our findings provide novel evidence regarding the transcriptional regulation of a metabolic resistance-related gene and may be useful to understand the resistance mechanism of N. lugens in the field. © 2017 Institute of Zoology, Chinese Academy of Sciences.

  7. Molecular and functional characterization of CYP6BQ23, a cytochrome P450 conferring resistance to pyrethroids in European populations of pollen beetle, Meligethes aeneus.

    Science.gov (United States)

    Zimmer, Christoph T; Bass, Chris; Williamson, Martin S; Kaussmann, Martin; Wölfel, Katharina; Gutbrod, Oliver; Nauen, Ralf

    2014-02-01

    The pollen beetle (Meligethes aeneus F.) is widespread throughout much of Europe where it is a major coleopteran pest of oilseed rape (Brassica napus). The reliance on synthetic insecticides for control, particularly the pyrethroid class, has led to the development of populations with high levels of resistance. Resistance to pyrethroids is now widespread throughout Europe and is thought to be mediated by enhanced detoxification by cytochrome P450ś and/or mutation of the pyrethroid target-site, the voltage-gated sodium channel. However, in the case of cytochrome P450 mediated detoxification, the specific enzyme(s) involved has (have) not yet been identified. In this study a degenerate PCR approach was used to identify ten partial P450 gene sequences from pollen beetle. Quantitative PCR was then used to examine the level of expression of these genes in a range of pollen beetle populations that showed differing levels of resistance to pyrethroids in bioassays. The study revealed a single P450 gene, CYP6BQ23, which is significantly and highly overexpressed (up to ∼900-fold) in adults and larvae of pyrethroid resistant strains compared to susceptible strains. CYP6BQ23 overexpression is significantly correlated with both the level of resistance and with the rate of deltamethrin metabolism in microsomal preparations of these populations. Functional recombinant expression of full length CYP6BQ23 along with cytochrome P450 reductase in an insect (Sf9) cell line showed that it is able to efficiently metabolise deltamethrin to 4-hydroxy deltamethrin. Furthermore we demonstrated by detection of 4-hydroxy tau-fluvalinate using ESI-TOF MS/MS that functionally expressed CYP6BQ23 also metabolizes tau-fluvalinate. A protein model was generated and subsequent docking simulations revealed the predicted substrate-binding mode of both deltamethrin and tau-fluvalinate to CYP6BQ23. Taken together these results strongly suggest that the overexpression of CYP6BQ23 is the primary

  8. Integrin αβ1, αvβ, α6β effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

    International Nuclear Information System (INIS)

    Sansing, Hope A.; Sarkeshik, Ali; Yates, John R.; Patel, Vyomesh; Gutkind, J. Silvio; Yamada, Kenneth M.; Berrier, Allison L.

    2011-01-01

    Research highlights: → Proteomics of clustered integrin αβ1, α v β, α 6 β receptors in oral carcinoma. → p130Cas, Dek, Src and talin regulate oral carcinoma invasion. → p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomics screen of proteins recruited to clustered integrin αβ1, α v β or α 6 β receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.

  9. MSH6 Mutations are Frequent in Hereditary Nonpolyposis Colorectal Cancer Families With Normal pMSH6 Expression as Detected by Immunohistochemistry

    DEFF Research Database (Denmark)

    Okkels, Henrik; Larsen, K.L.; Thorlacius-Ussing, O.

    2012-01-01

    INTRODUCTION:: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition accounting for 2% to 4% of all colorectal cancer cases worldwide. Families with germ line mutations in 1 of 6 mismatch repair genes are known as Lynch syndrome families. The largest number...... this approach in Lynch families carrying mutations in MSH6. MATERIALS AND METHODS:: Results of the screening of the MSH6 gene in HNPCC families were compared with those obtained on immunohistochemical protein analysis. RESULTS:: In 56 (7%) of 815 families, at least 1 MSH6 mutation, 23 definitively pathogenic...... be detected, whereas in 34.5% pMSH6 was present and pMLH1/pPMS2 was absent. CONCLUSIONS:: If genetic screening of HNPCC families depended on immunohistochemical results, a substantial number of families harboring a pathogenic mutation in MSH6 and the vast majority of families harboring an MSH6 unclassified...

  10. The biodistribution and imaging of a novel amyloid probe 131I-serum amyloid P-component in mice model of amyloidosis

    International Nuclear Information System (INIS)

    Wei Hailiang; Zhang Chunli; Wang Rongfu; Zhang Jianhua; Yan Ping; Kang Lei; Guo Fengqin

    2011-01-01

    Objective: To validate 131 I-serum amyloid P-component (SAP) as a novel amyloid probe in mice bearing amyloidosis and evaluate its diagnostic value. Methods: Standard SAP was labeled with 131 I using Iodogen method. Amyloidotic mice model was established by subcutaneous injection of 0.5 ml 10% Casein daily for 21 d, and the control group was injected with 0.5 ml saline. Both groups were injected with 7.4 MBq 131 I-SAP through the tail veins and imaging was performed at 1, 3, 6, 24, 48 and 72 h post injection. In biodistribution study, 30 amyloidotic mice model and 30 controls were injected with 555 kBq 131 I-SAP and were killed evenly at 1, 3, 6, 24, 48 and 72 h post injection. T test was used to analysis the data. Results: The labeling efficiency of 131 I-SAP was 70.6%, and the radiochemical purity was ( 95.5 ±3.4)%. There was significant tracer uptake by liver, spleen and kidney at 24 h in the test group and mild uptake by these organs in the control group. The uptake ratios of liver, spleen and kidney over blood in the test group were 2.201 ±0.301, 2.139 ±0.223, 4.797 ±0.615, vs 0.657 ±0.126, 1.014 ±0.063, 0.607 ±0.028 in the control group,respectively (t=10.747, 11.626 and 15.135, all P<0.01). The uptake differences between the two groups were still statistically significant at 48 h (t=15.128, 4.558, 16.960, all P<0.01). The uptake ratios of spleen over blood between the two groups were not significantly different at 72 h (t=3.022, P>0.05), but the other two uptake ratios were both significantly different (t=7.801, 6.442, both P<0.01). Conclusions: SAP can be reliably labeled with 131 I. The labeled product 131 I-SAP can accumulate in amyloid laden tissues, thus rendering it a potential agent in the detection of amyloidosis. (authors)

  11. Air pollution and doctors' house calls: results from the ERPURS system for monitoring the effects of air pollution on public health in Greater Paris, France, 1991-1995. Evaluation des Risques de la Pollution Urbaine pour la Santé.

    Science.gov (United States)

    Medina, S; Le Tertre, A; Quénel, P; Le Moullec, Y; Lameloise, P; Guzzo, J C; Festy, B; Ferry, R; Dab, W

    1997-10-01

    This study examines short-term relationships between doctors' house calls and urban air pollution in Greater Paris for the period 1991-1995. Poisson regressions using nonparametric smoothing functions controlled for time trend, seasonal patterns, pollen counts, influenza epidemics, and weather. The relationship between asthma visits and air pollution was stronger for children. A relative risk (RRP95/P5) of 1.32 [95% confidence interval (CI) = 1.17-1.47)] was observed for an increase from the 5th to the 95th percentile (7-51 micrograms/m3) in daily concentrations of black smoke (BS). The risks for 24-hr sulfur dioxide and nitrogen dioxide levels were in the same range. Cardiovascular conditions, considered globally, showed weaker associations than angina pectoris/myocardial infarction, for which RRP95/P5 was 1.63 (95% CI = 1.10-2.41) in relation to ozone ambient levels. Eye conditions were exclusively related to ozone (RRP95/P5 = 1.17, 95% CI 1.02-1.33). Asthma visits and ozone showed an interaction with minimum temperature: an effect was observed only at 10 degrees C or higher. In two-pollutant models including BS with, successively, SO2, NO2, and O3, only BS and O3 effects remained stable. Along with mortality and hospital admissions, house call activity data, available on a regular basis, may be a sensitive indicator for monitoring health effects related to air pollution.

  12. Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells.

    Science.gov (United States)

    Rusin, Scott F; Schlosser, Kate A; Adamo, Mark E; Kettenbach, Arminja N

    2015-10-13

    Protein phosphorylation is an important regulatory mechanism controlling mitotic progression. Protein phosphatase 6 (PP6) is an essential enzyme with conserved roles in chromosome segregation and spindle assembly from yeast to humans. We applied a baculovirus-mediated gene silencing approach to deplete HeLa cells of the catalytic subunit of PP6 (PP6c) and analyzed changes in the phosphoproteome and proteome in mitotic cells by quantitative mass spectrometry-based proteomics. We identified 408 phosphopeptides on 272 proteins that increased and 298 phosphopeptides on 220 proteins that decreased in phosphorylation upon PP6c depletion in mitotic cells. Motif analysis of the phosphorylated sites combined with bioinformatics pathway analysis revealed previously unknown PP6c-dependent regulatory pathways. Biochemical assays demonstrated that PP6c opposed casein kinase 2-dependent phosphorylation of the condensin I subunit NCAP-G, and cellular analysis showed that depletion of PP6c resulted in defects in chromosome condensation and segregation in anaphase, consistent with dysregulation of condensin I function in the absence of PP6 activity. Copyright © 2015, American Association for the Advancement of Science.

  13. [Energy pooling collisions for K(4P) + Cs(5D) in a K-Cs mixture].

    Science.gov (United States)

    Aihemaiti, Pulati; Dai, Kang; Lu, Xin-hong; Shen, Yi-fan

    2005-04-01

    The rate coefficients for energy-pooling collisions K(4P) + Cs(5D) --> Cs(6S) + K(4D, 6S) in the K-Cs vapor mixture were measured relative to a known energy-pooling rate coefficient of a homonuclear reaction [i. e., Cs(6P) + Cs(5D) --> Cs(6S) + Cs (7D(J))]. Populations of the Cs(6P, 5D) and K(4P) states were produced by photodissociation of K2 and Cs2 molecules through the use of a dye laser radiation. The resulting fluorescence included the direct components emitted in the decay of the excited states produced by photodissociation and the induced components arising from the collisionally populated states. By combining relative intensities of the components with the effective lifetimes of Cs(6P) and K(4P) states, the rate coefficients (in units of 10(-9) cm3 x s(-1)) for the heteronuclear energy-pooling were found to be 2.6 and 3.6, respectively. The contribution to the rate coefficients from other processes are discussed.

  14. Characterization of P1 promoter activity of the β-galactoside α2,6 ...

    Indian Academy of Sciences (India)

    2012-04-05

    Apr 5, 2012 ... The level of β-galactoside α2,6-sialyltransferase I (ST6Gal I) mRNA, encoded by the gene siat1, is increased in malignant tissues. Expression is regulated by different promoters – P1, P2 and P3 – generating three mRNA isoforms. H, X and YZ. In cervical cancer tissue the mRNA isoform H, which results ...

  15. A P,O,P′-tridentate mixed-donor scorpionate ligand: 6-[4,6-bis(diphenylphosphino-10H-phenoxazin-10-yl]hexan-1-ol

    Directory of Open Access Journals (Sweden)

    Holger B. Friedrich

    2008-10-01

    Full Text Available The title compound, C42H39NO2P2, is a P,O,P′-tridentate scorpionate-type ligand and has one molecule in the asymmetric unit. The angles involving the P atoms range from 100.21 (7 to 104.89 (7°. The N-hexanol group was found to be disordered and was refined over two positions with final occupancies of 0.683 (3 and 0.317 (3 which affected the C—O and C—N bond lengths. The bond lengths for C—O range from 1.402 (2 to 1.415 (2 Å and for C—N from 1.410 (2 to 1.448 (3 Å for the major disorder component; the corresponding ranges for the minor disorder component are 1.429 (3–1.408 (3 and 1.474 (3–1.474 (4 Å.

  16. Comparative live-cell imaging analyses of SPA-2, BUD-6 and BNI-1 in Neurospora crassa reveal novel features of the filamentous fungal polarisome.

    Directory of Open Access Journals (Sweden)

    Alexander Lichius

    Full Text Available A key multiprotein complex involved in regulating the actin cytoskeleton and secretory machinery required for polarized growth in fungi, is the polarisome. Recognized core constituents in budding yeast are the proteins Spa2, Pea2, Aip3/Bud6, and the key effector Bni1. Multicellular fungi display a more complex polarized morphogenesis than yeasts, suggesting that the filamentous fungal polarisome might fulfill additional functions. In this study, we compared the subcellular organization and dynamics of the putative polarisome components BUD-6 and BNI-1 with those of the bona fide polarisome marker SPA-2 at various developmental stages of Neurospora crassa. All three proteins exhibited a yeast-like polarisome configuration during polarized germ tube growth, cell fusion, septal pore plugging and tip repolarization. However, the localization patterns of all three proteins showed spatiotemporally distinct characteristics during the establishment of new polar axes, septum formation and cytokinesis, and maintained hyphal tip growth. Most notably, in vegetative hyphal tips BUD-6 accumulated as a subapical cloud excluded from the Spitzenkörper (Spk, whereas BNI-1 and SPA-2 partially colocalized with the Spk and the tip apex. Novel roles during septal plugging and cytokinesis, connected to the reinitiation of tip growth upon physical injury and conidial maturation, were identified for BUD-6 and BNI-1, respectively. Phenotypic analyses of gene deletion mutants revealed additional functions for BUD-6 and BNI-1 in cell fusion regulation, and the maintenance of Spk integrity. Considered together, our findings reveal novel polarisome-independent functions of BUD-6 and BNI-1 in Neurospora, but also suggest that all three proteins cooperate at plugged septal pores, and their complex arrangement within the apical dome of mature hypha might represent a novel aspect of filamentous fungal polarisome architecture.

  17. Label-free genotyping of cytochrome P450 2D6*10 using ligation-mediated strand displacement amplification with DNAzyme-based chemiluminescence detection.

    Science.gov (United States)

    Wang, Hong-Qi; Wu, Zhan; Zhang, Yan; Tang, Li-Juan; Yu, Ru-Qin; Jiang, Jian-Hui

    2012-01-13

    Genotyping of cytochrome P450 monooxygenase 2D6*10 (CYP2D6*10) plays an important role in pharmacogenomics, especially in clinical drug therapy of Asian populations. This work reported a novel label-free technique for genotyping of CYP2D6*10 based on ligation-mediated strand displacement amplification (SDA) with DNAzyme-based chemiluminescence detection. Discrimination of single-base mismatch is firstly accomplished using DNA ligase to generate a ligation product. The ligated product then initiates a SDA reaction to produce aptamer sequences against hemin, which can be probed by chemiluminescence detection. The proposed strategy is used for the assay of CYP2D6*10 target and the genomic DNA. The results reveal that the proposed technique displays chemiluminescence responses in linear correlation to the concentrations of DNA target within the range from 1 pM to 1 nM. A detection limit of 0.1 pM and a signal-to-background ratio of 57 are achieved. Besides such high sensitivity, the proposed CYP2D6*10 genotyping strategy also offers superb selectivity, great robustness, low cost and simplified operations due to its label-free, homogeneous, and chemiluminescence-based detection format. These advantages suggest this technique may hold considerable potential for clinical CYP2D6*10 genotyping and association studies. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. The Structure of the MAP2K MEK6 Reveals an Autoinhibitory Dimer

    Energy Technology Data Exchange (ETDEWEB)

    Min, Xiaoshan; Akella, Radha; He, Haixia; Humphreys, John M.; Tsutakawa, Susan E.; Lee, Seung-Jae; Tainer, John A.; Cobb, Melanie H.; Goldsmith, Elizabeth J.

    2009-07-13

    MAP2Ks are dual-specificity protein kinases functioning at the center of three-tiered MAP kinase modules. The structure of the kinase domain of the MAP2K MEK6 with phosphorylation site mimetic aspartic acid mutations (MEK6/{Delta}N/DD) has been solved at 2.3 {angstrom} resolution. The structure reveals an autoinhibited elongated ellipsoidal dimer. The enzyme adopts an inactive conformation, based upon structural queues, despite the phosphomimetic mutations. Gel filtration and small-angle X-ray scattering analysis confirm that the crystallographically observed ellipsoidal dimer is a feature of MEK6/{Delta}N/DD and full-length unphosphorylated wild-type MEK6 in solution. The interface includes the phosphate binding ribbon of each subunit, part of the activation loop, and a rare 'arginine stack' between symmetry-related arginine residues in the N-terminal lobe. The autoinhibited structure likely confers specificity on active MAP2Ks. The dimer may also serve the function in unphosphorylated MEK6 of preventing activation loop phosphorylation by inappropriate kinases.

  19. Hsp60 and p70S6K form a complex in human cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Kroupskaya I. V.

    2011-02-01

    Full Text Available Molecular chaperon Hsp60 and protein kinase p70S6K play an important functional role in the regulation of cardiomyocytes vital function or apoptosis. Aim. To study a possibility of in vivo complex formation between Hsp60 and p70S6K in cardiomyocytes. Methods. Co-immunoprecipitation, Western-blot analysis. Results. We have identified in vivo interaction between molecular chaperone Hsp60 and two isoforms of proteinkinase p70S6K in human myocardium, normal and affected by cardiomyopathy. Conclusions. The results obtained suggest a possible participation of molecular chaperon Hsp60 in regulation of p70S6K activity in stressinduced apoptotic signaling pathway in cardiomyocytes.

  20. Biogenic non-crystalline U(IV) revealed as major component in uranium ore deposits

    Science.gov (United States)

    Bhattacharyya, Amrita; Campbell, Kate M.; Kelly, Shelly D.; Roebbert, Yvonne; Weyer, Stefan; Bernier-Latmani, Rizlan; Borch, Thomas

    2017-06-01

    Historically, it is believed that crystalline uraninite, produced via the abiotic reduction of hexavalent uranium (U(VI)) is the dominant reduced U species formed in low-temperature uranium roll-front ore deposits. Here we show that non-crystalline U(IV) generated through biologically mediated U(VI) reduction is the predominant U(IV) species in an undisturbed U roll-front ore deposit in Wyoming, USA. Characterization of U species revealed that the majority (~58-89%) of U is bound as U(IV) to C-containing organic functional groups or inorganic carbonate, while uraninite and U(VI) represent only minor components. The uranium deposit exhibited mostly 238U-enriched isotope signatures, consistent with largely biotic reduction of U(VI) to U(IV). This finding implies that biogenic processes are more important to uranium ore genesis than previously understood. The predominance of a relatively labile form of U(IV) also provides an opportunity for a more economical and environmentally benign mining process, as well as the design of more effective post-mining restoration strategies and human health-risk assessment.

  1. Poxviral protein A52 stimulates p38 mitogen-activated protein kinase (MAPK) activation by causing tumor necrosis factor receptor-associated factor 6 (TRAF6) self-association leading to transforming growth factor β-activated kinase 1 (TAK1) recruitment.

    Science.gov (United States)

    Stack, Julianne; Hurst, Tara P; Flannery, Sinead M; Brennan, Kiva; Rupp, Sebastian; Oda, Shun-ichiro; Khan, Amir R; Bowie, Andrew G

    2013-11-22

    Vaccinia virus encodes a number of proteins that inhibit and manipulate innate immune signaling pathways that also have a role in virulence. These include A52, a protein shown to inhibit IL-1- and Toll-like receptor-stimulated NFκB activation, via interaction with interleukin-1 receptor-associated kinase 2 (IRAK2). Interestingly, A52 was also found to activate p38 MAPK and thus enhance Toll-like receptor-dependent IL-10 induction, which was TRAF6-dependent, but the manner in which A52 manipulates TRAF6 to stimulate p38 activation was unclear. Here, we show that A52 has a non-canonical TRAF6-binding motif that is essential for TRAF6 binding and p38 activation but dispensable for NFκB inhibition and IRAK2 interaction. Wild-type A52, but not a mutant defective in p38 activation and TRAF6 binding (F154A), caused TRAF6 oligomerization and subsequent TRAF6-TAK1 association. The crystal structure of A52 shows that it adopts a Bcl2-like fold and exists as a dimer in solution. Residue Met-65 was identified as being located in the A52 dimer interface, and consistent with that, A52-M65E was impaired in its ability to dimerize. A52-M65E although capable of interacting with TRAF6, was unable to cause either TRAF6 self-association, induce the TRAF6-TAK1 association, or activate p38 MAPK. The results suggest that an A52 dimer causes TRAF6 self-association, leading to TAK1 recruitment and p38 activation. This reveals a molecular mechanism whereby poxviruses manipulate TRAF6 to activate MAPKs (which can be proviral) without stimulating antiviral NFκB activation.

  2. [Decrease in N170 evoked potential component latency during repeated presentation of face images].

    Science.gov (United States)

    Verkhliutov, V M; Ushakov, V L; Strelets, V B

    2009-01-01

    The 15 healthy volunteers EEG from 28 channels was recorded during the presentation of visual stimuli in the form of face and building images. The stimuli were presented in two series. The first series consisted of 60 face and 60 building images presented in random order. The second series consisted of 30 face and 30 building images. The second series began 1.5-2 min after the end of the first ore. No instruction was given to the participants. P1, N170 and VPP EP components were identified for both stimuli categories. These components were located in the medial parietal area (Brodmann area 40). P1 and N170 components were recorded in the superior temporal fissure (Brodmann area 21, STS region), the first component had the latency 120 ms, the second one--155 ms. VPP was recorded with the latency 190 ms (Brodmann area 19). Dynamic mapping of EP components with the latency from 97 to 242 ms revealed the removal of positive maximums from occipital to frontal areas through temporal ones and their subsequent returning to occipital areas through the central ones. During the comparison of EP components to face and building images the amplitude differences were revealed in the following areas: P1--in frontal, central and anterior temporal areas, N170--in frontal, central, temporal and parietal areas, VPP--in all areas. It was also revealed that N170 latency was 12 ms shorter for face than for building images. It was proposed that the above mentioned N170 latency decrease for face in comparison with building images is connected with the different space location of the fusiform area responsible for face and building images recognition. Priming--the effect that is revealed during the repetitive face images presentation is interpreted as the manifestation of functional heterogeneity of the fusiform area responsible for the face images recognition. The hypothesis is put forward that the parts of extrastriate cortex which are located closer to the central retinotopical

  3. Rice black-streaked dwarf virus P6 self-interacts to form punctate, viroplasm-like structures in the cytoplasm and recruits viroplasm-associated protein P9-1

    Directory of Open Access Journals (Sweden)

    Yu Jialin

    2011-01-01

    Full Text Available Abstract Background Rice black-streaked dwarf virus (RBSDV, a member of the genus Fijivirus within the family Reoviridae, can infect several graminaceous plant species including rice, maize and wheat, and is transmitted by planthoppers. Although several RBSDV proteins have been studied in detail, functions of the nonstructural protein P6 are still largely unknown. Results In the current study, we employed yeast two-hybrid assays, bimolecular fluorescence complementation and subcellular localization experiments to show that P6 can self-interact to form punctate, cytoplasmic viroplasm-like structures (VLS when expressed alone in plant cells. The region from residues 395 to 659 is necessary for P6 self-interaction, whereas two polypeptides (residues 580-620 and 615-655 are involved in the subcellular localization of P6. Furthermore, P6 strongly interacts with the viroplasm-associated protein P9-1 and recruits P9-1 to localize in VLS. The P6 395-659 region is also important for the P6-P9-1 interaction, and deleting any region of P9-1 abolishes this heterologous interaction. Conclusions RBSDV P6 protein has an intrinsic ability to self-interact and forms VLS without other RBSDV proteins or RNAs. P6 recruits P9-1 to VLS by direct protein-protein interaction. This is the first report on the functionality of RBSDV P6 protein. P6 may be involved in the process of viroplasm nucleation and virus morphogenesis.

  4. Effect of mobile unidirectional air flow unit on microbial contamination of air in standard urologic procedures.

    Science.gov (United States)

    Ferretti, Stefania; Pasquarella, Cesira; Fornia, Samanta; Saccani, Elisa; Signorelli, Carlo; Vitali, Pietro; Sansebastiano, Giuliano Ezio

    2009-12-01

    Infection is one of the most feared complications of surgery. New instrumentation is being developed to reduce deposition of bacteria. We investigated 45 major surgical procedures (21 radical nephrectomies [RN] and 24 radical retropubic prostatectomies [RRP]) in our urology department during 2007. In about one-half of the interventions, an ultraclean air flow mobile (UAF) unit was used. Bacterial sedimentation was evaluated by nitrocellulose membranes placed on the instrument tray and by settle plates positioned at four points in the operating room. In 27 operations, an additional membrane was located near the incision. Bacterial counts on the nitrocellulose membranes during RN were 230 colony-forming units (cfu)/m(2)/h with the UAF unit and 2,254 cfu/m(2)/h without the unit (p = 0.001). During RRP, the values were 288 cfu/m(2)/h and 3,126 cfu/m(2)/h respectively (p = 0.001). The membrane placed near the incision during RN showed a microbial count of 1,235 cfu/m(2)/h with the UAF unit and 5,093 cfu/m(2)/h without the unit (p = 0.002); during RRP, the values were 1,845 cfu/m(2)/h and 3,790 cfu/m(2)/h, respectively (difference not significant). Bacterial contamination detected by settle plates during RN showed a mean value of 2,273 cfu/m(2)/h when the UAF unit was used and 2,054 cfu/m(2)/h without the unit; during RRP, the values were 2,332 cfu/m(2)/h and 2,629 cfu/m(2)/h with and without the UAF unit, respectively (NS). No statistically significant differences were detected in the clinical data registered in patients operated on under standard conditions and while the UAF unit was functioning. The UAF appears able to reduce microbial contamination at the operating table, reaching a bacterial number obtained in ultraclean operating theatres.

  5. Human herpesvirus 6B inhibits cell proliferation by a p53-independent pathway

    DEFF Research Database (Denmark)

    Øster, Bodil; Kaspersen, M.D.; Kofod-Olsen, Emil

    2006-01-01

    BACKGROUND: Various forms of cellular stress can activate the tumour suppressor protein p53, an important regulator of cell cycle arrest, apoptosis, and cellular senescence. Cells infected by human herpesvirus 6B (HHV-6B) accumulate aberrant amounts of p53. OBJECTIVES: The aim of this study...

  6. Role of Molecular Weight on the Mechanical Device Properties of Organic Polymer Solar Cells

    KAUST Repository

    Bruner, Christopher; Dauskardt, Reinhold

    2014-01-01

    important implications for long-Term reliability, manufacturing, and future applications of electronic organic thin films. In this work, we show that the molecular weight rr-P3HT in organic solar cells can also significantly change the internal cohesion

  7. P2X7 receptor blockade protects against cisplatin-induced nephrotoxicity in mice by decreasing the activities of inflammasome components, oxidative stress and caspase-3

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuanyuan; Yuan, Fahuan; Cao, Xuejiao [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China); Zhai, Zhifang [Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Gang Huang [Department of Medical Genetics, Third Military Medical University, Chongqing 430038 (China); Du, Xiang; Wang, Yiqin; Zhang, Jingbo; Huang, Yunjian; Zhao, Jinghong [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China); Hou, Weiping, E-mail: hwp0518@aliyun.com [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China)

    2014-11-15

    Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. The purinergic 2X7 receptor (P2X7R) plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the expression of P2X7R in cisplatin-induced nephrotoxicity in C57BL/6 mice, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after P2X7R blockade in vivo using an antagonist A-438079. Moreover, we measured the changes of nod-like receptor family, pyrin domain containing proteins (NLRP3) inflammasome components, oxidative stress, and proapoptotic genes in renal tissues in cisplatin-induced nephrotoxicity after treatment with A-438079. We found that the expression of P2X7R was significantly upregulated in the renal tubular epithelial cells in cisplatin-induced nephrotoxicity compared with that of the normal control group. Furthermore, pretreatment with A-438079 markedly attenuated the cisplatin-induced renal injury while lightening the histological damage, inflammatory response and apoptosis in renal tissue, and improved the renal function. These effects were associated with the significantly reduced levels of NLRP3 inflammasome components, oxidative stress, p53 and caspase-3 in renal tissues in cisplatin-induced nephrotoxicity. In conclusions, our studies suggest that the upregulated activity of P2X7R might play important roles in the development of cisplatin-induced nephrotoxicity, and P2X7R blockade might become an effective therapeutic strategy for this disease. - Highlights: • The P2X7R expression was markedly upregulated in cisplatin-induced nephrotoxicity. • P2X7R blockade significantly attenuated the cisplatin-induced renal injury. • P2X7R blockade reduced activities of NLRP3 inflammasome components in renal tissue. • P2X7R blockade

  8. Characteristic chemical components of the essential oil from white kwao krua (Pueraria mirifica).

    Science.gov (United States)

    Yagi, Nobuo; Nakahashi, Hiroshi; Kobayashi, Tomohiro; Miyazawa, Mitsuo

    2013-01-01

    The components of the essential oil from the roots of Pueraria mirifica were analyzed by capillary gas chromatography-mass spectrometry (GC-MS). Eighty-two components, representing 88.5% of the total oil, were identified by GC-MS. The main component of the oil was 2-pentylfuran, followed by hexanal and hexadecanol. With regard to the odor components from the essential oil of P. mirifica as determined by gas chromatography-olfactometry and aroma extract dilution analysis, it was revealed that phenylacetaldehyde and (2E)-nonenal imparted the green odor of the oil, and geraniol contributed to the sweet odor.

  9. E3 Ubiquitin Ligase RNF125 Activates Interleukin-36 Receptor Signaling and Contributes to Its Turnover.

    Science.gov (United States)

    Saha, Siddhartha S; Caviness, Gary; Yi, Guanghui; Raymond, Ernest L; Mbow, M Lamine; Kao, C Cheng

    2018-01-01

    Signaling by the interleukin-36 receptor (IL-36R) is linked to inflammatory diseases such as psoriasis. However, the regulation of IL-36R signaling is poorly understood. Activation of IL-36R signaling in cultured cells results in an increased polyubiquitination of the receptor subunit, IL-1Rrp2. Treatment with deubiquitinases shows that the receptor subunit of IL-36R, IL-1Rrp2, is primarily polyubiquitinated at the K63 position, which is associated with endocytic trafficking and signal transduction. A minor amount of ubiquitination is at the K48 position that is associated with protein degradation. A focused siRNA screen identified RNF125, an E3 ubiquitin ligase, to ubiquitinate IL-1Rrp2 upon activation of IL-36R signaling while not affecting the activated IL-1 receptor. Knockdown of RNF125 decreases signal transduction by the IL-36R. Overexpression of RNF125 in HEK293T cells activates IL-36R signaling and increases the ubiquitination of IL-1Rrp2 and its subsequent turnover. RNF125 can coimmunoprecipitate with the IL-36R, and it traffics with IL-1Rrp2 from the cell surface to lysosomes. Mutations of Lys568 and Lys569 in the C-terminal tail of IL-1Rrp2 decrease ubiquitination by RNF125 and increase the steady-state levels of IL-1Rrp2. These results demonstrate that RNF125 has multiple regulatory roles in the signaling, trafficking, and turnover of the IL-36R. © 2017 S. Karger AG, Basel.

  10. Ultrasensitive prostate specific antigen assay following laparoscopic radical prostatectomy--an outcome measure for defining the learning curve.

    Science.gov (United States)

    Viney, R; Gommersall, L; Zeif, J; Hayne, D; Shah, Z H; Doherty, A

    2009-07-01

    Radical retropubic prostatectomy (RRP) performed laparoscopically is a popular treatment with curative intent for organ-confined prostate cancer. After surgery, prostate specific antigen (PSA) levels drop to low levels which can be measured with ultrasensitive assays. This has been described in the literature for open RRP but not for laparoscopic RRP. This paper describes PSA changes in the first 300 consecutive patients undergoing non-robotic laparoscopic RRP by a single surgeon. To use ultrasensitive PSA (uPSA) assays to measure a PSA nadir in patients having laparoscopic radical prostatectomy below levels recorded by standard assays. The aim was to use uPSA nadir at 3 months' post-prostatectomy as an early surrogate end-point of oncological outcome. In so doing, laparoscopic oncological outcomes could then be compared with published results from other open radical prostatectomy series with similar end-points. Furthermore, this end-point could be used in the assessment of the surgeon's learning curve. Prospective, comprehensive, demographic, clinical, biochemical and operative data were collected from all patients undergoing non-robotic laparoscopic RRP. We present data from the first 300 consecutive patients undergoing laparoscopic RRP by a single surgeon. uPSA was measured every 3 months post surgery. Median follow-up was 29 months (minimum 3 months). The likelihood of reaching a uPSA of bench-marking performance. With experience, a surgeon can achieve in excess of an 80% chance of obtaining a uPSA nadir of < or = 0.01 ng/ml at 3 months after laparoscopic RRP for a British population. This is equivalent to most published open series.

  11. Revealing the Dimeric Crystal and Solution Structure of β-Lactoglobulin at pH 4 and Its pH and Salt Dependent Monomer–Dimer Equilibrium

    DEFF Research Database (Denmark)

    Khan, Sanaullah; Ipsen, Richard; Almdal, Kristoffer

    2018-01-01

    The dimeric structure of bovine β-lactoglobulin A (BLGA) at pH 4.0 was solved to 2.0 Å resolution. Fitting the BLGA pH 4.0 structure to SAXS data at low ionic strength (goodness of fit R-factor = 3.6%) verified the dimeric state in solution. Analysis of the monomer–dimer equilibrium at varying pH...... and ionic strength by SAXS and scattering modeling showed that BLGA is dimeric at pH 3.0 and 4.0, shifting toward a monomer at pH 2.2, 2.6, and 7.0 yielding monomer/dimer ratios of 80/20%, 50/50%, and 25/75%, respectively. BLGA remained a dimer at pH 3.0 and 4.0 in 50–150 mM NaCl, whereas the electrostatic...... shielding raised the dimer content at pH 2.2, 2.6, and 7.0, i.e., below and above the pI. Overall, the findings provide new insights into the molecular characteristics of BLGA relevant for dairy product formulations and for various biotechnological and pharmaceutical applications....

  12. One step beyond the electric dipole approximation: An experiment to observe the 5p6p forbidden transition in atomic rubidium

    Science.gov (United States)

    Ponciano-Ojeda, F.; Hernández-Gómez, S.; Mojica-Casique, C.; Ruiz-Martínez, E.; López-Hernández, O.; Colín-Rodríguez, R.; Ramírez-Martínez, F.; Flores-Mijangos, J.; Sahagún, D.; Jáuregui, R.; Jiménez-Mier, J.

    2018-01-01

    An advanced undergraduate experiment to study the 5 P 3 / 2 → 6 P 3 / 2 electric quadrupole transition in rubidium atoms is presented. The experiment uses two external cavity diode lasers, one operating at the D2 rubidium resonance line and the other built with commercial parts to emit at 911 nm. The lasers produce the 5 s → 5 p6 p excitation sequence in which the second step is the forbidden transition. Production of atoms in the 6 P 3 / 2 state is observed by detection of the 420 nm fluorescence that results from electric dipole decay into the ground state. Lines whose widths are significantly narrower than the Doppler width are used to study the hyperfine structure of the 6 P 3 / 2 state in rubidium. The spectra illustrate characteristics unique to electric dipole forbidden transitions, like the electric quadrupole selection rules; they are also used to show general aspects of two-color laser spectroscopy such as velocity selection and hyperfine pumping.

  13. Hydrogen-deuterium exchange and mass spectrometry reveal the pH-dependent conformational changes of diphtheria toxin T domain.

    Science.gov (United States)

    Li, Jing; Rodnin, Mykola V; Ladokhin, Alexey S; Gross, Michael L

    2014-11-04

    The translocation (T) domain of diphtheria toxin plays a critical role in moving the catalytic domain across the endosomal membrane. Translocation/insertion is triggered by a decrease in pH in the endosome where conformational changes of T domain occur through several kinetic intermediates to yield a final trans-membrane form. High-resolution structural studies are only applicable to the static T-domain structure at physiological pH, and studies of the T-domain translocation pathway are hindered by the simultaneous presence of multiple conformations. Here, we report the application of hydrogen-deuterium exchange mass spectrometry (HDX-MS) for the study of the pH-dependent conformational changes of the T domain in solution. Effects of pH on intrinsic HDX rates were deconvolved by converting the on-exchange times at low pH into times under our "standard condition" (pH 7.5). pH-Dependent HDX kinetic analysis of T domain clearly reveals the conformational transition from the native state (W-state) to a membrane-competent state (W(+)-state). The initial transition occurs at pH 6 and includes the destabilization of N-terminal helices accompanied by the separation between N- and C-terminal segments. The structural rearrangements accompanying the formation of the membrane-competent state expose a hydrophobic hairpin (TH8-9) to solvent, prepare it to insert into the membrane. At pH 5.5, the transition is complete, and the protein further unfolds, resulting in the exposure of its C-terminal hydrophobic TH8-9, leading to subsequent aggregation in the absence of membranes. This solution-based study complements high resolution crystal structures and provides a detailed understanding of the pH-dependent structural rearrangement and acid-induced oligomerization of T domain.

  14. Hydrogen–Deuterium Exchange and Mass Spectrometry Reveal the pH-Dependent Conformational Changes of Diphtheria Toxin T Domain

    Science.gov (United States)

    2015-01-01

    The translocation (T) domain of diphtheria toxin plays a critical role in moving the catalytic domain across the endosomal membrane. Translocation/insertion is triggered by a decrease in pH in the endosome where conformational changes of T domain occur through several kinetic intermediates to yield a final trans-membrane form. High-resolution structural studies are only applicable to the static T-domain structure at physiological pH, and studies of the T-domain translocation pathway are hindered by the simultaneous presence of multiple conformations. Here, we report the application of hydrogen–deuterium exchange mass spectrometry (HDX-MS) for the study of the pH-dependent conformational changes of the T domain in solution. Effects of pH on intrinsic HDX rates were deconvolved by converting the on-exchange times at low pH into times under our “standard condition” (pH 7.5). pH-Dependent HDX kinetic analysis of T domain clearly reveals the conformational transition from the native state (W-state) to a membrane-competent state (W+-state). The initial transition occurs at pH 6 and includes the destabilization of N-terminal helices accompanied by the separation between N- and C-terminal segments. The structural rearrangements accompanying the formation of the membrane-competent state expose a hydrophobic hairpin (TH8–9) to solvent, prepare it to insert into the membrane. At pH 5.5, the transition is complete, and the protein further unfolds, resulting in the exposure of its C-terminal hydrophobic TH8–9, leading to subsequent aggregation in the absence of membranes. This solution-based study complements high resolution crystal structures and provides a detailed understanding of the pH-dependent structural rearrangement and acid-induced oligomerization of T domain. PMID:25290210

  15. A Unique Failure Mechanism in the Nexus 6P Lithium-Ion Battery

    OpenAIRE

    Saurabh Saxena; Yinjiao Xing; Michael Pecht

    2018-01-01

    Nexus 6P smartphones have been beset by battery drain issues, which have been causing premature shutdown of the phone even when the charge indicator displays a significant remaining runtime. To investigate the premature battery drain issue, two Nexus 6P smartphones (one new and one used) were disassembled and their batteries were evaluated using computerized tomography (CT) scan analysis, electrical performance (capacity, resistance, and impedance) tests, and cycle life capacity fade tests. T...

  16. A reappraisal of the role of vesicourethral anastomosis biopsy in patient candidates for salvage radiation therapy after radical prostatectomy

    International Nuclear Information System (INIS)

    Roscigno, Marco; Cozzarini, Cesare; Scattoni, Vincenzo; Bertini, Roberto; Da Pozzo, Luigi; Pasta, Alessandra; Montorsi, Francesco; Bolognesi, Angelo; Fiorino, Claudio; Colombo, Renzo; Fazio, Ferruccio; Rigatti, Patrizio

    2007-01-01

    Background and purpose: To investigate the usefulness of vesicourethral anastomotic biopsy (VUBx) in patients who are candidates for salvage radiotherapy (SalvRT) after radical prostatectomy (RRP). Material and methods: From 1992 to 2001, 98 patients with a PSA failure (PSAf) after RRP underwent SalvRT to the prostatic bed (median dose 70 Gy). In 50/98 patients the VUBx was positive, in 26 negative; 22 patients underwent SalvRT without a prior VUBx. The prognostic impact on biochemical disease-free survival (bNEDs) of histologic confirmation of the local failure was evaluated retrospectively. Results: In the 40 patients with pre-RT PSA ≤ 0.9 ng/mL, no additional prognostic information derived from the VUBx, while, for higher PSA values, a positive histology resulted as a covariate independently predictive of post-RT outcome (5-year bNEDs: 74% vs 42% in the 35 and 23 patients with a positive or negative/not performed VUBx, respectively, P = .03), together with pT, pre-RT PSA ≤1.5 ng/mL, and PSA doubling time. Conclusions: In case of PSAf after RRP, VUBx before SalvRT seems unnecessary for PSA ≤ 0.9 ng/mL. For higher values, a positive VUBx seems to always justify a SalvRT, which may not be recommendable, given the nonnegligible risk of an already micrometastatic disease, if the biopsy results are negative

  17. Human herpesvirus 6B induces phosphorylation of p53 in its regulatory domain by a CK2- and p38-independent pathway

    DEFF Research Database (Denmark)

    Øster, Bodil; Bundgaard, B; Hupp, T R

    2008-01-01

    Here, we demonstrate that human herpesvirus 6B (HHV-6B) infection upregulates the tumour suppressor p53 and induces phosphorylation of p53 at Ser392. Interestingly, phosphorylation at the equivalent site has previously been shown to correlate with p53 tumour suppression in murine models. Although...

  18. Degree of phase separation effects on the charge transfer properties of P3HT:Graphene nanocomposites

    International Nuclear Information System (INIS)

    Bkakri, R.; Kusmartseva, O.E.; Kusmartsev, F.V.; Song, M.; Bouazizi, A.

    2015-01-01

    Graphene layers were introduced into the matrix of regioregular poly (3-hexylthiophene-2, 5-diyl) (RR-P3HT) via solution processing in the perspective of the development of organic nanocomposites with high P3HT/Graphene interfaces areas for efficient charge transfer process. P3HT and graphene act as electrons donor and electrons acceptor materials, respectively. Spatial Fourier Transforms (FFT) and power spectral density (PSD) analysis of the AFM images show that the phase separation decreases with increasing the graphene weight ratio in the P3HT matrix. The Raman spectra of the P3HT:Graphene nanocomposites shows that the G-band of graphene shifts to low frequencies with progressive addition of graphene which proves that there is an interaction between the nanowires of P3HT and the graphene layers. We suggest that the shift of the G-band is due to electrons transfer from P3HT to graphene. The quenching of the photoluminescence (PL) intensity of P3HT with addition of graphene proves also that an electrons transfer process occurred at the P3HT/Graphene interfaces. - Highlights: • Graphene layers are elaborated from expandable graphite oxide. • The effects of the graphene doping level on the charge transfer process were studied. • The phase separation process decreases with increasing the graphene content in the P3HT matrix. • Quenching of the PL intensity is due to electrons transfer from P3HT to graphene

  19. Heterologous expression of Helicoverpa armigera cytochrome P450 CYP6B7 in Pichia pastoris and interactions of CYP6B7 with insecticides.

    Science.gov (United States)

    Zhao, Chunqing; Song, Genmiao; Duan, Hongxia; Tang, Tao; Wang, Chen; Qiu, Lihong

    2017-09-01

    Previous studies indicated that constitutive over-expression of cytochrome P450 CYP6B7 was involved in fenvalerate resistance in Helicoverpa armigera. In this study, the CYP6B7 gene from H. armigera (namely HaCYP6B7), was heterologously expressed in Pichia pastoris GS115. A vector pPICZA-HaCYP6B7 was constructed and transformed into P. pastoris GS115, the transformant of pPICZA-HaCYP6B7-GS115 was then cultured and induced by 1% (v/v) methanol and the heterologous expression of HaCYP6B7 protein in P. pastoris was confirmed by SDS-PAGE and western blot. Microsomes containing the expressed HaCYP6B7 showed activities against model substrate p-nitroanisole and 7-ethoxycoumarin, with p-nitroanisole O-demethylation (PNOD) and 7-ethoxycoumarin O-deethylation (ECOD) activities of 15.66- and 4.75-fold of the control, respectively. Moreover, it showed degradation activities against the insecticides bifenthrin, fenvalerate and chlorpyrifos, with clearance activities of 6.88-, 1.49- and 2.27-fold of the control, respectively. The interactions of HaCYP6B7 with insecticides were further confirmed by molecular docking in silico with binding scores of 5.450, 5.295 and 2.197 between putative HaCYP6B7 protein and bifenthrin, fenvalerate and chlorpyrifos, respectively. The results of present study provided more direct and important evidence on the role of HaCYP6B7 conferring pyrethroid resistance in H. armigera. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  20. Iodinated chlorin p6 copper complex induces anti-proliferative effect in oral cancer cells through elevation of intracellular reactive oxygen species.

    Science.gov (United States)

    Sarbadhikary, Paromita; Dube, Alok

    2017-11-01

    We investigated the anticancer chemotoxicity of previously reported iodinated chlorin p 6 copper complex (ICp 6 -Cu), a novel chlorophyll derivative in which copper is attached to the side chain carboxylate groups via coordination. Human oral carcinoma cells NT8e, 4451 and the non-cancerous keratinocyte HaCaT cells were treated with ICp 6 -Cu for 48 h in dark and cell viability, proliferation and morphological alterations were examined. ICp 6 -Cu showed pronounced cytotoxicity in cancer cells with IC 50 ∼40 μM, whereas, the viability of HaCaT cells was not affected. Cell proliferation assay revealed that ICp 6 -Cu at IC 50 concentration led to complete inhibition of cell proliferation in both the cell lines. Cell morphology studied by confocal microscopy showed absence of cell death via necrosis or apoptosis. Instead, the treated cells displayed distinct features of non-apoptotic death such as highly vacuolated cytoplasm, lysosomal membrane permeabilization and damage to cytoskeleton F-actin filaments. In addition, ICp 6 -Cu treatment led to time dependent increase in the intracellular level of reactive oxygen species (ROS) and the cytotoxicity of ICp 6 -Cu was significantly inhibited by pre-treatment of cells with antioxidants (glutathione and trolox). These findings revealed that ICp 6 -Cu is a potent chemotoxic agent which can induce cytotoxic effect in cancer cells through elevation of intracellular ROS. It is suggested that ICp 6 -Cu may provide tumor selective chemotoxicity by exploiting difference of redox environment in normal and cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Chapter A6. Section 6.4. pH

    Science.gov (United States)

    Wilde, Franceska D.; Busenberg, Eurybiades; Radtke, Dean B.

    2006-01-01

    Measurement of pH is critical to the understanding of the viability and vulnerability of environmental waters and is considered a master variable in determining the aqueous geochemistry of an aqueous system. pH is a measure that represents the hydrogen-ion concentration (activity) of a solution. This section of the National Field Manual (NFM) describes U.S. Geological Survey (USGS) guidance and protocols for measurement of pH in ground and surface waters.

  2. Oxidation reactivity of 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) by Compound I model of cytochrome P450s

    Institute of Scientific and Technical Information of China (English)

    Zhongyu Wang; Zhiqiang Fu; Qi Yu; Jingwen Chen

    2017-01-01

    Alternative brominated flame retardants (BFRs) have become prevalent as a consequence of restrictions on the use of polybrominated diphenyl ethers (PBDEs).For risk assessment of these alternatives,knowledge of their metabolism via cytochrome P450 enzymes is needed.We have previously proved that density functional theory (DFT) is able to predict the metabolism of PBDEs by revealing the molecular mechanisms.In the current study,the reactivity of 1,2-bis(2,4,6-tribromophenoxy)ethane and structurally similar chemicals with the Compound I model representing the active site of P450 enzymes was investigated.The DFT calculations delineated reaction pathways which lead to reasonable explanations for products that were detected by wet experiments,meanwhile intermediates which cannot be determined were also proposed.Results showed that alkyl hydrogen abstraction will lead to bis(2,4,6-tribromophenoxy)ethanol,which may undergo hydrolysis yielding 2,4,6-tribromophenol,a neurotoxic compound.In addition,a general pattern of oxidation reactivity regarding the 2,4,6-tribromophenyl moiety was observed among several model compounds.Our study has provided insights for convenient evaluation of the metabolism of other structurally similar BFRs.

  3. The E7 protein of the cottontail rabbit papillomavirus immortalizes normal rabbit keratinocytes and reduces pRb levels, while E6 cooperates in immortalization but neither degrades p53 nor binds E6AP

    International Nuclear Information System (INIS)

    Ganzenmueller, Tina; Matthaei, Markus; Muench, Peter; Scheible, Michael; Iftner, Angelika; Hiller, Thomas; Leiprecht, Natalie; Probst, Sonja; Stubenrauch, Frank; Iftner, Thomas

    2008-01-01

    Human papillomaviruses (HPVs) cause cervical cancer and are associated with the development of non-melanoma skin cancer. A suitable animal model for papillomavirus-associated skin carcinogenesis is the infection of domestic rabbits with the cottontail rabbit papillomavirus (CRPV). As the immortalizing activity of CRPV genes in the natural target cells remains unknown, we investigated the properties of CRPV E6 and E7 in rabbit keratinocytes (RK) and their influence on the cell cycle. Interestingly, CRPV E7 immortalized RK after a cellular crisis but showed no such activity in human keratinocytes. Co-expressed CRPV E6 prevented cellular crisis. The HPV16 or CRPV E7 protein reduced rabbit pRb levels thereby causing rabbit p19 ARF induction and accumulation of p53 without affecting cellular proliferation. Both CRPV E6 proteins failed to degrade rabbit p53 in vitro or to bind E6AP; however, p53 was still inducible by mitomycin C. In summary, CRPV E7 immortalizes rabbit keratinocytes in a species-specific manner and E6 contributes to immortalization without directly affecting p53

  4. Induction of passive Heymann nephritis in complement component 6-deficient PVG rats.

    Science.gov (United States)

    Spicer, S Timothy; Tran, Giang T; Killingsworth, Murray C; Carter, Nicole; Power, David A; Paizis, Kathy; Boyd, Rochelle; Hodgkinson, Suzanne J; Hall, Bruce M

    2007-07-01

    Passive Heymann nephritis (PHN), a model of human membranous nephritis, is induced in susceptible rat strains by injection of heterologous antisera to rat renal tubular Ag extract. PHN is currently considered the archetypal complement-dependent form of nephritis, with the proteinuria resulting from sublytic glomerular epithelial cell injury induced by the complement membrane attack complex (MAC) of C5b-9. This study examined whether C6 and MAC are essential to the development of proteinuria in PHN by comparing the effect of injection of anti-Fx1A antisera into PVG rats deficient in C6 (PVG/C6(-)) and normal PVG rats (PVG/c). PVG/c and PVG/C6(-) rats developed similar levels of proteinuria at 3, 7, 14, and 28 days following injection of antisera. Isolated whole glomeruli showed similar deposition of rat Ig and C3 staining in PVG/c and PVG/C6(-) rats. C9 deposition was abundant in PVG/c but was not detected in PVG/C6(-) glomeruli, indicating C5b-9/MAC had not formed in PVG/C6(-) rats. There was also no difference in the glomerular cellular infiltrate of T cells and macrophages nor the size of glomerular basement membrane deposits measured on electron micrographs. To examine whether T cells effect injury, rats were depleted of CD8+ T cells which did not affect proteinuria in the early heterologous phase but prevented the increase in proteinuria associated with the later autologous phase. These studies showed proteinuria in PHN occurs without MAC and that other mechanisms, such as immune complex size, early complement components, CD4+ and CD8+ T cells, disrupt glomerular integrity and lead to proteinuria.

  5. Synthesis and luminescent properties of Sr{sub 2}Gd{sub 6.8}Eu{sub 1.2}Si{sub 6(1−x)}P{sub 6x}O{sub 26} oxyapatites

    Energy Technology Data Exchange (ETDEWEB)

    Ishchenko, A.V., E-mail: a-v-i@mail.ru [Ural Federal University, 620002 Ekaterinburg (Russian Federation); Zuev, M.G. [Ural Federal University, 620002 Ekaterinburg (Russian Federation); Institute of Solid State Chemistry, Ural Branch of the Russian Academy of Sciences, 620990 Ekaterinburg (Russian Federation); Vasin, A.A. [Institute of Solid State Chemistry, Ural Branch of the Russian Academy of Sciences, 620990 Ekaterinburg (Russian Federation); Yagodin, V.V.; Viktorov, L.V.; Shulgin, B.V. [Ural Federal University, 620002 Ekaterinburg (Russian Federation)

    2016-01-15

    The solid solutions Sr{sub 2}Gd{sub 6.8}Eu{sub 1.2}Si{sub 6(1−x)}P{sub 6x}O{sub 26−δ} (where x=0–0.15 and δ is oxygen nonstoichiometry) were synthesized. The structural properties of the crystal lattice of the solid solutions and the peculiarities of Eu{sup 3+} and P{sup 5+} dopants substitution for matrix ions have been considered. The photo-, X-ray and pulsed cathode luminescence properties have been studied. It has been found that substitution of (SiO{sub 4}){sup 4−} by (PO{sub 4}){sup 3−} tetrahedron in Eu{sup 3+}-doped oxyapatites does not bring significant changes to bands structure Eu{sup 3+} in luminescence spectra under different excitation (UV, X-ray, pulse cathode beam). However, the increase of P{sup 5+} concentration in Sr{sub 2}Gd{sub 6.8}Eu{sub 1.2}Si{sub 6(1−x)}P{sub 6x}O{sub 26–δ} compounds leads to a decrease of integral intensity of Eu{sup 3+} luminescence bands due to local environment symmetry modifications and covalency degree changes. Two nonequivalent optical Eu{sup 3+} centers have been found. These compounds are of interest for efficient X-ray phosphors, display devices and LED engineering material creation. - Highlights: • The luminescence properties were studied upon UV, X-ray and pulse cathode beam. • P{sup 5+} doping of Sr{sub 2}Gd{sub 6.8}Eu{sub 1.2}Si{sub 6}O{sub 26} leads to luminescence intensity reduction. • At least two types of optical centers formed by Eu{sup 3+} ions were found. • The structural features of Sr{sub 2}Gd{sub 6.8}Eu{sub 1.2}Si{sub 6(1−x)}P{sub 6x}O{sub 26} were reported. • Partial replacement of Si by P does not change the Sr{sub 2}Gd{sub 6.8}Eu{sub 1.2}Si{sub 6}O{sub 26} structure.

  6. Eukaryotic ribonucleases P/MRP: the crystal structure of the P3 domain.

    Science.gov (United States)

    Perederina, Anna; Esakova, Olga; Quan, Chao; Khanova, Elena; Krasilnikov, Andrey S

    2010-02-17

    Ribonuclease (RNase) P is a site-specific endoribonuclease found in all kingdoms of life. Typical RNase P consists of a catalytic RNA component and a protein moiety. In the eukaryotes, the RNase P lineage has split into two, giving rise to a closely related enzyme, RNase MRP, which has similar components but has evolved to have different specificities. The eukaryotic RNases P/MRP have acquired an essential helix-loop-helix protein-binding RNA domain P3 that has an important function in eukaryotic enzymes and distinguishes them from bacterial and archaeal RNases P. Here, we present a crystal structure of the P3 RNA domain from Saccharomyces cerevisiae RNase MRP in a complex with RNase P/MRP proteins Pop6 and Pop7 solved to 2.7 A. The structure suggests similar structural organization of the P3 RNA domains in RNases P/MRP and possible functions of the P3 domains and proteins bound to them in the stabilization of the holoenzymes' structures as well as in interactions with substrates. It provides the first insight into the structural organization of the eukaryotic enzymes of the RNase P/MRP family.

  7. Serial analysis of clinical and imaging indices reveals prolonged efficacy of TNF-α and IL-6 receptor targeted therapies in refractory Takayasu arteritis.

    Science.gov (United States)

    Youngstein, Taryn; Peters, James E; Hamdulay, Shahir S; Mewar, Devesh; Price-Forbes, Alec; Lloyd, Mark; Jeffery, Rachel; Kinderlerer, Anne R; Mason, Justin C

    2014-01-01

    We analysed a large cohort of patients with Takayasu arteritis, seeking robust clinical evidence for prolonged responses to tumour necrosis factor-α (TNF-α) and interleukin-6 receptor (IL-6R) antagonists in severe refractory disease. Case notes from ninety-eight patients with Takayasu arteritis were retrospectively reviewed. Drug treatment, laboratory and serial non-invasive imaging data were analysed, and the Indian Takayasu arteritis activity (ITAS) and damage scores (TADs) calculated. Nine patients were treated with biologic therapies. All had previously received high dose prednisolone and ≥1 conventional immunosuppressant. Five patients had failed cyclophosphamide. The patients prescribed biologics had more extensive arterial injury than the remainder of the cohort and persistent active disease (ITAS range 2-9, CRP 12-206 mg/L, TADs 3--1). Eight patients were prescribed anti-TNF-α therapy, three IL-6R blockade. The mean duration of anti-TNF-α treatment was 42 months (maximum 8 years). One patient developed new arterial stenoses while receiving anti-TNF-α and subsequently achieved disease remission with tocilizumab. Two patients have now demonstrated sustained responses to IL-6R inhibition at 19 and 20 months. Following introduction of biologic therapy, serial non-invasive imaging has revealed no significant progression in arterial injury. A significant fall in CRP (p<0.01), prednisolone dose (p<0.01) and ITAS (p<0.01) was observed, with no increase in TADs. We report for the first time sustained responses to both anti-TNF-α and IL6R antagonists in refractory Takayasu arteritis. As 5/9 patients were cyclophosphamide non-responders, we propose that biologics should now be considered ahead of cyclophosphamide in these young patients.

  8. Targeting Aberrant p70S6K Activation for Estrogen Receptor-Negative Breast Cancer Prevention.

    Science.gov (United States)

    Wang, Xiao; Yao, Jun; Wang, Jinyang; Zhang, Qingling; Brady, Samuel W; Arun, Banu; Seewaldt, Victoria L; Yu, Dihua

    2017-11-01

    The prevention of estrogen receptor-negative (ER-) breast cancer remains a major challenge in the cancer prevention field, although antiestrogen and aromatase inhibitors have shown adequate efficacy in preventing estrogen receptor-positive (ER + ) breast cancer. Lack of commonly expressed, druggable targets is a major obstacle for meeting this challenge. Previously, we detected the activation of Akt signaling pathway in atypical hyperplasic early-stage lesions of patients. In the current study, we found that Akt and the downstream 70 kDa ribosomal protein S6 kinase (p70S6K) signaling pathway was highly activated in ER - premalignant breast lesions and ER - breast cancer. In addition, p70S6K activation induced transformation of ER - human mammary epithelial cells (hMEC). Therefore, we explored the potential of targeting Akt/p70S6K in the p70S6K activated, ER - hMEC models and mouse mammary tumor models for the prevention of ER - breast cancer. We found that a clinically applicable Akt/p70S6K dual inhibitor, LY2780301, drastically decreased proliferation of hMECs with ErbB2-induced p70S6K activation via Cyclin B1 inhibition and cell-cycle blockade at G 0 -G 1 phase, while it did not significantly reverse the abnormal acinar morphology of these hMECs. In addition, a brief treatment of LY2780301 in MMTV- neu mice that developed atypical hyperplasia (ADH) and mammary intraepithelial neoplasia (MIN) lesions with activated p70S6K was sufficient to suppress S6 phosphorylation and decrease cell proliferation in hyperplasic MECs. In summary, targeting the aberrant Akt/p70S6K activation in ER - hMEC models in vitro and in the MMTV- neu transgenic mouse model in vivo effectively inhibited Akt/S6K signaling and reduced proliferation of hMECs in vitro and ADH/MIN lesions in vivo , indicating its potential in prevention of p70S6K activated ER - breast cancer. Cancer Prev Res; 10(11); 641-50. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Metabolite profile analysis reveals functional effects of 28-day vitamin B-6 restriction on one-carbon metabolism and tryptophan catabolic pathways in healthy men and women.

    Science.gov (United States)

    da Silva, Vanessa R; Rios-Avila, Luisa; Lamers, Yvonne; Ralat, Maria A; Midttun, Øivind; Quinlivan, Eoin P; Garrett, Timothy J; Coats, Bonnie; Shankar, Meena N; Percival, Susan S; Chi, Yueh-Yun; Muller, Keith E; Ueland, Per Magne; Stacpoole, Peter W; Gregory, Jesse F

    2013-11-01

    Suboptimal vitamin B-6 status, as reflected by low plasma pyridoxal 5'-phosphate (PLP) concentration, is associated with increased risk of vascular disease. PLP plays many roles, including in one-carbon metabolism for the acquisition and transfer of carbon units and in the transsulfuration pathway. PLP also serves as a coenzyme in the catabolism of tryptophan. We hypothesize that the pattern of these metabolites can provide information reflecting the functional impact of marginal vitamin B-6 deficiency. We report here the concentration of major constituents of one-carbon metabolic processes and the tryptophan catabolic pathway in plasma from 23 healthy men and women before and after a 28-d controlled dietary vitamin B-6 restriction (restriction yielded increased cystathionine (53% pre- and 76% postprandial; P restriction yielded lower kynurenic acid (22% pre- and 20% postprandial; P restriction and multilevel partial least squares-discriminant analysis supported this conclusion. Thus, plasma concentrations of creatine, cystathionine, kynurenic acid, and 3-hydroxykynurenine jointly reveal effects of vitamin B-6 restriction on the profiles of one-carbon and tryptophan metabolites and serve as biomarkers of functional effects of marginal vitamin B-6 deficiency.

  10. Case of 7p22.1 Microduplication Detected by Whole Genome Microarray (REVEAL in Workup of Child Diagnosed with Autism

    Directory of Open Access Journals (Sweden)

    Veronica Goitia

    2015-01-01

    Full Text Available Introduction. More than 60 cases of 7p22 duplications and deletions have been reported with over 16 of them occurring without concomitant chromosomal abnormalities. Patient and Methods. We report a 29-month-old male diagnosed with autism. Whole genome chromosome SNP microarray (REVEAL demonstrated a 1.3 Mb interstitial duplication of 7p22.1 ->p22.1 arr 7p22.1 (5,436,367–6,762,394, the second smallest interstitial 7p duplication reported to date. This interval included 14 OMIM annotated genes (FBXL18, ACTB, FSCN1, RNF216, OCM, EIF2AK1, AIMP2, PMS2, CYTH3, RAC1, DAGLB, KDELR2, GRID2IP, and ZNF12. Results. Our patient presented features similar to previously reported cases with 7p22 duplication, including brachycephaly, prominent ears, cryptorchidism, speech delay, poor eye contact, and outburst of aggressive behavior with autism-like features. Among the genes located in the duplicated segment, ACTB gene has been proposed as a candidate gene for the alteration of craniofacial development. Overexpression of RNF216L has been linked to autism. FSCN1 may play a role in neurodevelopmental disease. Conclusion. Characterization of a possible 7p22.1 Duplication Syndrome has yet to be made. Recognition of the clinical spectrum in patients with a smaller duplication of 7p should prove valuable for determining the minimal critical region, helping delineate a better prediction of outcome and genetic counseling

  11. Influence of the solution pH in the 6-mercaptopurine self-assembled monolayer (6MP-SAM) on a Au(111) single-crystal electrode.

    Science.gov (United States)

    Madueño, Rafael; García-Raya, Daniel; Viudez, Alfonso J; Sevilla, José M; Pineda, Teresa; Blázquez, Manuel

    2007-10-23

    Self-assembled monolayers (SAMs) of 6-mercaptopurine (6MP) have been prepared on a Au(111) single-crystal electrode by immersion of the metal surface in a 100 microM 6MP and 0.01 M HClO4 solution. The 6MP-SAM Au(111) single-crystal electrodes were transferred to the cell and allowed to equilibrate with the different aqueous working solutions before the electrochemical experiments. The influence of the solution pH was studied by cyclic voltammetry, double layer capacitance curves, and electrochemical impedance spectroscopy. The electrochemical behavior of the 6MP-SAM in acetic acid at pH 4 presents important differences in comparison to that obtained in 0.1 M KOH solutions. Cyclic voltammograms for the reductive desorption process in acid medium are broad and show some features that can be explained by a phase transition between a chemisorbed and a physisorbed state of the 6MP molecules. The low solubility of these molecules in acid medium could explain this phenomenon and the readsorption of the complete monolayer when the potential is scanned in the positive direction. The variation of the double-layer capacitance values in the potential range of monolayer stability with the pH suggests that the acid-base chemistry of the 6MP molecules is playing a role. This fact has been studied by following the variations of the electron-transfer rate constant of the highly charged redox probes as are Fe(CN)(6)-3/-4 and Ru(NH3)(6)+3/+2 as a function of solution pH. The apparent surface pKa value for the 6MP-SAM (pKa approximately 8) is explained by the total conversion of the different 6MP tautomers that exist in solution to the thiol species in the adsorbed state.

  12. Surgery-related complications in 1253 robot-assisted and 485 open retropubic radical prostatectomies at the Karolinska University Hospital, Sweden.

    Science.gov (United States)

    Carlsson, Stefan; Nilsson, Andreas E; Schumacher, Martin C; Jonsson, Martin N; Volz, Daniela S; Steineck, Gunnar; Wiklund, Peter N

    2010-05-01

    To quantify complications to surgery in patients treated with robot-assisted radical prostatectomy (RARP) and open retropubic radical prostatectomy (RRP) at our institution. Radical prostatectomy is associated with specific complications that can affect outcome results in patients. Between January 2002 and August 2007, a series of 1738 consecutive patients underwent RARP (n = 1253) or RRP (n = 485) for clinically localized prostate cancer. Surgery-related complications were assessed using a prospective hospital-based complication registry. The baseline characteristics of all patients were documented preoperatively. Overall, 170 patients required blood transfusions (9.7%), 112 patients (23%) in the RRP group compared with 58 patients (4.8%) in the RARP group. Infectious complications occurred in 44 RRP patients (9%) compared with 18 (1%) in the RARP group. Bladder neck contracture was treated in 22 (4.5%) patients who had undergone RRP compared with 3 (0.2%) in the RARP group. Clavien grade IIIb-V complications were more common in RRP patients (n = 63; 12.9%) than in RARP patients (n = 46; 3.7%). The introduction of RARP at our institution has resulted in decreased number of patients with Clavien grade IIIb-V complications, such as bladder neck contractures, a decrease in the number of patients who require blood transfusions, and decreased numbers of patients with postoperative wound infections. Copyright 2010 Elsevier Inc. All rights reserved.

  13. P-wave Feshbach resonances of ultracold 6Li

    International Nuclear Information System (INIS)

    Zhang, J.; Kempen, E.G.M. van; Bourdel, T.; Cubizolles, J.; Chevy, F.; Teichmann, M.; Tarruell, L.; Salomon, C.; Khaykovich, L.; Kokkelmans, S.J.J.M.F.

    2004-01-01

    We report the observation of three p-wave Feshbach resonances of 6 Li atoms in the lowest hyperfine state f=1/2. The positions of the resonances are in good agreement with theory. We study the lifetime of the cloud in the vicinity of the Feshbach resonances and show that, depending on the spin states, two- or three-body mechanisms are at play. In the case of dipolar losses, we observe a nontrivial temperature dependence that is well explained by a simple model

  14. Hinder för utomhusundervisning med fokus på årskurs 4-6

    OpenAIRE

    Petersson, Essi; Carstensen, Linnea

    2018-01-01

    I den här studien har vi tagit fram de hinder som begränsar möjligheterna för utomhusundervisning för elever i grundskolan, med fokus på årskurs 4-6 och middle school. Syftet med studien var att synliggöra vilka hinder som kan stå i vägen för utomhusundervisning samt visa på behov av vidare forskning i området. Forskningsfrågan som vi har försökt svara på är: Vad utgör hinder för utomhusundervisning med elever i grundskolan, med fokus på årskurs 4-6 och middle school? Studien bygger på den pr...

  15. Cauliflower mosaic virus protein P6 inhibits signaling responses to salicylic acid and regulates innate immunity.

    Directory of Open Access Journals (Sweden)

    Andrew J Love

    Full Text Available Cauliflower mosaic virus (CaMV encodes a multifunctional protein P6 that is required for translation of the 35S RNA and also acts as a suppressor of RNA silencing. Here we demonstrate that P6 additionally acts as a pathogenicity effector of an unique and novel type, modifying NPR1 (a key regulator of salicylic acid (SA- and jasmonic acid (JA-dependent signaling and inhibiting SA-dependent defence responses We find that that transgene-mediated expression of P6 in Arabidopsis and transient expression in Nicotiana benthamiana has profound effects on defence signaling, suppressing expression of representative SA-responsive genes and increasing expression of representative JA-responsive genes. Relative to wild-type Arabidopsis P6-expressing transgenics had greatly reduced expression of PR-1 following SA-treatment, infection by CaMV or inoculation with an avirulent bacterial pathogen Pseudomonas syringae pv tomato (Pst. Similarly transient expression in Nicotiana benthamiana of P6 (including a mutant form defective in translational transactivation activity suppressed PR-1a transcript accumulation in response to Agrobacterium infiltration and following SA-treatment. As well as suppressing the expression of representative SA-regulated genes, P6-transgenic Arabidopsis showed greatly enhanced susceptibility to both virulent and avirulent Pst (titres elevated 10 to 30-fold compared to non-transgenic controls but reduced susceptibility to the necrotrophic fungus Botrytis cinerea. Necrosis following SA-treatment or inoculation with avirulent Pst was reduced and delayed in P6-transgenics. NPR1 an important regulator of SA/JA crosstalk, was more highly expressed in the presence of P6 and introduction of the P6 transgene into a transgenic line expressing an NPR1:GFP fusion resulted in greatly increased fluorescence in nuclei even in the absence of SA. Thus in the presence of P6 an inactive form of NPR1 is mislocalized in the nucleus even in uninduced plants

  16. Observation of the Forbidden Magnetic Dipole Transition 6{sup 2}P{sub ½} --> 7{sup 2}P{sub ½} in Atomic Thallium

    Science.gov (United States)

    Chu, S.

    1976-10-01

    A measurement of the 6{sup 2}P{sub ½} --> 7{sup 2}P{sub ½} forbidden magnetic dipole matrix element in atomic thallium is described. A pulsed, linearly polarized dye laser tuned to the transition frequency is used to excite the thallium vapor from the 6{sup 2}P{sub ½} ground state to the 7{sup 2}P{sub ½} excited state. Interference between the magnetic dipole M1 amplitude and a static electric field induced E1 amplitude results in an atomic polarization of the 7{sup 2}P{sub ½} state, and the subsequent circular polarization of 535 nm fluorescence. The circular polarization is seen to be proportional to / as expected, and measured for several transitions between hyperfine levels of the 6{sup 2}P{sub ½} and 7{sup 2}P{sub ½} states. The result is = -(2.11 +- 0.30) x 10{sup -5} parallel bar e parallel bar dirac constant/2mc, in agreement with theory.

  17. Enzymatic Saccharification of Lignocelluloses Should be Conducted at Elevated pH 5.2-6.2

    Science.gov (United States)

    T.Q. Lan; Hongming Lou; J.Y. Zhu

    2013-01-01

    This study revealed that cellulose enzymatic saccharification response curves of lignocellulosic substrates were very different from those of pure cellulosic substrates in terms of optimal pH and pH operating window. The maximal enzymatic cellulose saccharification of lignocellulosic substrates occurs at substrate suspension

  18. Non-structural Components influencing Hospital Disaster Preparedness in Malaysia

    Science.gov (United States)

    Samsuddin, N. M.; Takim, R.; Nawawi, A. H.; Rosman, M. R.; SyedAlwee, S. N. A.

    2018-04-01

    Hospital disaster preparedness refers to measures taken by the hospital’s stakeholders to prepare, reduce the effects of disaster and ensure effective coordination during incident response. Among the measures, non-structural components (i.e., medical laboratory equipment & supplies; architectural; critical lifeline; external; updated building document; and equipment & furnishing) are critical towards hospital disaster preparedness. Nevertheless, over the past few years these components are badly affected due to various types of disasters. Hence, the objective of this paper is to investigate the non-structural components influencing hospital’s disaster preparedness. Cross-sectional survey was conducted among thirty-one (31) Malaysian hospital’s employees. A total of 6 main constructs with 107 non-structural components were analysed and ranked by using SPSS and Relative Importance Index (RII). The results revealed that 6 main constructs (i.e. medical laboratory equipment & supplies; architectural; critical lifeline; external; updated building document; and equipment & furnishing) are rated as ‘very critical’ by the respondents. Among others, availability of medical laboratory equipment and supplies for diagnostic and equipment was ranked first. The results could serve as indicators for the public hospitals to improve its disaster preparedness in terms of planning, organising, knowledge training, equipment, exercising, evaluating and corrective actions through non-structural components.

  19. BAG3 down-modulation sensitizes HPV18(+) HeLa cells to PEITC-induced apoptosis and restores p53.

    Science.gov (United States)

    Cotugno, Roberta; Basile, Anna; Romano, Elena; Gallotta, Dario; Belisario, Maria Antonietta

    2014-11-28

    BAG3 is a multi-functional component of tumor cell pro-survival machinery, and its biological functions have been largely associated to proteasome system. Here, we show that BAG3 down-modulation resulted in reduced cell viability and enhanced PEITC-induced apoptosis largely more extensively in HeLa (HPV18(+)) rather than in C33A (HPV(-)) cervical carcinoma cell lines. Moreover, we demonstrate that BAG3 suppression led to a decrease of viral E6 oncoprotein and a concomitant recovery of p53 tumor suppressor, the best recognized target of E6 for proteasome degradation. E6 and p53 expression were modulated at protein level, since their respective mRNAs were unaffected. Taken together our findings reveal a novel role for BAG3 as host protein contributing to HPV18 E6-activated pro-survival strategies, and suggest a possible relevance of its expression levels in drug/radiotherapy-resistance of HPV18-bearing cervical carcinomas. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Seismic tomography with P and S data reveals lateral variations in the rigidity of slabs

    NARCIS (Netherlands)

    Widiyantoro, S.; Kennett, B.L.N.; Hilst, R.D. van der

    1999-01-01

    Regional seismic tomography of the northwest Pacific island arcs using P- and S-wave arrival time data with similar path coverage reveals an oceanic lithospheric slab deflected in the mantle transition zone beneath the Izu Bonin region in good agreement with the results of earlier tomographic and

  1. Small supernumerary marker chromosome causing partial trisomy 6p in a child with craniosynostosis.

    Science.gov (United States)

    Villa, Olaya; Del Campo, Miguel; Salido, Marta; Gener, Blanca; Astier, Laura; Del Valle, Jesús; Gallastegui, Fátima; Pérez-Jurado, Luis A; Solé, Francesc

    2007-05-15

    We report on a child with a small supernumerary marker chromosome (sSMC) causing partial trisomy 6p. The child showed a phenotype consisting of neonatal craniosynostosis, microcephaly, and borderline developmental delay. By molecular techniques the sSMC has been shown to contain approximately 16 Mb of genomic DNA from 6p21.1 to 6cen, being de novo and of maternal origin.

  2. Proceedings of Japan-U.S. workshop P-196 on high heat flux components and plasma surface interactions for next devices

    International Nuclear Information System (INIS)

    Wilson, K.N.; Yamashina, T.

    1993-03-01

    The Japan-US Workshop P-196 was successfully carried out in Kyushu University, Chikushi Campus, from November 17 to 19. The major concern was on the research and development required both for international Thermonuclear Experimental Reactor (ITER) and Large Helical Device (LHD). Most of the discussion items was similar to that of the last workshop, e.g. PFC and PSI in Large Device, High Heat Flux Component, Laboratory Studies and Neutron Damage. The presentation number concerning High Heat Flux Component was largest. (J.P.N.)

  3. Mixed infection of Sida jamaicensis in Jamaica reveals the presence of three recombinant begomovirus DNA A components.

    Science.gov (United States)

    Stewart, Cheryl; Kon, Tatsuya; Rojas, Maria; Graham, André; Martin, Darren; Gilbertson, Robert; Roye, Marcia

    2014-09-01

    Begomoviruses impose serious constraints on agriculture throughout the temperate, tropical and subtropical regions. Previously, we characterised a sida golden yellow vein virus isolate, SiGYVV-[JM:Lig2:08] (HQ009519-20) from a symptomatic Sida jamaicensis plant. With the aim of establishing whether it was hosting a mixed infection that could facilitate recombination, PCR-RFLP was done on DNA extracted from this plant, and the results suggested the presence of two additional genetically distinct DNA-A molecules. Sequence analysis of these two DNA-A molecules (relying on BLAST searches and the CLUSTAL V algorithm within the DNASTAR MegAlign module) revealed that they belonged to novel species, and we have tentatively named these viruses sida golden mosaic Braco virus-[Jamaica:Liguanea:2008] and sida golden mosaic Liguanea virus-[Jamaica:1:2008]. Using RDP4 (recombination detection program), we determined that all three viruses were recombinant, with bases ~10 to ~440 of both SiGMLigV-[JM:Lig:08] and SiGYVV-[JM:Lig2:08] having been derived from a relative of SiGMBV-[JM:Lig:08] (P<2.070×10(-7) for all seven of the recombination detection methods). SiGMBV-[JM:Lig:08] was itself a product of recombination, deriving bases ~490-1195 from a virus that was ~92% similar to malvastrum yellow mosaic Helshire virus. Phylogenetically, these DNA-A components are most closely related to those of malvaceous weed-infecting begomoviruses from Jamaica, Cuba, Florida and Mexico. The SiGMBV DNA-A was able to elicit symptomatic infection in N. benthamiana.

  4. Genome-wide mapping of Sox6 binding sites in skeletal muscle reveals both direct and indirect regulation of muscle terminal differentiation by Sox6

    Directory of Open Access Journals (Sweden)

    An Chung-Il

    2011-10-01

    Full Text Available Abstract Background Sox6 is a multi-faceted transcription factor involved in the terminal differentiation of many different cell types in vertebrates. It has been suggested that in mice as well as in zebrafish Sox6 plays a role in the terminal differentiation of skeletal muscle by suppressing transcription of slow fiber specific genes. In order to understand how Sox6 coordinately regulates the transcription of multiple fiber type specific genes during muscle development, we have performed ChIP-seq analyses to identify Sox6 target genes in mouse fetal myotubes and generated muscle-specific Sox6 knockout (KO mice to determine the Sox6 null muscle phenotype in adult mice. Results We have identified 1,066 Sox6 binding sites using mouse fetal myotubes. The Sox6 binding sites were found to be associated with slow fiber-specific, cardiac, and embryonic isoform genes that are expressed in the sarcomere as well as transcription factor genes known to play roles in muscle development. The concurrently performed RNA polymerase II (Pol II ChIP-seq analysis revealed that 84% of the Sox6 peak-associated genes exhibited little to no binding of Pol II, suggesting that the majority of the Sox6 target genes are transcriptionally inactive. These results indicate that Sox6 directly regulates terminal differentiation of muscle by affecting the expression of sarcomere protein genes as well as indirectly through influencing the expression of transcription factors relevant to muscle development. Gene expression profiling of Sox6 KO skeletal and cardiac muscle revealed a significant increase in the expression of the genes associated with Sox6 binding. In the absence of the Sox6 gene, there was dramatic upregulation of slow fiber-specific, cardiac, and embryonic isoform gene expression in Sox6 KO skeletal muscle and fetal isoform gene expression in Sox6 KO cardiac muscle, thus confirming the role Sox6 plays as a transcriptional suppressor in muscle development

  5. Integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

    Energy Technology Data Exchange (ETDEWEB)

    Sansing, Hope A. [Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center-New Orleans, School of Dentistry, New Orleans, LA (United States); Sarkeshik, Ali; Yates, John R. [Department of Chemical Physiology, Scripps Research Institute, La Jolla, CA (United States); Patel, Vyomesh; Gutkind, J. Silvio [Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Yamada, Kenneth M. [Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Berrier, Allison L., E-mail: allison.berrier@gmail.com [Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center-New Orleans, School of Dentistry, New Orleans, LA (United States)

    2011-03-11

    Research highlights: {yields} Proteomics of clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} receptors in oral carcinoma. {yields} p130Cas, Dek, Src and talin regulate oral carcinoma invasion. {yields} p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomics screen of proteins recruited to clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta} or {alpha}{sub 6}{beta} receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.

  6. Clustering by neurocognition for fine-mapping of the schizophrenia susceptibility loci on chromosome 6p

    Science.gov (United States)

    Lin, Sheng-Hsiang; Liu, Chih-Min; Liu, Yu-Li; Fann, Cathy Shen-Jang; Hsiao, Po-Chang; Wu, Jer-Yuarn; Hung, Shuen-Iu; Chen, Chun-Houh; Wu, Han-Ming; Jou, Yuh-Shan; Liu, Shi K.; Hwang, Tzung J.; Hsieh, Ming H.; Chang, Chien-Ching; Yang, Wei-Chih; Lin, Jin-Jia; Chou, Frank Huang-Chih; Faraone, Stephen V.; Tsuang, Ming T.; Hwu, Hai-Gwo; Chen, Wei J.

    2009-01-01

    Chromosome 6p is one of the most commonly implicated regions in the genome-wide linkage scans of schizophrenia, whereas further association studies for markers in this region were inconsistent likely due to heterogeneity. This study aimed to identify more homogeneous subgroups of families for fine mapping on regions around markers D6S296 and D6S309 (both in 6p24.3) as well as D6S274 (in 6p22.3) by means of similarity in neurocognitive functioning. A total of 160 families of patients with schizophrenia comprising at least two affected siblings who had data for 8 neurocognitive test variables of the Continuous Performance Test (CPT) and the Wisconsin Card Sorting Test (WCST) were subjected to cluster analysis with data visualization using the test scores of both affected siblings. Family clusters derived were then used separately in family-based association tests for 64 single nucleotide polymorphisms covering the region of 6p24.3 and 6p22.3. Three clusters were derived from the family-based clustering, with deficit cluster 1 representing deficit on the CPT, deficit cluster 2 representing deficit on both the CPT and the WCST, and a third cluster of non-deficit. After adjustment using false discovery rate for multiple testing, SNP rs13873 and haplotype rs1225934-rs13873 on BMP6-TXNDC5 genes were significantly associated with schizophrenia for the deficit cluster 1 but not for the deficit cluster 2 or non-deficit cluster. Our results provide further evidence that the BMP6-TXNDC5 locus on 6p24.3 may play a role in the selective impairments on sustained attention of schizophrenia. PMID:19694819

  7. Continuous Ecosystem Stoichiometry (C:N:P) in a Large Spring-fed River Reveals Decoupled N and P Assimilatory Dynamics

    Science.gov (United States)

    Cohen, M. J.; Douglass, R. L.; Martin, J. B.; Thomas, R. G.; Heffernan, J. B.; Foster, C. R.

    2010-12-01

    Diel variation in solutes offers insight into lotic ecosystem processes. Diel variation in dissolved oxygen (DO) is the standard method to estimate aquatic primary production (C fixation). Recently, diel variation in nitrate concentration was used to infer rates and pathways of N processing. From coupled C and N measurements, stoichiometric ratios of nutrient assimilation can be obtained, and variation therein linked back to environmental drivers and ecological changes. Here we present data obtained using an in situ phosphate sensor (Cycle-P, WetLabs, Philomath OR) that permits coupled high frequency C, N and P measurements. We collected hourly samples over 3 two-week deployments in the Ichetucknee River, a large (Q ~ 10 m3 s-1), productive (GPP ~ 6 g C m-2 d-1), entirely spring-fed river in north Florida. We observed average soluble reactive P (SRP) concentrations of 44, 41 and 45 µg/L for Dec-09, Feb-10 and Apr-10, respectively, and marked diel variation that averaged 6.7±0.9 µg/L. Observed river concentrations were consistently at or below the flow-weighted average input concentration of the 6 main springs that feed the river (49 µg/L) suggesting net SRP removal over the 5 km reach. Removal from co-precipitation with calcite or Fe-oxides is unlikely since variation in Fe and Ca is smaller than, and out of phase with, P variation. Since internal stores are presumed to be at steady-state given conditions of constant discharge, the balance of P export likely occurs as organic matter. Based on discharge during each deployment, diel variation of P concentrations indicate system-wide assimilation of 1505 ± 423 g P d-1, or 8.0 ± 2.3 mg P m-2 d-1 over the 17 ha of benthic surface area. Contemporaneous measurements of DO and nitrate implied average ecosystem stoichiometry (C:N:P) of 267:14:1, consistent with production dominated by submerged aquatic macrophytes rather than algae and other microflora. Of particular interest is the observation that diel variation in

  8. Autozygosity mapping of a large consanguineous Pakistani family reveals a novel non-syndromic autosomal recessive mental retardation locus on 11p15-tel

    DEFF Research Database (Denmark)

    Rehman, Shoaib ur; Baig, Shahid Mahmood; Eiberg, Hans

    2011-01-01

    done in all sampled individuals in the family. The nuclear central loop in the five generation family showed homozygosity for a 6-Mb telomeric region on 11p15, whereas all other linkage regions were excluded by calculation of logarithm of odds (LOD) for the SNP microarray data. A maximum LOD score of Z......Autosomal recessive inherited mental retardation is an extremely heterogeneous disease and accounts for approximately 25% of all non-syndromic mental retardation cases. Autozygosity mapping of a large consanguineous Pakistani family revealed a novel locus for non-syndromic autosomal recessive...

  9. Nonsyndromic cleft lip and palate: Evidence of linkage to a microsatellite marker on 6p23

    Energy Technology Data Exchange (ETDEWEB)

    Carinci, F.; Pezzetti, F.; Scapoli, L.; Padula, E.; Baciliero, U.; Curioni, C.; Tognon, M.

    1995-01-01

    Nonsydromic cleft lip with or without secondary clefting of the palate (CL+/{minus}P) is one of the most common birth defects. A previous linkage study concerning CL+/{minus}P and cleft palate (CP) families indicated chromosome 6p, near F13A locus, as a possible region for the presence of a clefting gene. More recently, another linkage study performed on a sample of 12 families with nonsyndromic CL+/{minus}P seemed to exclude this association. To test the hypothesis on the possible presence of a major gene on chromosome 6p, we carried out a study on a large sample (21) of CL+/{minus}P families from northeastern Italy. In conclusion, our investigation can be summarized as follows: (i) CL+/{minus}P disease appears to be heterogeneous; (ii) {approximately}66% of the pedigrees showed an autosomal dominant inheritance with incomplete penetrance; and (iii) CL+/{minus}P locus maps on 6p23 very close to or at the microsatellite marker D6S89. To verify whether the D6S89 is the closest marker to the CL+/{minus}P locus, additional examinations with new markers are underway. 19 refs., 1 fig., 1 tab.

  10. The multielectron character of the S 2p → 4e{sub g} shape resonance in the SF{sub 6} molecule studied via detection of soft X-ray emission and neutral high-Rydberg fragments

    Energy Technology Data Exchange (ETDEWEB)

    Kivimäki, A., E-mail: kivimaki@iom.cnr.it [CNR—Istituto Officina dei Materiali (IOM), Laboratorio TASC, 34149 Trieste (Italy); Coreno, M. [CNR—Istituto di Struttura della Materia (ISM), Basovizza Area Science Park, 34149 Trieste (Italy); Miotti, P.; Frassetto, F.; Poletto, L. [CNR—Istituto di Fotonica e Nanotecnologie (IFN), via Trasea 7, 35131 Padova (Italy); Stråhlman, C. [MAX IV Laboratory, Lund University, P.O. Box 118, 22100 Lund (Sweden); Simone, M. de [CNR—Istituto Officina dei Materiali (IOM), Laboratorio TASC, 34149 Trieste (Italy); Richter, R. [Elettra-Sincrotrone Trieste, Area Science Park Basovizza, 34149 Trieste (Italy)

    2016-05-15

    Highlights: • The soft X-ray emission spectrum of SF{sub 6} changes at the S 2p → 4e{sub g} shape resonance. • The emission band around 172 eV indicates the population of the 6a{sub 1g} orbital. • Shake-up processes accompanying S 2p ionization can explain the new emissions. • Field ionization of neutral high Rydberg (HR) fragments reveals F and S atoms. • The yield of neutral HR fragments increases at the S 2p → 4e{sub g} shape resonance. - Abstract: We have studied the nature of the S 2p → 4e{sub g} shape resonance in the SF{sub 6} molecule by performing two different experiments. Soft X-ray emission spectra measured at the 4e{sub g} shape resonance reveal features that do not originate from the S 2p{sup −1} states. One of the features can be assigned to the 6a{sub 1g} → S 2p transition. The 6a{sub 1g} orbital, which is empty in the molecular ground state, can be populated either in core–valence double excitations or in S 2p shake-up transitions. Both these channels are considered. We have also studied the fragmentation of SF{sub 6} molecule after the decay of the S 2p core-hole states by observing neutral fragments in high-Rydberg states, where an electron occupies an orbital with n ≥ 20 (n is the principal quantum number). Such neutral fragments become, in relative terms, more abundant at the S 2p → 4e{sub g} shape resonance with respect to the S 2p → 2t{sub 2g} shape resonance, which is a pure one-electron phenomenon.

  11. Transcript specificity in yeast pre-mRNA splicing revealed by mutations in core spliceosomal components.

    Directory of Open Access Journals (Sweden)

    Jeffrey A Pleiss

    2007-04-01

    Full Text Available Appropriate expression of most eukaryotic genes requires the removal of introns from their pre-messenger RNAs (pre-mRNAs, a process catalyzed by the spliceosome. In higher eukaryotes a large family of auxiliary factors known as SR proteins can improve the splicing efficiency of transcripts containing suboptimal splice sites by interacting with distinct sequences present in those pre-mRNAs. The yeast Saccharomyces cerevisiae lacks functional equivalents of most of these factors; thus, it has been unclear whether the spliceosome could effectively distinguish among transcripts. To address this question, we have used a microarray-based approach to examine the effects of mutations in 18 highly conserved core components of the spliceosomal machinery. The kinetic profiles reveal clear differences in the splicing defects of particular pre-mRNA substrates. Most notably, the behaviors of ribosomal protein gene transcripts are generally distinct from other intron-containing transcripts in response to several spliceosomal mutations. However, dramatically different behaviors can be seen for some pairs of transcripts encoding ribosomal protein gene paralogs, suggesting that the spliceosome can readily distinguish between otherwise highly similar pre-mRNAs. The ability of the spliceosome to distinguish among its different substrates may therefore offer an important opportunity for yeast to regulate gene expression in a transcript-dependent fashion. Given the high level of conservation of core spliceosomal components across eukaryotes, we expect that these results will significantly impact our understanding of how regulated splicing is controlled in higher eukaryotes as well.

  12. Principal Component Analysis of Working Memory Variables during Child and Adolescent Development.

    Science.gov (United States)

    Barriga-Paulino, Catarina I; Rodríguez-Martínez, Elena I; Rojas-Benjumea, María Ángeles; Gómez, Carlos M

    2016-10-03

    Correlation and Principal Component Analysis (PCA) of behavioral measures from two experimental tasks (Delayed Match-to-Sample and Oddball), and standard scores from a neuropsychological test battery (Working Memory Test Battery for Children) was performed on data from participants between 6-18 years old. The correlation analysis (p 1), the scores of the first extracted component were significantly correlated (p < .05) to most behavioral measures, suggesting some commonalities of the processes of age-related changes in the measured variables. The results suggest that this first component would be related to age but also to individual differences during the cognitive maturation process across childhood and adolescence stages. The fourth component would represent the speed-accuracy trade-off phenomenon as it presents loading components with different signs for reaction times and errors.

  13. The P450 CYP6Z1 confers carbamate/pyrethroid cross-resistance in a major African malaria vector beside a novel carbamate-insensitive N485I acetylcholinesterase-1 mutation.

    Science.gov (United States)

    Ibrahim, Sulaiman S; Ndula, Miranda; Riveron, Jacob M; Irving, Helen; Wondji, Charles S

    2016-07-01

    Carbamates are increasingly used for vector control notably in areas with pyrethroid resistance. However, a cross-resistance between these insecticides in major malaria vectors such as Anopheles funestus could severely limit available resistance management options. Unfortunately, the molecular basis of such cross-resistance remains uncharacterized in An. funestus, preventing effective resistance management. Here, using a genomewide transcription profiling, we revealed that metabolic resistance through upregulation of cytochrome P450 genes is driving carbamate resistance. The P450s CYP6P9a, CYP6P9b and CYP6Z1 were the most upregulated detoxification genes in the multiple resistant mosquitoes. However, in silico docking simulations predicted CYP6Z1 to metabolize both pyrethroids and carbamates, whereas CYP6P9a and CYP6P9b were predicted to metabolize only the pyrethroids. Using recombinant enzyme metabolism and inhibition assays, we demonstrated that CYP6Z1 metabolizes bendiocarb and pyrethroids, whereas CYP6P9a and CYP6P9b metabolize only the pyrethroids. Other upregulated gene families in resistant mosquitoes included several cuticular protein genes suggesting a possible reduced penetration resistance mechanism. Investigation of the target-site resistance in acetylcholinesterase 1 (ace-1) gene detected and established the association between the new N485I mutation and bendiocarb resistance (odds ratio 7.3; P resistance and improve the design of effective resistance management strategies to control this malaria vector. © 2016 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

  14. Bi–Mn mixed metal organic oxide: A novel 3d-6p mixed metal coordination network

    International Nuclear Information System (INIS)

    Shi, Fa-Nian; Rosa Silva, Ana; Bian, Liang

    2015-01-01

    A new terminology of metal organic oxide (MOO) was given a definition as a type of coordination polymers which possess the feature of inorganic connectivity between metals and the direct bonded atoms and show 1D, 2D or 3D inorganic sub-networks. One such compound was shown as an example. A 3d-6p (Mn–Bi. Named MOOMnBi) mixed metals coordination network has been synthesized via hydrothermal method. The new compound with the molecular formula of [MnBi 2 O(1,3,5-BTC) 2 ] n (1,3,5-BTC stands for benzene-1,3,5-tricarboxylate) was characterized via single crystal X-ray diffraction technique that revealed a very interesting 3-dimensional (3D) framework with Bi 4 O 2 (COO) 12 clusters which are further connected to Mn(COO) 6 fragments into a 2D MOO. The topology study indicates an unprecedented topological type with the net point group of (4 13 .6 2 )(4 13 .6 8 )(4 16 .6 5 )(4 18 .6 10 )(4 22 .6 14 )(4 3 ) corresponding to 3,6,7,7,8,9-c hexa-nodal net. MOOMnBi shows catalytic activity in the synthesis of (E)-α,β-unsaturated ketones. - Graphical abstract: This metal organic framework (MOF) is the essence of a 2D metal organic oxide (MOO). - Highlights: • New concept of metal organic oxide (MOO) was defined and made difference from metal organic framework. • New MOO of MOOMnBi was synthesized by hydrothermal method. • Crystal structure of MOOMnBi was determined by single crystal X-ray analysis. • The catalytic activity of MOOMnBi was studied showing reusable after 2 cycles

  15. Structure and Mechanism of the S Component of a Bacterial ECF Transporter

    Energy Technology Data Exchange (ETDEWEB)

    P Zhang; J Wang; Y Shi

    2011-12-31

    The energy-coupling factor (ECF) transporters, responsible for vitamin uptake in prokaryotes, are a unique family of membrane transporters. Each ECF transporter contains a membrane-embedded, substrate-binding protein (known as the S component), an energy-coupling module that comprises two ATP-binding proteins (known as the A and A' components) and a transmembrane protein (known as the T component). The structure and transport mechanism of the ECF family remain unknown. Here we report the crystal structure of RibU, the S component of the ECF-type riboflavin transporter from Staphylococcus aureus at 3.6-{angstrom} resolution. RibU contains six transmembrane segments, adopts a previously unreported transporter fold and contains a riboflavin molecule bound to the L1 loop and the periplasmic portion of transmembrane segments 4-6. Structural analysis reveals the essential ligand-binding residues, identifies the putative transport path and, with sequence alignment, uncovers conserved structural features and suggests potential mechanisms of action among the ECF transporters.

  16. T20 measurements for 1H(d searrow,γ)3He and the P-wave component of the nucleon-nucleon force

    International Nuclear Information System (INIS)

    Schmid, G.J.; Chasteler, R.M.; Weller, H.R.; Tilley, D.R.; Fonseca, A.C.; Lehman, D.R.

    1996-01-01

    Measurements of T 20 (θ lab =90 degree) for 1 H(d searrow,γ) 3 He, in the energy range E d (lab)=12.7 endash 19.8 MeV, have been compared with the results of new exact three-body Faddeev calculations using the Paris and Bonn-A nucleon-nucleon (NN) potentials. This comparison indicates a strong sensitivity of the T 20 observable to the p-wave part of the NN force. In particular, we find that the 3 P 1 component of the P-wave interaction is the dominant P-wave term affecting the value of T 20 (θ lab =90 degree) at these energies. This contrasts with the results of polarized N-D scattering studies where the 3 P 0 component has been found to dominate. cents 1996 The American Physical Society

  17. Recurrent Respiratory Papillomatosis or Laryngeal Papillomatosis

    Science.gov (United States)

    ... Home » Health Info » Voice, Speech, and Language Recurrent Respiratory Papillomatosis or Laryngeal Papillomatosis On this page: What ... find additional information about RRP? What is recurrent respiratory papillomatosis? Recurrent respiratory papillomatosis (RRP) is a disease ...

  18. Metabolite Profile Analysis Reveals Functional Effects of 28-Day Vitamin B-6 Restriction on One-Carbon Metabolism and Tryptophan Catabolic Pathways in Healthy Men and Women123

    Science.gov (United States)

    da Silva, Vanessa R.; Rios-Avila, Luisa; Lamers, Yvonne; Ralat, Maria A.; Midttun, Øivind; Quinlivan, Eoin P.; Garrett, Timothy J.; Coats, Bonnie; Shankar, Meena N.; Percival, Susan S.; Chi, Yueh-Yun; Muller, Keith E.; Ueland, Per Magne; Stacpoole, Peter W.; Gregory, Jesse F.

    2013-01-01

    Suboptimal vitamin B-6 status, as reflected by low plasma pyridoxal 5′-phosphate (PLP) concentration, is associated with increased risk of vascular disease. PLP plays many roles, including in one-carbon metabolism for the acquisition and transfer of carbon units and in the transsulfuration pathway. PLP also serves as a coenzyme in the catabolism of tryptophan. We hypothesize that the pattern of these metabolites can provide information reflecting the functional impact of marginal vitamin B-6 deficiency. We report here the concentration of major constituents of one-carbon metabolic processes and the tryptophan catabolic pathway in plasma from 23 healthy men and women before and after a 28-d controlled dietary vitamin B-6 restriction (restriction yielded increased cystathionine (53% pre- and 76% postprandial; P restriction yielded lower kynurenic acid (22% pre- and 20% postprandial; P restriction and multilevel partial least squares-discriminant analysis supported this conclusion. Thus, plasma concentrations of creatine, cystathionine, kynurenic acid, and 3-hydroxykynurenine jointly reveal effects of vitamin B-6 restriction on the profiles of one-carbon and tryptophan metabolites and serve as biomarkers of functional effects of marginal vitamin B-6 deficiency. PMID:23966327

  19. Increased plasma concentration of serum amyloid P component in centenarians with impaired cognitive performance

    DEFF Research Database (Denmark)

    Nybo, M; Olsen, H; Jeune, B

    1998-01-01

    these to the cognitive performance evaluated by Mini Mental State Examination (MMSE). We observed a significantly (p gender-matched controls (32.8+/-11.4 microg/ml). Six severely demented centenarians had an even......Serum amyloid P component (SAP) binds to all amyloid fibrils including those in the plaques and tangles of Alzheimer patients. To investigate whether the plasma SAP concentration correlated to cognitive impairment, we measured SAP levels in blood samples from 41 centenarians and compared...... higher SAP concentration (60.2 microg/ml), while the subgroup of cognitive intact centenarians (MMSE score >24) showed a normal SAP concentration (38.4+/-9.3 microg/ml). No dehydration or hepatic dysfunction was demonstrable in the centenarians. We conclude that the centenarians with impaired cognitive...

  20. Genetic diversity of Plasmodium Vivax revealed by the merozoite surface protein-1 icb5-6 fragment.

    Science.gov (United States)

    Ruan, Wei; Zhang, Ling-Ling; Feng, Yan; Zhang, Xuan; Chen, Hua-Liang; Lu, Qiao-Yi; Yao, Li-Nong; Hu, Wei

    2017-06-05

    Plasmodium vivax remains a potential cause of morbidity and mortality for people living in its endemic areas. Understanding the genetic diversity of P. vivax from different regions is valuable for studying population dynamics and tracing the origins of parasites. The PvMSP-1 gene is highly polymorphic and has been used as a marker in many P. vivax population studies. The aim of this study was to investigate the genetic diversity of the PvMSP-1 gene icb5-6 fragment and to provide more genetic polymorphism data for further studies on P. vivax population structure and tracking of the origin of clinical cases. Nested PCR and sequencing of the PvMSP-1 icb5-6 marker were performed to obtain the nucleotide sequences of 95 P. vivax isolates collected from Zhejiang province, China. To investigate the genetic diversity of PvMSP-1, the 95 nucleotide sequences of the PvMSP-1 icb5-6 fragment were genotyped and analyzed using DnaSP v5, MEGA software. The 95 P. vivax isolates collected from Zhejiang province were either indigenous cases or imported cases from different regions around the world. A total of 95 sequences ranging from 390 to 460 bp were obtained. The 95 sequences were genotyped into four allele-types (Sal I, Belem, R-III and R-IV) and 17 unique haplotypes. R-III and Sal I were the predominant allele-types. The haplotype diversity (Hd) and nucleotide diversity (Pi) were estimated to be 0.729 and 0.062, indicating that the PvMSP-1 icb5-6 fragment had the highest level of polymorphism due to frequent recombination processes and single nucleotide polymorphism. The values of dN/dS and Tajima's D both suggested neutral selection for the PvMSP-1icb5-6 fragment. In addition, a rare recombinant style of R-IV type was identified. This study presented high genetic diversity in the PvMSP-1 marker among P. vivax strains from around the world. The genetic data is valuable for expanding the polymorphism information on P. vivax, which could be helpful for further study on

  1. Pure versus combined Merkel cell carcinomas: immunohistochemical evaluation of cellular proteins (p53, Bcl-2, and c-kit) reveals significant overexpression of p53 in combined tumors.

    Science.gov (United States)

    Lai, Jonathan H; Fleming, Kirsten E; Ly, Thai Yen; Pasternak, Sylvia; Godlewski, Marek; Doucette, Steve; Walsh, Noreen M

    2015-09-01

    Merkel cell polyomavirus is of oncogenic significance in approximately 80% of Merkel cell carcinomas. Morphological subcategories of the tumor differ in regard to viral status, the rare combined type being uniformly virus negative and the predominant pure type being mainly virus positive. Indications that different biological subsets of the tumor exist led us to explore this diversity. In an Eastern Canadian cohort of cases (75 patients; mean age, 76 years [range, 43-91]; male/female ratio, 43:32; 51 [68%] pure and 24 [34%] combined tumors), we semiquantitatively compared the immunohistochemical expression of 3 cellular proteins (p53, Bcl-2, and c-kit) in pure versus combined groups. Viral status was known in a subset of cases. The significant overexpression of p53 in the combined group (mean [SD], 153.8 [117.8] versus 121.6 [77.9]; P = .01) and the increased epidermal expression of this protein (p53 patches) in the same group lend credence to a primary etiologic role for sun damage in these cases. Expression of Bcl-2 and c-kit did not differ significantly between the 2 morphological groups. A relative increase in c-kit expression was significantly associated with a virus-negative status (median [interquartile range], 100 [60-115] versus 70 [0-100]; P = .03). Emerging data reveal divergent biological pathways in Merkel cell carcinoma, each with a characteristic immunohistochemical profile. Virus-positive tumors (all pure) exhibit high retinoblastoma protein and low p53 expression, whereas virus-negative cases (few pure and all combined) show high p53 and relatively high c-kit expression. The potential biological implications of this dichotomy call for consistent stratification of these tumors in future studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Blocking S1P interaction with S1P1 receptor by a novel competitive S1P1-selective antagonist inhibits angiogenesis

    International Nuclear Information System (INIS)

    Fujii, Yasuyuki; Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi; Igarashi, Yasuyuki; Goitsuka, Ryo

    2012-01-01

    Highlights: ► The effect of a newly developed S1P 1 -selective antagonist on angiogenic responses. ► S1P 1 is a critical component of VEGF-related angiogenic responses. ► S1P 1 -selective antagonist showed in vitro activity to inhibit angiogenesis. ► S1P 1 -selective antagonist showed in vivo activity to inhibit angiogenesis. ► The efficacy of S1P 1 -selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P 1 ) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P 1 and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P 1 -selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P 1 antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P 1 is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

  3. Crystallization and preliminary X-ray analysis of coagulation factor IX-binding protein from habu snake venom at pH 6.5 and 4.6

    International Nuclear Information System (INIS)

    Suzuki, Nobuhiro; Shikamoto, Yasuo; Fujimoto, Zui; Morita, Takashi; Mizuno, Hiroshi

    2004-01-01

    Crystals of habu coagulation factor IX-binding protein have been obtained at pH 6.5 and 4.6 and characterized by X-ray diffraction. Coagulation factor IX-binding protein isolated from Trimeresurus flavoviridis (IX-bp) is a C-type lectin-like protein. It is an anticoagulant protein consisting of homologous subunits A and B. The subunits both contain a Ca 2+ -binding site with differing affinity (K d values of 14 and 130 µM at pH 7.5). These binding characteristics are pH-dependent; under acidic conditions, the affinity of the low-affinity site was reduced considerably. In order to identify which site has high affinity and also to investigate the Ca 2+ -releasing mechanism, IX-bp was crystallized at pH 6.5 and 4.6. The crystals at pH 6.5 and 4.6 diffracted to 1.72 and 2.29 Å resolution, respectively; the former crystals belong to the monoclinic space group P2 1 , with unit-cell parameters a = 60.7, b = 63.5, c = 66.9 Å, β = 117.0°, while the latter belong to the monoclinic space group C2, with a = 134.1, b = 37.8, c = 55.8 Å, β = 110.4°

  4. Energy-Transfer Kinetics for Xe (6p[1/2]0) Atoms in Kr, Ar, Ne, and He.

    Science.gov (United States)

    He, Shan; Liu, Dong; Li, Xueyang; Chu, Junzhi; Guo, Jingwei; Liu, Jinbo; Hu, Shu; Sang, Fengting; Jin, Yuqi

    2018-06-11

    The kinetic processes for the Xe (6p[1/2] 0 ) atoms in Kr, Ar, Ne, and He buffer gases were studied. We found that Kr, Ar, and Ne atoms can be used to switch the amplified spontaneous emission (ASE) channel from 3408 nm (6p[1/2] 0 -6s'[1/2] 1 ) to 3680 nm (5d[1/2] 1 -6p[1/2] 1 ), while Xe and He atoms do not show such a phenomenon. This ASE channel switch is mainly ascribed to the fast transfer of 6p[1/2] 0 → 5d[1/2] 1 . On the basis of the rate equations for two-state coupling (energy-transfer processes between the two states are very rapid), the reason why the ASE channel switch effect normally coincides with a double exponential decay of the spontaneous emission at 828 nm (6p[1/2] 0 -6s[3/2] 1 ) is explained. The actual situations in Xe, Ar, Ne, and He follow this rule. However, the strictly single exponential decay of the spontaneous emission at 828 nm and strong ASE channel switch effect simultaneously emerge in Kr. This indicates that the transfer of 6p[1/2] 0 → 5d[1/2] 1 in Kr does not occur via two-state coupling, but via two steps of near-resonance collision through the 5s[3/2] 2 (Kr) state as the intermediate state (6p[1/2] 0 → 5s[3/2] 2 (Kr) → 5d[1/2] 1 ). In addition, we found Xe (6p[1/2] 0 ) atoms strongly tend to reach the 6p[3/2] 2 , 6p[3/2] 1 , and 6p[5/2] 2 states through the 5s[3/2] 2 (Kr) state as the intermediate state in Kr. The 5s[3/2] 2 (Kr) state plays a very important role in the energy-transfer kinetics for the Xe (6p[1/2] 0 ) atoms. Kr is probably an excellent buffer gas for laser systems based on Xe.

  5. Multitaxon activity profiling reveals differential microbial response to reduced seawater pH and oil pollution.

    Science.gov (United States)

    Coelho, Francisco J R C; Cleary, Daniel F R; Costa, Rodrigo; Ferreira, Marina; Polónia, Ana R M; Silva, Artur M S; Simões, Mário M Q; Oliveira, Vanessa; Gomes, Newton C M

    2016-09-01

    There is growing concern that predicted changes to global ocean chemistry will interact with anthropogenic pollution to significantly alter marine microbial composition and function. However, knowledge of the compounding effects of climate change stressors and anthropogenic pollution is limited. Here, we used 16S and 18S rRNA (cDNA)-based activity profiling to investigate the differential responses of selected microbial taxa to ocean acidification and oil hydrocarbon contamination under controlled laboratory conditions. Our results revealed that a lower relative abundance of sulphate-reducing bacteria (Desulfosarcina/Desulfococcus clade) due to an adverse effect of seawater acidification and oil hydrocarbon contamination (reduced pH-oil treatment) may be coupled to changes in sediment archaeal communities. In particular, we observed a pronounced compositional shift and marked reduction in the prevalence of otherwise abundant operational taxonomic units (OTUs) belonging to the archaeal Marine Benthic Group B and Marine Hydrothermal Vent Group (MHVG) in the reduced pH-oil treatment. Conversely, the abundance of several putative hydrocarbonoclastic fungal OTUs was higher in the reduced pH-oil treatment. Sediment hydrocarbon profiling, furthermore, revealed higher concentrations of several alkanes in the reduced pH-oil treatment, corroborating the functional implications of the structural changes to microbial community composition. Collectively, our results advance the understanding of the response of a complex microbial community to the interaction between reduced pH and anthropogenic pollution. In future acidified marine environments, oil hydrocarbon contamination may alter the typical mixotrophic and k-/r-strategist composition of surface sediment microbiomes towards a more heterotrophic state with lower doubling rates, thereby impairing the ability of the ecosystem to recover from acute oil contamination events. © 2016 John Wiley & Sons Ltd.

  6. Cullin1-P is an Essential Component of Non-Self Recognition System in Self-Incompatibility in Petunia.

    Science.gov (United States)

    Kubo, Ken-Ichi; Tsukahara, Mai; Fujii, Sota; Murase, Kohji; Wada, Yuko; Entani, Tetsuyuki; Iwano, Megumi; Takayama, Seiji

    2016-11-01

    Self-incompatibility (SI) in flowering plants is a genetic reproductive barrier to distinguish self- and non-self pollen to promote outbreeding. In Solanaceae, self-pollen is rejected by the ribonucleases expressed in the styles (S-RNases), via its cytotoxic function. On the other side, the male-determinant is the S-locus F-box proteins (SLFs) expressed in pollen. Multiple SLFs collaboratively detoxify non-self S-RNases, therefore, non-self recognition is the mode of self-/non-self discrimination in Solanaceae. It is considered that SLFs function as a substrate-recognition module of the Skp1-Cullin1-F-box (SCF) complex that inactivates non-self S-RNases via their polyubiquitination, which leads to degradation by 26S proteasome. In fact, PhSSK1 (Petunia hybrida SLF-interacting Skp1-like1) was identified as a specific component of SCF SLF and was shown to be essential for detoxification of S-RNase in Petunia However, different molecules are proposed as the candidate Cullin1, another component of SCF SLF , and there is as yet no definite conclusion. Here, we identified five Cullin1s from the expressed sequence tags (ESTs) derived from the male reproductive organ in Petunia Among them, only PhCUL1-P was co-immunoprecipitated with S 7 -SLF2. In vitro protein-binding assay suggested that PhSSK1 specifically forms a complex with PhCUL1-P in an SLF-dependent manner. Knockdown of PhCUL1-P suppressed fertility of transgenic pollen in cross-compatible pollination in the functional S-RNase-dependent manner. These results suggested that SCF SLF selectively uses PhCUL1-P. Phylogeny of Cullin1s indicates that CUL1-P is recruited into the SI machinery during the evolution of Solanaceae, suggesting that the SI components have evolved differently among species in Solanaceae and Rosaceae, despite both families sharing the S-RNase-based SI. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For

  7. In vitro kinetics of P700+ reduction of Thermosynechococcus elongatus trimeric Photosystem I complexes by recombinant cytochrome c 6 using a Joliot-type LED spectrophotometer.

    Science.gov (United States)

    Nguyen, Khoa; Vaughn, Michael; Frymier, Paul; Bruce, Barry D

    2017-01-01

    The reduction rate of photo-oxidized Photosystem I (PSI) with various natural and artificial electron donors have been well studied by transient absorption spectroscopy. The electron transfer rate from various donors to P 700 + has been measured for a wide range of photosynthetic organisms encompassing cyanobacteria, algae, and plants. PSI can be a limiting component due to tedious extraction and purification methods required for this membrane protein. In this report, we have determined the in vivo, intracellular cytochrome c 6 (cyt c 6 )/PSI ratio in Thermosynechococcus elongatus (T.e.) using quantitative Western blot analysis. This information permitted the determination of P 700 + reduction kinetics via recombinant cyt c 6 in a physiologically relevant ratio (cyt c 6 : PSI) with a Joliot-type, LED-driven, pump-probe spectrophotometer. Dilute PSI samples were tested under varying cyt c 6 concentration, temperature, pH, and ionic strength, each of which shows similar trends to the reported literature utilizing much higher PSI concentrations with laser-based spectrophotometer. Our results do however indicate kinetic differences between actinic light sources (laser vs. LED), and we have attempted to resolve these effects by varying our LED light intensity and duration. The standardized configuration of this spectrophotometer will also allow a more uniform kinetic analysis of samples in different laboratories. We can conclude that our findings from the LED-based system display an added total protein concentration effect due to multiple turnover events of P 700 + reduction by cyt c 6 during the longer illumination regime.

  8. Structural and Functional Analysis of the Signal-Transducing Linker in the pH-Responsive One-Component System CadC of Escherichia coli.

    Science.gov (United States)

    Buchner, Sophie; Schlundt, Andreas; Lassak, Jürgen; Sattler, Michael; Jung, Kirsten

    2015-07-31

    The pH-responsive one-component signaling system CadC in Escherichia coli belongs to the family of ToxR-like proteins, whose members share a conserved modular structure, with an N-terminal cytoplasmic winged helix-turn-helix DNA-binding domain being followed by a single transmembrane helix and a C-terminal periplasmic pH-sensing domain. In E. coli CadC, a cytoplasmic linker comprising approximately 50 amino acids is essential for transmission of the signal from the sensor to the DNA-binding domain. However, the mechanism of transduction is poorly understood. Using NMR spectroscopy, we demonstrate here that the linker region is intrinsically disordered in solution. Furthermore, mutational analyses showed that it tolerates a range of amino acid substitutions (altering polarity, rigidity and α-helix-forming propensity), is robust to extension but is sensitive to truncation. Indeed, truncations either reversed the expression profile of the target operon cadBA or decoupled expression from external pH altogether. CadC dimerizes via its periplasmic domain, but light-scattering analysis provided no evidence for dimerization of the isolated DNA-binding domain, with or without the linker region. However, bacterial two-hybrid analysis revealed that CadC forms stable dimers in a stimulus- and linker-dependent manner, interacting only at pHpH. Thus, we propose that the disordered CadC linker is required for transducing the pH-dependent response of the periplasmic sensor into a structural rearrangement that facilitates dimerization of the cytoplasmic CadC DNA-binding domain. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Chemical constituents from Bakeridesia pickelii Monteiro (Malvaceae) and the relaxant activity of kaempferol-3-O-β-D-(6''-E-p -coumaroyl) glucopyranoside on guinea-pig ileum

    International Nuclear Information System (INIS)

    Costa, Danielly Albuquerque da; Silva, Davi Antas e; Cavalcanti, Aline Coutinho; Medeiros, Marcos Antonio Alves de; Lima, Julianeli Tolentino de; Cavalcante, Jose Marcilio Sobral; Silva, Bagnolia Araujo da; Agra, Maria de Fatima; Souza, Maria de Fatima Vanderlei de

    2007-01-01

    The phytochemical investigation of Bakeridesia pickelii Monteiro led to the isolation of seven compounds: β-sitosterol, a mixture of sitosteryl-3-O-β-D-glucopyranoside and stigmasteryl-3-O-β-D-glucopyranoside, vanillic acid, p-coumaric acid, quercetin 3-O-β-D-glucopyranoside (isoquercitrin) and kaempferol-3-O-β-D-(6 - E-p -coumaroyl) glucopyranoside (tiliroside), which was isolated as the major component. Their structures were elucidated on the basis of spectroscopic data such as IR, 1 H and 13 C NMR, including two-dimensional techniques. Tiliroside relaxed the guinea-pig ileum pre-contracted with KCl 40 mM (EC 50 = 9.5 ± 1.0 x 10 -5 M), acetylcholine 10 -6 M (EC 50 = 2.3 ± 0.9 x 10 -5 M) or histamine 10 -6 M (EC 50 = 4.1 ± 1.0 x 10 -5 M) in a concentration-dependent manner. (author)

  10. Chemical constituents from Bakeridesia pickelii Monteiro (Malvaceae and the relaxant activity of kaempferol-3-O-beta-D-(6"-E-p -coumaroyl glucopyranoside on guinea-pig ileum

    Directory of Open Access Journals (Sweden)

    Danielly Albuquerque da Costa

    2007-08-01

    Full Text Available The phytochemical investigation of Bakeridesia pickelii Monteiro led to the isolation of seven compounds: beta-sitosterol, a mixture of sitosteryl-3-O-beta-D-glucopyranoside and stigmasteryl-3-O-beta-D-glucopyranoside, vanillic acid, p-coumaric acid, quercetin 3-O-beta-D-glucopyranoside (isoquercitrin and kaempferol-3-O-beta-D-(6"-E-p -coumaroyl glucopyranoside (tiliroside, which was isolated as the major component. Their structures were elucidated on the basis of spectroscopic data such as IR, ¹H and 13C NMR, including two-dimensional techniques. Tiliroside relaxed the guinea-pig ileum pre-contracted with KCl 40 mM (EC50 = 9.5 ± 1.0 x 10-5 M, acetylcholine 10-6 M (EC50 = 2.3 ± 0.9 x 10-5 M or histamine 10-6 M (EC50 = 4.1 ± 1.0 x 10-5 M in a concentration-dependent manner.

  11. Estimation of the binding modes with important human cytochrome P450 enzymes, drug interaction potential, pharmacokinetics, and hepatotoxicity of ginger components using molecular docking, computational, and pharmacokinetic modeling studies.

    Science.gov (United States)

    Qiu, Jia-Xuan; Zhou, Zhi-Wei; He, Zhi-Xu; Zhang, Xueji; Zhou, Shu-Feng; Zhu, Shengrong

    2015-01-01

    Ginger is one of the most commonly used herbal medicines for the treatment of numerous ailments and improvement of body functions. It may be used in combination with prescribed drugs. The coadministration of ginger with therapeutic drugs raises a concern of potential deleterious drug interactions via the modulation of the expression and/or activity of drug-metabolizing enzymes and drug transporters, resulting in unfavorable therapeutic outcomes. This study aimed to determine the molecular interactions between 12 main active ginger components (6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol, 10-shogaol, ar-curcumene, β-bisabolene, β-sesquiphelandrene, 6-gingerdione, (-)-zingiberene, and methyl-6-isogingerol) and human cytochrome P450 (CYP) 1A2, 2C9, 2C19, 2D6, and 3A4 and to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the 12 ginger components using computational approaches and comprehensive literature search. Docking studies showed that ginger components interacted with a panel of amino acids in the active sites of CYP1A2, 2C9, 2C19, 2D6, and 3A4 mainly through hydrogen bond formation, to a lesser extent, via π-π stacking. The pharmacokinetic simulation studies showed that the [I]/[Ki ] value for CYP2C9, 2C19, and 3A4 ranged from 0.0002 to 19.6 and the R value ranged from 1.0002 to 20.6 and that ginger might exhibit a high risk of drug interaction via inhibition of the activity of human CYP2C9 and CYP3A4, but a low risk of drug interaction toward CYP2C19-mediated drug metabolism. Furthermore, it has been evaluated that the 12 ginger components possessed a favorable ADMET profiles with regard to the solubility, absorption, permeability across the blood-brain barrier, interactions with CYP2D6, hepatotoxicity, and plasma protein binding. The validation results showed that there was no remarkable effect of ginger on the metabolism of warfarin in humans, whereas concurrent use of ginger and nifedipine exhibited a

  12. LncMAPK6 drives MAPK6 expression and liver TIC self-renewal.

    Science.gov (United States)

    Huang, Guanqun; Jiang, Hui; He, Yueming; Lin, Ye; Xia, Wuzheng; Luo, Yuanwei; Liang, Min; Shi, Boyun; Zhou, Xinke; Jian, Zhixiang

    2018-05-15

    Liver tumor initiating cells (TICs) have self-renewal and differentiate capacities, and largely contribute to tumor initiation, metastasis and drug resistance. MAPK signaling is a critical pathway in many biological processes, while its role in liver TICs hasn't been explored. Online-available dataset was used for unbiased screening. Liver TICs were examined CD133 FACS or oncosphere formation. TIC self-renewal was detected by oncosphere formation and tumor initiation assay. LncRNA function was detected by loss of function or gain of function assays. The molecular mechanism of lncRNA was explored by RNA pulldown, RNA immunoprecipitation, ChIP, western blot and double FISH. Here, we examined the expression profiles of MAPK components (MAPKs, MAP2Ks, MAP3Ks, MAP4Ks), and found MAPK6 is most highly expressed in liver cancer samples. Moreover, a divergent lncRNA (long noncoding RNA) of MAPK6, termed lncMAPK6 here, is also overexpressed along with liver tumorigenesis. LncMAPK6 promotes liver tumor propagation and TIC self-renewal through MAPK6. LncMAPK6 interacts with and recruits RNA polymerase II to MAPK6 promoter, and finally activates the transcription of MAPK6. Through MAPK6 transcriptional regulation, lncMAPK6 drives MARK signaling activation. LncMAPK6-MAPK6 pathway can be used for liver TIC targeting. Altogether, lncMAPK6 promotes MARK signaling and the self-renewal of liver TICs through MAPK6 expression. MAPK6 was the most highly expressed MAPK component in liver cancer and liver TICs and lncMAPK6 participated in the transcriptional regulation of MAPK6in cis. This work revealed the importance role of MAPK signaling in liver TIC self-renewal and added a new layer for liver TIC and MAPK6 expression regulation.

  13. Computational studies on LiP H isolated from Ganoderma lucidum GD88

    Directory of Open Access Journals (Sweden)

    Parambayil Nayana

    2015-01-01

    Full Text Available Ganoderma lucidum is a basidiomycete fungus that produces ligninase for the modification of lignin. Lignin peroxidase (LiP is a glycoprotein that acts on the recalcitrant cell wall component lignin. In the present study, the phylogenetic analysis of Ganoderma lucidum GD88 with the partial coding sequence (cds of other LiP isoforms was performed using MEGA6. After determination of the open reading frame, the +3 frame nucleotide sequence was converted to protein using the EMBOSS Transseq and the secondary structure was predicted using the Chou and Fasman Secondary Structure Prediction server (CFSSP. Protein modeling was also performed by SWISS-MODEL. The obtained result shows that the lipH partial cds of Ganoderma lucidum GD88 is homologous to the lipD gene of Phanerochaete chrysosporium. The secondary structure prediction result revealed that the percent content of the helix (67 is higher than the percent contents of sheet (53.4 and turns (13.6. According to the generated model, LiP H protein is a homodimer with chains A and B. The heme acts as a ligand and plays a major role in structure stabilization.

  14. Molecular Nickel Phosphide Carbonyl Nanoclusters: Synthesis, Structure, and Electrochemistry of [Ni11P(CO)18]3- and [H6-nNi31P4(CO)39]n- (n = 4 and 5).

    Science.gov (United States)

    Capacci, Chiara; Ciabatti, Iacopo; Femoni, Cristina; Iapalucci, Maria Carmela; Funaioli, Tiziana; Zacchini, Stefano; Zanotti, Valerio

    2018-02-05

    The reaction of [NEt 4 ] 2 [Ni 6 (CO) 12 ] in thf with 0.5 equiv of PCl 3 affords the monophosphide [Ni 11 P(CO) 18 ] 3- that in turn further reacts with PCl 3 resulting in the tetra-phosphide carbonyl cluster [HNi 31 P 4 (CO) 39 ] 5- . Alternatively, the latter can be obtained from the reaction of [NEt 4 ] 2 [Ni 6 (CO) 12 ] in thf with 0.8-0.9 equiv of PCl 3 . The [HNi 31 P 4 (CO) 39 ] 5- penta-anion is reversibly protonated by strong acids leading to the [H 2 Ni 31 P 4 (CO) 39 ] 4- tetra-anion, whereas deprotonation affords the [Ni 31 P 4 (CO) 39 ] 6- hexa-anion. The latter is reduced with Na/naphthalene yielding the [Ni 31 P 4 (CO) 39 ] 7- hepta-anion. In order to shed light on the polyhydride nature and redox behavior of these clusters, electrochemical and spectroelectrochemical studies were carried out on [Ni 11 P(CO) 18 ] 3- , [HNi 31 P 4 (CO) 39 ] 5- , and [H 2 Ni 31 P 4 (CO) 39 ] 4- . The reversible formation of the stable [Ni 11 P(CO) 18 ] 4- tetra-anion is demonstrated through the spectroelectrochemical investigation of [Ni 11 P(CO) 18 ] 3- . The redox changes of [HNi 31 P 4 (CO) 39 ] 5- show features of chemical reversibility and the vibrational spectra in the ν CO region of the nine redox states of the cluster [HNi 31 P 4 (CO) 39 ] n- (n = 3-11) are reported. The spectroelectrochemical investigation of [H 2 Ni 31 P 4 (CO) 39 ] 4- revealed the presence of three chemically reversible reduction processes, and the IR spectra of [H 2 Ni 31 P 4 (CO) 39 ] n- (n = 4-7) have been recorded. The different spectroelectrochemical behavior of [HNi 31 P 4 (CO) 39 ] 5- and [H 2 Ni 31 P 4 (CO) 39 ] 4- support their formulations as polyhydrides. Unfortunately, all the attempts to directly confirm their poly hydrido nature by 1 H NMR spectroscopy failed, as previously found for related large metal carbonyl clusters. Thus, the presence and number of hydride ligands have been based on the observed protonation/deprotonation reactions and the spectroelectrochemical

  15. Chino del tomate virus:Relationships to Other Begomoviruses and Identification of A-Component Variants that Affect Symptom Expression.

    Science.gov (United States)

    Brown, J K; Ostrow, K M; Idris, A M; Stenger, D C

    2000-05-01

    Phylogenetic and distance analyses place Chino del tomate virus (CdTV) in the New World clade of begomoviruses and indicate that CdTV and Tomato leaf crumple virus (TLCrV) are closely related strains of the same virus. One cloned CdTV A component (pCdTV-H6), when inoculated to tomato with the B component (pCdTV-B52), produced mild symptoms and low DNA titers. Another cloned CdTV A component (pCdTV-H8), when coinoculated to tomato with the B component, produced moderate leaf curling and veinal chlorosis similar to that of TLCrV. Coinoculation of both CdTV A components and the B component to tomato produced wild-type chino del tomate (CdT) disease symptoms consisting of severe leaf curling, veinal and interveinal chlorosis, and stunting. The two CdTV A components were nearly identical, except at nucleotide positions 1,722 and 2,324. The polymorphism at nucleotide 1,722 resulted in a change at Rep amino acid 261. The second polymorphism at nucleotide 2,324 resulted in changes at Rep amino acid 60 and AC4 amino acid 10. Two chimeric A components constructed by reciprocal exchange of a fragment bearing the polymorphic site at nucleotide 1,722 were evaluated for symptom phenotype. One chimeric A component (pCdTV-H86) produced wild-type CdT symptoms when coinoculated to tomato with the B component. The reciprocal chimeric A component (pCdTV-H68), when coin-oculated to tomato with the B component, also produced severe leaf curling, veinal chlorosis, and stunting. However, pCdTV-H68 induced less obvious interveinal chlorosis than wild-type or pCdTV-H86. Examination of A component genotypes recovered from tomato coinoculated with pCdTV-H6 and pCdTV-H8 indicated that recombination occurred to produce a genotype identical to pCdTV-H86. These results indicate that subtle genotypic variation has significant effects on symptom expression and may explain phenotypic differences observed among isolates and cloned DNAs of CdTV and TLCrV.

  16. Magnetite synthesis from ferrous iron solution at pH 6.8 in a continuous stirred tank reactor.

    Science.gov (United States)

    Mos, Yvonne M; Zorzano, Karin Bertens; Buisman, Cees J N; Weijma, Jan

    2018-04-01

    Partial oxidation of defined Fe 2+ solutions is a well-known method for magnetite synthesis in batch systems. The partial oxidation method could serve as basis for an iron removal process in drinking water production, yielding magnetite (Fe 3 O 4 ) as a compact and valuable product. As a first step toward such a process, a series of experiments was carried out, in which magnetite was synthesized from an Fe 2+ solution in a 2 L continuous stirred tank reactor (CSTR) at atmospheric pressure and 32 °C. In four experiments, elevating the pH from an initial value of 5.5 or 6.0 to a final value of 6.8, 7.0 or 7.5 caused green rust to form, eventually leading to magnetite. Formation of NH 4 + in the reactor indicated that NO 3 - and subsequently NO 2 - served as the oxidant. However, mass flow analysis revealed an influx of O 2 to the reactor. In a subsequent experiment, magnetite formation was achieved in the absence of added nitrate. In another experiment, seeding with magnetite particles led to additional magnetite precipitation without the need for a pH elevation step. Our results show, for the first time, that continuous magnetite formation from an Fe 2+ solution is possible under mild conditions, without the need for extensive addition of chemicals.

  17. p62 regulates CD40-mediated NFκB activation in macrophages through interaction with TRAF6

    Energy Technology Data Exchange (ETDEWEB)

    Seibold, Kristina; Ehrenschwender, Martin, E-mail: martin.ehrenschwender@ukr.de

    2015-08-14

    CD40 is a member of the tumor necrosis factor (TNF) receptor family. Activation-induced recruitment of adapter proteins, so-called TNF-receptor-associated factors (TRAFs) to the cytoplasmic tail of CD40 triggers signaling cascades important in the immune system, but has also been associated with excessive inflammation in diseases such as atherosclerosis and rheumatoid arthritis. Especially, pro-inflammatory nuclear factor κB (NFκB) signaling emanating from CD40-associated TRAF6 appears to be a key pathogenic driving force. Consequently, targeting the CD40-TRAF6 interaction is emerging as a promising therapeutic strategy, but the underlying molecular machinery of this signaling axis is to date poorly understood. Here, we identified the multifunctional adaptor protein p62 as a critical regulator in CD40-mediated NFκB signaling via TRAF6. CD40 activation triggered formation of a TRAF6-p62 complex. Disturbing this interaction tremendously reduced CD40-mediated NFκB signaling in macrophages, while TRAF6-independent signaling pathways remained unaffected. This highlights p62 as a potential target in hyper-inflammatory, CD40-associated pathologies. - Highlights: • CD40 activation triggers interaction of the adapter protein TRAF6 with p62. • TRAF6-p62 interaction regulates CD40-mediated NFκB signaling in macrophages. • Defective TRAF6-p62 interaction reduces CD40-mediated NFκB activation in macrophages.

  18. Immobilisation of an antibacterial drug to Ti6Al4V components fabricated using selective laser melting

    Science.gov (United States)

    Vaithilingam, Jayasheelan; Kilsby, Samuel; Goodridge, Ruth D.; Christie, Steven D. R.; Edmondson, Steve; Hague, Richard J. M.

    2014-09-01

    Bacterial infections from biomedical implants and surgical devices are a major problem in orthopaedic, dental and vascular surgery. Although the sources of contaminations that lead to bacterial infections are known, it is not possible to control or avoid such infections completely. In this study, an approach to immobilise Ciprofloxacin® (an antibacterial drug) to phosphonic acid based self-assembled monolayers (SAMs) adsorbed on a selectively laser melted (SLM) Ti6Al4V structure, has been presented. X-ray photoelectron spectroscopy (XPS) and static water contact angle measurements confirmed the attachment of SAMs and the drug. Results showed that Ciprofloxacin® is highly stable under the oxidative conditions used in this study. In-vitro stability was estimated by immersing the Ciprofloxacin® immobilised substrates in 10 mM of Tris-HCl buffer (pH-7.4) for 42 days. The Tris-HCl buffer was analysed using UV-vis spectrophotometry at 7, 14, 28 and 42 day time intervals to determine the release of the immobilised drug. The drug was observed to release in a sustained manner. 50% of the drug was released after 4 weeks with approximately 40% of the drug remaining after 6 weeks. Antibacterial susceptibility tests revealed that the immobilised drug was therapeutically active upon its release. This study demonstrates the potential to use self-assembled monolayers to modify SLM fabricated surfaces with therapeutics.

  19. Underestimation of glucose turnover measured with [6-3H]- and [6,6-2H]- but not [6-14C]glucose during hyperinsulinemia in humans

    International Nuclear Information System (INIS)

    McMahon, M.M.; Schwenk, W.F.; Haymond, M.W.; Rizza, R.A.

    1989-01-01

    Recent studies indicate that hydrogen-labeled glucose tracers underestimate glucose turnover in humans under conditions of high flux. The cause of this underestimation is unknown. To determine whether the error is time-, pool-, model-, or insulin-dependent, glucose turnover was measured simultaneously with [6-3H]-, [6,6-2H2]-, and [6-14C]glucose during a 7-h infusion of either insulin (1 mU.kg-1.min-1) or saline. During the insulin infusion, steady-state glucose turnover measured with both [6-3H]glucose (8.0 +/- 0.5 mg.kg-1.min-1) and [6,6-2H2]glucose (7.6 +/- 0.5 mg.kg-1.min-1) was lower (P less than .01) than either the glucose infusion rate required to maintain euglycemia (9.8 +/- 0.7 mg.kg-1.min-1) or glucose turnover determined with [6-14C]glucose and corrected for Cori cycle activity (9.8 +/- 0.7 mg.kg-1.min-1). Consequently negative glucose production rates (P less than .01) were obtained with either [6-3H]- or [6,6-2H2]- but not [6-14C]glucose. The difference between turnover estimated with [6-3H]glucose and actual glucose disposal (or 14C glucose flux) did not decrease with time and was not dependent on duration of isotope infusion. During saline infusion, estimates of glucose turnover were similar regardless of the glucose tracer used. High-performance liquid chromatography of the radioactive glucose tracer and plasma revealed the presence of a tritiated nonglucose contaminant. Although the contaminant represented only 1.5% of the radioactivity in the [6-3H]glucose infusate, its clearance was 10-fold less (P less than .001) than that of [6-3H]glucose. This resulted in accumulation in plasma, with the contaminant accounting for 16.6 +/- 2.09 and 10.8 +/- 0.9% of what customarily is assumed to be plasma glucose radioactivity during the insulin or saline infusion, respectively (P less than .01)

  20. Recurrent Respiratory Papillomatosis : Clinical course and psychosocial aspects

    NARCIS (Netherlands)

    San Giorgi, Michel

    2017-01-01

    Recurrent Respiratory Papillomatosis (RRP) is een zeldzame ziekte, welke zich kenmerkt door wratachtige afwijkingen door de gehele luchtweg. Dit veroorzaakt stemproblemen en een bedreigde luchtweg. Patiënten zijn afhankelijk van herhaaldelijk chirurgisch ingrijpen. Dit proefschrift liet zien dat RRP

  1. Bi–Mn mixed metal organic oxide: A novel 3d-6p mixed metal coordination network

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Fa-Nian, E-mail: fshi@ua.pt [School of Science, Shenyang University of Technology, 110870 Shenyang (China); Department of Chemistry, CICECO, University of Aveiro, 3810-193 Aveiro (Portugal); Rosa Silva, Ana [Department of Chemistry, CICECO, University of Aveiro, 3810-193 Aveiro (Portugal); Bian, Liang [Key Laboratory of Functional Materials and Devices for Special Environments, Chinese Academy of Sciences, Urumqi 830011, Xinjiang (China)

    2015-05-15

    A new terminology of metal organic oxide (MOO) was given a definition as a type of coordination polymers which possess the feature of inorganic connectivity between metals and the direct bonded atoms and show 1D, 2D or 3D inorganic sub-networks. One such compound was shown as an example. A 3d-6p (Mn–Bi. Named MOOMnBi) mixed metals coordination network has been synthesized via hydrothermal method. The new compound with the molecular formula of [MnBi{sub 2}O(1,3,5-BTC){sub 2}]{sub n} (1,3,5-BTC stands for benzene-1,3,5-tricarboxylate) was characterized via single crystal X-ray diffraction technique that revealed a very interesting 3-dimensional (3D) framework with Bi{sub 4}O{sub 2}(COO){sub 12} clusters which are further connected to Mn(COO){sub 6} fragments into a 2D MOO. The topology study indicates an unprecedented topological type with the net point group of (4{sup 13}.6{sup 2})(4{sup 13}.6{sup 8})(4{sup 16}.6{sup 5})(4{sup 18}.6{sup 10})(4{sup 22}.6{sup 14})(4{sup 3}) corresponding to 3,6,7,7,8,9-c hexa-nodal net. MOOMnBi shows catalytic activity in the synthesis of (E)-α,β-unsaturated ketones. - Graphical abstract: This metal organic framework (MOF) is the essence of a 2D metal organic oxide (MOO). - Highlights: • New concept of metal organic oxide (MOO) was defined and made difference from metal organic framework. • New MOO of MOOMnBi was synthesized by hydrothermal method. • Crystal structure of MOOMnBi was determined by single crystal X-ray analysis. • The catalytic activity of MOOMnBi was studied showing reusable after 2 cycles.

  2. The anomalous chiral Lagrangian of order p6

    International Nuclear Information System (INIS)

    Bijnens, J.; Talavera, P.

    2002-01-01

    We construct the effective chiral Lagrangian for chiral perturbation theory in the mesonic odd-intrinsic-parity sector at order p 6 . The Lagrangian contains 24 in principle measurable terms and no contact terms for the general case of N f light flavors, 23 terms for three and 5 for two flavors. In the two flavor case we need a total of 13 terms if an external singlet vector field is included. We discuss and implement the methods used to reduce to a minimal set. The infinite parts needed for renormalization are calculated and presented as well. (orig.)

  3. 1991 P/M in aerospace and defense technologies; Proceedings of the Symposium, Tampa, FL, Mar. 4-6, 1991

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    The present conference discusses high-performance injection-molded metal components, the importance of phosphorus in P/M alloys, particle-metallurgy steels for antifriction bearings, P/M processing of metal-matrix composites (MMCs), SiC- and B4C-reinforced Mg MMCs for satellite applications, N13Al-based intermetallic MMCs, the synthesis and properties of nanophase ceramics, MMC spray-forming, the microstructure and properties of spray-cast Cu alloys, and the spray casting of hypoeutectic Cu-Cr alloy. Also discussed are the application of the Osprey preform process to light alloys and MMCs, P/M in lightweight aircraft engine components, the fabrication of oriented single-crystal wafer stock from Ni-Al-Mo-X alloy powders, higher-performance P/M Be materials for aerospace applications, the characteristics of electrodischarge compaction, and fatigue crack propagation in dispersion-strengthened P/M Al alloys at elevated and room temperatures

  4. Inositol-P6 induced structural changes in duck major haemoglobin

    African Journals Online (AJOL)

    Bamiji Babalola

    2011-11-02

    Nov 2, 2011 ... of duck (Anas platyrhinchos) have been carried out in the presence of ... dependence profile of the apparent second-order rate constant of both oxy- and ... Key words: 5,5‟-Dithiobis (2-nitrobenzoate), duck, haemoglobin, inositol-P6, sulphydryl group. ... Saigo, 1999), thereby making it possible to detect the.

  5. Molecular crosstalk between cancer cells and tumor microenvironment components suggests potential targets for new therapeutic approaches in mobile tongue cancer

    International Nuclear Information System (INIS)

    Dayan, Dan; Salo, Tuula; Salo, Sirpa; Nyberg, Pia; Nurmenniemi, Sini; Costea, Daniela Elena; Vered, Marilena

    2012-01-01

    We characterized tumor microenvironment (TME) components of mobile tongue (MT) cancer patients in terms of overall inflammatory infiltrate, focusing on the protumorigenic/anti-inflammatory phenotypes and on cancer-associated fibroblasts (CAFs) in order to determine their interrelations and associations with clinical outcomes. In addition, by culturing tongue carcinoma cells (HSC-3) on a three-dimensional myoma organotypic model that mimics TME, we attempted to investigate the possible existence of a molecular crosstalk between cancer cells and TME components. Analysis of 64 cases of MT cancer patients revealed that the overall density of the inflammatory infiltrate was inversely correlated to the density of CAFs (P = 0.01), but that the cumulative density of the protumorigenic/anti-inflammatory phenotypes, including regulatory T cells (Tregs, Foxp3+), tumor-associated macrophages (TAM2, CD163+), and potentially Tregs-inducing immune cells (CD80+), was directly correlated with the density of CAFs (P = 0.01). The hazard ratio (HR) for recurrence in a TME rich in CD163+ Foxp3+ CD80+ was 2.9 (95% CI 1.03–8.6, P = 0.043 compared with low in CD163+ Foxp3+ CD80+). The HR for recurrence in a TME rich in CAFs was 4.1 (95% confidence interval [CI] 1.3–12.8, P = 0.012 compared with low in CAFs). In vitro studies showed cancer-derived exosomes, epithelial–mesenchymal transition process, fibroblast-to-CAF-like cell transdifferentiation, and reciprocal interrelations between different cytokines suggesting the presence of molecular crosstalk between cancer cells and TME components. Collectively, these results highlighted the emerging need of new therapies targeting this crosstalk between the cancer cells and TME components in MT cancer

  6. Tribological Performance Optimization of Electroless Ni-P-W Coating Using Weighted Principal Component Analysis

    Directory of Open Access Journals (Sweden)

    S. Roy

    2013-12-01

    Full Text Available The present investigation is an experimental approach to deposit electroless Ni-P-W coating on mild steel substrate and find out the optimum combination of various tribological performances on the basis of minimum friction and wear, using weighted principal component analysis (WPCA. In this study three main tribological parameters are chosen viz. load (A, speed (B and time(C. The responses are coefficient of friction and wear depth. Here Weighted Principal Component Analysis (WPCA method is adopted to convert the multi-responses into single performance index called multiple performance index (MPI and Taguchi L27 orthogonal array is used to design the experiment and to find the optimum combination of tribological parameters for minimum coefficient of friction and wear depth. ANOVA is performed to find the significance of the each tribological process parameters and their interactions. The EDX analysis, SEM and XRD are performed to study the composition and structural aspects.

  7. The change of p16 gene expression in glioma cell line C6 after radiation with gamma knife

    International Nuclear Information System (INIS)

    Zhao Xingli; Zhao Conghai; Tian Yu

    2002-01-01

    Objective: T observe the change of expression of p16 gene product, P16 protein, after treated by gamma knife on glioma cell line C6. Methods: Glioma C6 cells proliferated in vitro, treated by γ-knife in dose of 5.00 and 6.22 Gy, respectively. P16 protein was detected by immunohistochemical technique and image analysis. Results: The P16 protein in glioma C6 cells was notably increased after treatment with γ knife (P < 0.01). The grey number in C6 group (control group) was 167.1 +- 6.2 and was 155.4 +- 2.0 and 124.9 +- 7.1, respectively, in 5.00 Gy and 6.22 Gy gamma knife treated group. Conclusion: It is suggests that one of the mechanisms of glioma cell C6 apoptosis induced by γ-knife radiation may be associated with activation of p16 gene and increase of P16 protein expression

  8. A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway.

    Science.gov (United States)

    Salašová, Alena; Yokota, Chika; Potěšil, David; Zdráhal, Zbyněk; Bryja, Vítězslav; Arenas, Ernest

    2017-07-11

    Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients. Co-immunoprecipitation and tandem mass spectrometry was performed in a mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to identify novel LRRK2 binding partners. Inhibition of the WNT/β-catenin reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus laevis' early development. Our proteomic analysis identified that LRRK2 interacts with proteins involved in WNT/PCP signaling such as the PDZ domain-containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells in vitro and in the mouse ventral midbrain in vivo. Moreover, co-immunoprecipitation analysis revealed that LRRK2 binds to two core components of the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and CULLIN-3, which regulate WNT secretion and inhibit WNT/β-catenin signaling, respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and act as dual regulators of WNT/PCP and β-catenin signaling. Accordingly, analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not only inhibits WNT/β-catenin pathway, but induces a classical WNT/PCP phenotype in vivo. Our study shows for the first time that LRRK2 activates the WNT

  9. The energy structure and decay channels of the 4p6-shell excited states in Sr

    Science.gov (United States)

    Kupliauskienė, A.; Kerevičius, G.; Borovik, V.; Shafranyosh, I.; Borovik, A.

    2017-11-01

    The ejected-electron spectra arising from the decay of the 4p{}5{{nln}}{\\prime }{l}{\\prime }{n}{\\prime\\prime }{l}{\\prime\\prime } autoionizing states in Sr atoms have been studied precisely at the incident-electron energies close to excitation and ionization thresholds of the 4{{{p}}}6 subshell. The excitation behaviors for 58 lines observed between 12 and 21 eV ejected-electron kinetic energy have been investigated. Also, the ab initio calculations of excitation energies, autoionization probabilities and electron-impact excitation cross sections of the states 4p{}5{{nln}}{\\prime }{l}{\\prime }{n}{\\prime\\prime }{l}{\\prime\\prime } (nl = 4d, 5s, 5p; {n}{\\prime }{l}{\\prime } = 4d, 5s, 5p; {n}{\\prime\\prime }{l}{\\prime\\prime } = 5s, 6s, 7s, 8s, 9s, 5p, 6p, 5d, 6d, 7d, 8d, 4f, 5g) have been performed by employing the large-scale configuration-interaction method in the basis of the solutions of Dirac-Fock-Slater equations. The obtained experimental and theoretical data have been used for the accurate identification of the 60 lines in ejected-electron spectra and the 68 lines observed earlier in photoabsorption spectra. The excitation and decay processes for 105 classified states in the 4p55s{}2{nl}, 4p54d{}2{nl} and 4p55s{{nln}}{\\prime }{l}{\\prime } configurations have been considered in detail. In particular, most of the states lying below the ionization threshold of the 4p6 subshell at 26.92 eV possess up to four decay channels with formation of Sr+ in 5s{}1/2, 4d{}3/{2,5/2} and 5p{}1/{2,3/2} states. Two-step autoionization and two-electron Auger transitions with formation of Sr2+ in the 4p6 {}1{{{S}}}0 ground state are the main decay paths for high-lying autoionizing states. The excitation threshold of the 4{{{p}}}6 subshell in Sr has been established at 20.98 ± 0.05 eV.

  10. Six Month In Situ High-Resolution Carbonate Chemistry and Temperature Study on a Coral Reef Flat Reveals Asynchronous pH and Temperature Anomalies.

    Directory of Open Access Journals (Sweden)

    David I Kline

    Full Text Available Understanding the temporal dynamics of present thermal and pH exposure on coral reefs is crucial for elucidating reef response to future global change. Diel ranges in temperature and carbonate chemistry parameters coupled with seasonal changes in the mean conditions define periods during the year when a reef habitat is exposed to anomalous thermal and/or pH exposure. Anomalous conditions are defined as values that exceed an empirically estimated threshold for each variable. We present a 200-day time series from June through December 2010 of carbonate chemistry and environmental parameters measured on the Heron Island reef flat. These data reveal that aragonite saturation state, pH, and pCO2 were primarily modulated by biologically-driven changes in dissolved organic carbon (DIC and total alkalinity (TA, rather than salinity and temperature. The largest diel temperature ranges occurred in austral spring, in October (1.5 - 6.6°C and lowest diel ranges (0.9 - 3.2°C were observed in July, at the peak of winter. We observed large diel total pH variability, with a maximum range of 7.7 - 8.5 total pH units, with minimum diel average pH values occurring during spring and maximum during fall. As with many other reefs, the nighttime pH minima on the reef flat were far lower than pH values predicted for the open ocean by 2100. DIC and TA both increased from June (end of Fall to December (end of Spring. Using this high-resolution dataset, we developed exposure metrics of pH and temperature individually for intensity, duration, and severity of low pH and high temperature events, as well as a combined metric. Periods of anomalous temperature and pH exposure were asynchronous on the Heron Island reef flat, which underlines the importance of understanding the dynamics of co-occurrence of multiple stressors on coastal ecosystems.

  11. Six Month In Situ High-Resolution Carbonate Chemistry and Temperature Study on a Coral Reef Flat Reveals Asynchronous pH and Temperature Anomalies.

    Science.gov (United States)

    Kline, David I; Teneva, Lida; Hauri, Claudine; Schneider, Kenneth; Miard, Thomas; Chai, Aaron; Marker, Malcolm; Dunbar, Rob; Caldeira, Ken; Lazar, Boaz; Rivlin, Tanya; Mitchell, Brian Gregory; Dove, Sophie; Hoegh-Guldberg, Ove

    2015-01-01

    Understanding the temporal dynamics of present thermal and pH exposure on coral reefs is crucial for elucidating reef response to future global change. Diel ranges in temperature and carbonate chemistry parameters coupled with seasonal changes in the mean conditions define periods during the year when a reef habitat is exposed to anomalous thermal and/or pH exposure. Anomalous conditions are defined as values that exceed an empirically estimated threshold for each variable. We present a 200-day time series from June through December 2010 of carbonate chemistry and environmental parameters measured on the Heron Island reef flat. These data reveal that aragonite saturation state, pH, and pCO2 were primarily modulated by biologically-driven changes in dissolved organic carbon (DIC) and total alkalinity (TA), rather than salinity and temperature. The largest diel temperature ranges occurred in austral spring, in October (1.5 - 6.6°C) and lowest diel ranges (0.9 - 3.2°C) were observed in July, at the peak of winter. We observed large diel total pH variability, with a maximum range of 7.7 - 8.5 total pH units, with minimum diel average pH values occurring during spring and maximum during fall. As with many other reefs, the nighttime pH minima on the reef flat were far lower than pH values predicted for the open ocean by 2100. DIC and TA both increased from June (end of Fall) to December (end of Spring). Using this high-resolution dataset, we developed exposure metrics of pH and temperature individually for intensity, duration, and severity of low pH and high temperature events, as well as a combined metric. Periods of anomalous temperature and pH exposure were asynchronous on the Heron Island reef flat, which underlines the importance of understanding the dynamics of co-occurrence of multiple stressors on coastal ecosystems.

  12. The radish gene reveals a memory component with variable temporal properties.

    Directory of Open Access Journals (Sweden)

    Holly LaFerriere

    Full Text Available Memory phases, dependent on different neural and molecular mechanisms, strongly influence memory performance. Our understanding, however, of how memory phases interact is far from complete. In Drosophila, aversive olfactory learning is thought to progress from short-term through long-term memory phases. Another memory phase termed anesthesia resistant memory, dependent on the radish gene, influences memory hours after aversive olfactory learning. How does the radish-dependent phase influence memory performance in different tasks? It is found that the radish memory component does not scale with the stability of several memory traces, indicating a specific recruitment of this component to influence different memories, even within minutes of learning.

  13. Variability in blood and blood component utilization as assessed by an anesthesia information management system.

    Science.gov (United States)

    Frank, Steven M; Savage, Will J; Rothschild, Jim A; Rivers, Richard J; Ness, Paul M; Paul, Sharon L; Ulatowski, John A

    2012-07-01

    Data can be collected for various purposes with anesthesia information management systems. The authors describe methods for using data acquired from an anesthesia information management system to assess intraoperative utilization of blood and blood components. Over an 18-month period, data were collected on 48,086 surgical patients at a tertiary care academic medical center. All data were acquired with an automated anesthesia recordkeeping system. Detailed reports were generated for blood and blood component utilization according to surgical service and surgical procedure, and for individual surgeons and anesthesiologists. Transfusion hemoglobin trigger and target concentrations were compared among surgical services and procedures, and between individual medical providers. For all patients given erythrocytes, the mean transfusion hemoglobin trigger was 8.4 ± 1.5, and the target was 10.2 ± 1.5 g/dl. Variation was significant among surgical services (trigger range: 7.5 ± 1.2-9.5 ± 1.1, P = 0.0001; target range: 9.1 ± 1.2-11.3 ± 1.4 g/dl, P = 0.002), surgeons (trigger range: 7.2 ± 0.7-9.8 ± 1.0, P = 0.001; target range: 8.8 ± 0.9-11.8 ± 1.3 g/dl, P = 0.001), and anesthesiologists (trigger range: 7.2 ± 0.8-9.6 ± 1.2, P = 0.001; target range: 9.0 ± 0.9-11.7 ± 1.3 g/dl, P = 0.0004). The use of erythrocyte salvage, fresh frozen plasma, and platelets varied threefold to fourfold among individual surgeons compared with their peers performing the same surgical procedure. The use of data acquired from an anesthesia information management system allowed a detailed analysis of blood component utilization, which revealed significant variation among surgical services and surgical procedures, and among individual anesthesiologists and surgeons compared with their peers. Incorporating these methods of data acquisition and analysis into a blood management program could reduce unnecessary transfusions, an outcome that may increase patient safety and reduce costs.

  14. Immunological response to quadrivalent HPV vaccine in treatment of recurrent respiratory papillomatosis

    NARCIS (Netherlands)

    Tjon Pian Gi, R.E.A.; San Giorgi, M.R.M.; Pawlita, M.; Michel, A.; van Hemel, B.M.; Schuuring, E.M.D.; van den Heuvel, E.R.; van der Laan, B.F.A.M.; Dikkers, F.G.

    2016-01-01

    Aim of this study was to explore influence of the quadrivalent HPV vaccine (Gardasil®) on the immune status of recurrent respiratory papillomatosis (RRP) patients. In retrospective observational study, six RRP patients who received the quadrivalent HPV vaccine and whose HPV seroreactivity was

  15. The Association Between Gastroesophageal Reflux Disease and Recurrent Respiratory Papillomatosis : A Systematic Review

    NARCIS (Netherlands)

    San Giorgi, Michel R. M.; Helder, Herman M.; Lindeman, Robbert-Jan S.; de Bock, Geertruida H.; Dikkers, Frederik G.

    2016-01-01

    Objectives/Hypothesis: Antireflux therapy is incorporated in many treatment protocols for recurrent respiratory papillomatosis (RRP) because gastroesophageal reflux (GERD) is thought to worsen the disease course of RRP. It is unclear if GERD really aggravates the disease course. The aims of this

  16. First Danish single-institution experience with radical prostatectomy

    DEFF Research Database (Denmark)

    Vrang, Marie-Louise; Røder, Martin Andreas; Vainer, Ben

    2012-01-01

    OBJECTIVE: This study aimed to investigate the impact of positive surgical margins (PSMs), stratified by location and extension, on biochemical outcome after radical retropubic prostatectomy (RRP). MATERIAL AND METHODS: The study included data from 605 consecutive patients treated with RRP for lo...

  17. Melittin suppresses HIF-1α/VEGF expression through inhibition of ERK and mTOR/p70S6K pathway in human cervical carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Jae-Moon Shin

    Full Text Available OBJECTIVE: Melittin (MEL, a major component of bee venom, has been associated with various diseases including arthritis, rheumatism and various cancers. In this study, the anti-angiogenic effects of MEL in CaSki cells that were responsive to the epidermal growth factor (EGF were examined. METHODOLOGY/PRINCIPAL FINDINGS: MEL decreased the EGF-induced hypoxia-inducible factor-1α (HIF-1α protein and significantly regulated angiogenesis and tumor progression. We found that inhibition of the HIF-1α protein level is due to the shortened half-life by MEL. Mechanistically, MEL specifically inhibited the EGF-induced HIF-1α expression by suppressing the phosphorylation of ERK, mTOR and p70S6K. It also blocked the EGF-induced DNA binding activity of HIF-1α and the secretion of the vascular endothelial growth factor (VEGF. Furthermore, the chromatin immunoprecipitation (ChIP assay revealed that MEL reduced the binding of HIF-1α to the VEGF promoter HRE region. The anti-angiogenesis effects of MEL were confirmed through a matrigel plus assay. CONCLUSIONS: MEL specifically suppressed EGF-induced VEGF secretion and new blood vessel formation by inhibiting HIF-1α. These results suggest that MEL may inhibit human cervical cancer progression and angiogenesis by inhibiting HIF-1α and VEGF expression.

  18. The Evolution of Two-Component Systems in Bacteria RevealsDifferent Strategies for Niche Adaptation

    Energy Technology Data Exchange (ETDEWEB)

    Alm, Eric; Huang, Katherine; Arkin, Adam

    2006-09-13

    Two-component systems including histidine protein kinasesrepresent the primary signal transduction paradigm in prokaryoticorganisms. To understand how these systems adapt to allow organisms todetect niche-specific signals, we analyzed the phylogenetic distributionof nearly 5000 histidine protein kinases from 207 sequenced prokaryoticgenomes. We found that many genomes carry a large repertoire of recentlyevolved signaling genes, which may reflect selective pressure to adapt tonew environmental conditions. Both lineage-specific gene family expansionand horizontal gene transfer play major roles in the introduction of newhistidine kinases into genomes; however, there are differences in howthese two evolutionary forces act. Genes imported via horizontal transferare more likely to retain their original functionality as inferred from asimilar complement of signaling domains, while gene family expansionaccompanied by domain shuffling appears to be a major source of novelgenetic diversity. Family expansion is the dominantsource of newhistidine kinase genes in the genomes most enriched in signalingproteins, and detailed analysis reveals that divergence in domainstructure and changes in expression patterns are hallmarks of recentexpansions. Finally, while these two modes of gene acquisition arewidespread across bacterial taxa, there are clear species-specificpreferences for which mode is used.

  19. Antifungal, phytotoxic and insecticidal properties of essential oil isolated from Turkish Origanum acutidens and its three components, carvacrol, thymol and p-cymene.

    Science.gov (United States)

    Kordali, Saban; Cakir, Ahmet; Ozer, Hakan; Cakmakci, Ramazan; Kesdek, Memis; Mete, Ebru

    2008-12-01

    The chemical composition of essential oil isolated by hydrodistillation from the aerial parts of Origanum acutidens was analyzed by GC-MS. Carvacrol (87.0%), p-cymene (2.0%), linalool acetate (1.7%), borneol (1.6%) and beta-caryophyllene (1.3%) were found to be as main constituents. Antifungal, phytotoxic and insecticidal activities of the oil and its aromatic monoterpene constituents, carvacrol, p-cymene and thymol were also determined. The antifungal assays showed that O. acutidens oil, carvacrol and thymol completely inhibited mycelial growth of 17 phytopathogenic fungi and their antifungal effects were higher than commercial fungicide, benomyl. However, p-cymene possessed lower antifungal activity. The oil, carvacrol and thymol completely inhibited the seed germination and seedling growth of Amaranthus retroflexus, Chenopodium album and Rumex crispus and also showed a potent phytotoxic effect against these plants. However, p-cymene did not show any phytotoxic effect. Furthermore, O. acutidens oil showed 68.3% and 36.7% mortality against Sitophilus granarius and Tribolium confusum adults, respectively. The findings of the present study suggest that antifungal and herbicidal properties of the oil can be attributed to its major component, carvacrol, and these agents have a potential to be used as fungicide, herbicide as well as insecticide.

  20. Performance of low pH biofilters treating a paint solvent mixture: Continuous and intermittent loading

    International Nuclear Information System (INIS)

    Qi Bing; Moe, William M.

    2006-01-01

    Two biofilters packed with a reticulated polyurethane foam medium were inoculated with a compost-derived enrichment culture grown under acidic conditions (pH 3.0) and then operated over a period lasting 63 days. Both biofilters were supplied with a humidified gas stream containing a five-component mixture of acetone, methyl ethyl ketone, toluene, ethylbenzene, and p-xylene at a total VOC loading rate 80.3 g m -3 h -1 to simulate treatment of air emissions resulting from manufacture of reformulated paint. One biofilter was operated under continuous loading conditions and the other received intermittent loading with contaminants supplied only 8 h/day. Nutrient solution with pH 3.0 was supplied approximately once per week to provide nitrogen and other nutrients. Data are presented which demonstrate that undefined mixed cultures acclimated at low pH can successfully treat paint solvent mixtures in biofilters. The biofilter receiving continuous loading reached high overall removal efficiency (greater than 90% overall removal) 3 weeks after startup, and performance increased over time reaching overall removal in the range of 97-99% after 50 days. Performance of the intermittently loaded biofilter developed more slowly, requiring 6 weeks to stabilize at an overall removal efficiency in excess of 90%. In both biofilters, ketone components were more rapidly degraded than aromatic components, and removal of aromatic compounds was somewhat unstable even after 2 months of biofilter operation. Scanning electron microscopy (SEM) revealed that fungi dominated the microbial populations in both biofilters

  1. Evaluating cis-2,6-Dimethylpiperidide (cis-DMP) as a Base Component in Lithium-Mediated Zincation Chemistry

    Science.gov (United States)

    Armstrong, David R; Garden, Jennifer A; Kennedy, Alan R; Leenhouts, Sarah M; Mulvey, Robert E; O'Keefe, Philip; O'Hara, Charles T; Steven, Alan

    2013-01-01

    Most recent advances in metallation chemistry have centred on the bulky secondary amide 2,2,6,6-tetramethylpiperidide (TMP) within mixed metal, often ate, compositions. However, the precursor amine TMP(H) is rather expensive so a cheaper substitute would be welcome. Thus this study was aimed towards developing cheaper non-TMP based mixed-metal bases and, as cis-2,6-dimethylpiperidide (cis-DMP) was chosen as the alternative amide, developing cis-DMP zincate chemistry which has received meagre attention compared to that of its methyl-rich counterpart TMP. A new lithium diethylzincate, [(TMEDA)LiZn(cis-DMP)Et2] (TMEDA=N,N,N′,N′-tetramethylethylenediamine) has been synthesised by co-complexation of Li(cis-DMP), Et2Zn and TMEDA, and characterised by NMR (including DOSY) spectroscopy and X-ray crystallography, which revealed a dinuclear contact ion pair arrangement. By using N,N-diisopropylbenzamide as a test aromatic substrate, the deprotonative reactivity of [(TMEDA)LiZn(cis-DMP)Et2] has been probed and contrasted with that of the known but previously uninvestigated di-tert-butylzincate, [(TMEDA)LiZn(cis-DMP)tBu2]. The former was found to be the superior base (for example, producing the ortho-deuteriated product in respective yields of 78 % and 48 % following D2O quenching of zincated benzamide intermediates). An 88 % yield of 2-iodo-N,N-diisopropylbenzamide was obtained on reaction of two equivalents of the diethylzincate with the benzamide followed by iodination. Comparisons are also drawn using 1,1,1,3,3,3-hexamethyldisilazide (HMDS), diisopropylamide and TMP as the amide component in the lithium amide, Et2Zn and TMEDA system. Under certain conditions, the cis-DMP base system was found to give improved results in comparison to HMDS and diisopropylamide (DA), and comparable results to a TMP system. Two novel complexes isolated from reactions of the di-tert-butylzincate and crystallographically characterised, namely the pre-metallation complex [{(iPr)2N

  2. Ab initio investigations of the electronic structures and chemical bonding in LiCo{sub 6}P{sub 4} and Li{sub 2}Co{sub 12}P{sub 7}

    Energy Technology Data Exchange (ETDEWEB)

    Matar, Samir F. [CNRS, ICMCB, UPR 9048, F‐33600 Pessac (France); Université de Bordeaux, ICMCB, UPR 9048, F‐33600 Pessac (France); Al-Alam, Adel; Ouaini, Naïm [Université Saint-Esprit de Kaslik (USEK), Groupe OCM (Optimization et Caractérisation des Matériaux), CSR-USEK, CNRS-L, Jounieh (Lebanon); Pöttgen, Rainer, E-mail: pottgen@uni-muenster.de [Institut für Anorganische und Analytische Chemie, Universität Münster, Corrensstraße 30, D-48149 Münster (Germany)

    2013-06-15

    The electronic structures of the metal-rich phosphides LiCo{sub 6}P{sub 4} and Li{sub 2}Co{sub 12}P{sub 7} were studied by DFT calculations. Both phosphides consist of three-dimensional [Co{sub 6}P{sub 4}] and [Co{sub 12}P{sub 7}] polyanionic networks which leave hexagonal channels for the lithium atoms. COOP data show strong Co–P and Co–Co bonding within the polyanions. The lithium atoms have trigonal prismatic phosphorus coordination. Total energy calculations indicate stability upon de-lithiation towards the Co{sub 6}P{sub 4} and Co{sub 12}P{sub 7} substructures - Graphical abstract: The cobalt–phosphorus networks in LiCo{sub 6}P{sub 4} and Li{sub 2}Co{sub 12}P{sub 7}. - Highlights: • Chemical bonding resolved in the metal-rich phosphides LiCo{sub 6}P{sub 4} and Li{sub 2}Co{sub 12}P{sub 7}. • Strong covalent Co–P bonding character in the [Co{sub 6}P{sub 4}] and [Co{sub 12}P{sub 7}] substructures. • Total energy calculations indicate stability of the de-lithiated substructures.

  3. Probing the KII 3p54p fine structure by photoelectron spectroscopy of laser-excited potassium

    International Nuclear Information System (INIS)

    Meyer, M; Cubaynes, D; Wuilleumier, F J; Heinecke, E; Richter, T; Zimmermann, P; Strakhova, S I; Grum-Grzhimailo, A N

    2006-01-01

    Photoelectron spectra of atomic potassium excited by laser optical pumping into the 3p 6 4p 2 P 1/2 and 2 P 3/2 states are measured with high-energy resolution. The relative intensities of the 3p 5 4p fine-structure lines depend strongly on the initial excitation to one of the 4p spin-orbit components. Similar to the case of sodium, dynamically and quasiforbidden transitions are observed in the photoelectron spectra of potassium. The theoretical predictions of the generalized geometrical model are in excellent agreement with the experimental data. (letter to the editor)

  4. Comparative Genomics of Methanopyrus sp. SNP6 and KOL6 Revealing Genomic Regions of Plasticity Implicated in Extremely Thermophilic Profiles

    Directory of Open Access Journals (Sweden)

    Zhiliang Yu

    2017-07-01

    Full Text Available Methanopyrus spp. are usually isolated from harsh niches, such as high osmotic pressure and extreme temperature. However, the molecular mechanisms for their environmental adaption are poorly understood. Archaeal species is commonly considered as primitive organism. The evolutional placement of archaea is a fundamental and intriguing scientific question. We sequenced the genomes of Methanopyrus strains SNP6 and KOL6 isolated from the Atlantic and Iceland, respectively. Comparative genomic analysis revealed genetic diversity and instability implicated in niche adaption, including a number of transporter- and integrase/transposase-related genes. Pan-genome analysis also defined the gene pool of Methanopyrus spp., in addition of ~120-Kb genomic region of plasticity impacting cognate genomic architecture. We believe that Methanopyrus genomics could facilitate efficient investigation/recognition of archaeal phylogenetic diverse patterns, as well as improve understanding of biological roles and significance of these versatile microbes.

  5. D-Glucosamine inhibits proliferation of human cancer cells through inhibition of p70S6K

    International Nuclear Information System (INIS)

    Oh, Hyun-Ji; Lee, Jason S.; Song, Dae-Kyu; Shin, Dong-Hoon; Jang, Byeong-Churl; Suh, Seong-Il; Park, Jong-Wook; Suh, Min-Ho; Baek, Won-Ki

    2007-01-01

    Although D-glucosamine has been reported as an inhibitor of tumor growth both in vivo and in vitro, the mechanism for the anticancer effect of D-glucosamine is still unclear. Since there are several reports suggesting D-glucosamine inhibits protein synthesis, we examined whether D-glucosamine affects p70S6 K activity, an important signaling molecule involved in protein translation. In the present study, we found D-glucosamine inhibited the activity of p70S6K and the proliferation of DU145 prostate cancer cells and MDA-MB-231 breast cancer cells. D-Glucosamine decreased phosphorylation of p70S6K, and its downstream substrates RPS6, and eIF-4B, but not mTOR and 4EBP1 in DU145 cells, suggesting that D-glucosamine induced inhibition of p70S6K is not through the inhibition of mTOR. In addition, D-glucosamine enhanced the growth inhibitory effects of rapamycin, a specific inhibitor of mTOR. These findings suggest that D-glucosamine can inhibit growth of cancer cells through dephosphorylation of p70S6K

  6. Rare human papillomavirus 16 E6 variants reveal significant oncogenic potential

    Directory of Open Access Journals (Sweden)

    Tommasino Massimo

    2011-06-01

    Full Text Available Abstract The aim of this study was to determine whether low prevalence human papillomavirus (HPV 16 E6 variants differ from high prevalence types in their functional abilities. We evaluated functions relevant to carcinogenesis for the rarely-detected European variants R8Q, R10G and R48W as compared to the commonly detected L83V. Human immortalized keratinocytes (NIKS stably transduced with the E6 variants were used in most functional assays. Low and high prevalence E6 variants displayed similar abilities in abrogation of growth arrest and inhibition of p53 elevation induced by actinomycin D. Differences were detected in the abilities to dysregulate stratification and differentiation of NIKS in organotypic raft cultures, modulate detachment induced apoptosis (anoikis and hyperactivate Wnt signaling. No distinctive phenotype could be assigned to include all rare variants. Like L83V, raft cultures derived from variants R10G and R48W similarly induced hyperplasia and aberrantly expressed keratin 5 in the suprabasal compartment with significantly lower expression of keratin 10. Unlike L83V, both variants, and particularly R48W, induced increased levels of anoikis upon suspension in semisolid medium. R8Q induced a unique phenotype characterized by thin organotypic raft cultures, low expression of keratin 10, and high expression of keratins 5 and 14 throughout all raft layers. Interestingly, in a reporter based assay R8Q exhibited a higher ability to augment TCF/β-catenin transcription. The data suggests that differences in E6 variant prevalence in cervical carcinoma may not be related to the carcinogenic potential of the E6 protein.

  7. One-dimensional zinc selenophosphates: A{sub 2}ZnP{sub 2}Se{sub 6} (A = K, Rb, Cs)

    Energy Technology Data Exchange (ETDEWEB)

    Haynes, Alyssa S.; Lee, Katherine; Kanatzidis, Mercouri G. [Department of Chemistry, Northwestern University, Evanston, IL (United States)

    2016-09-15

    The new compounds A{sub 2}ZnP{sub 2}Se{sub 6} (A = K, Rb, Cs) were synthesized via molten salt flux syntheses. The crystals feature one-dimensional {sup 1}/{sub ∞}[ZnP{sub 2}Se{sub 6}]{sup 2-} chains charge balanced by alkali metal ions between the chains. K{sub 2}ZnP{sub 2}Se{sub 6} crystallizes in the monoclinic space group P2{sub 1}/c; cell parameters a = 12.537(3) Aa, b = 7.2742(14) Aa, c = 14.164(3) Aa, β = 109.63(3) , Z = 4, and V = 1216.7(4) Aa{sup 3}. Rb{sub 2}ZnP{sub 2}Se{sub 6} and Cs{sub 2}ZnP{sub 2}Se{sub 6} are isotypic, crystallizing in the triclinic space group P anti 1. Rb{sub 2}ZnP{sub 2}Se{sub 6} has cell parameters of a = 7.4944(15) Aa, b = 7.6013(15) Aa, c = 12.729(3) Aa, α = 96.57(3) , β = 105.52(3) , γ = 110.54(3) , Z = 2, and V = 636.6(2) Aa{sup 3}. Cs{sub 2}ZnP{sub 2}Se{sub 6} has cell parameters of a = 7.6543(6) Aa, b = 7.7006(6) Aa, c = 12.7373(11) Aa, α = 97.007(7) , β = 104.335(7) , γ = 109.241(6) , Z = 2, and V = 669.54(10) Aa{sup 3}. (Copyright copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. Revealing charge carrier dynamics in squaraine:[6, 6]-phenyl-C 71-butyric acid methyl ester based organic solar cells

    Science.gov (United States)

    Rana, Aniket; Sharma, Chhavi; Prabhu, Deepak D.; Kumar, Mahesh; Karuvath, Yoosaf; Das, Suresh; Chand, Suresh; Singh, Rajiv K.

    2018-04-01

    Ultrafast charge carrier dynamics as well as the generation of polaron pair in squaraine (SQ) and squaraine:[6,6]-phenyl-C 71-butyric acid methyl ester (SQ:PCBM71) have been studied using ultrafast transient absorption spectroscopy (UTAS). The current study reveals that the pure SQ exhibits the creation of singlet and triplet states; however, incorporation of PCBM71 in SQ results in the formation of polaron pairs with ˜550ps lifetime, which in turn leads to the creation of free electrons in the device. We show that the considerable increment in monomolecular and bimolecular recombination in SQ:PCBM71 compared to pure SQ which describes the interfacial compatibility of SQ and PCBMC71 molecules. The present work not only provides the information about the carrier generation in SQ and SQ:PCBM71 but also gives the facts relating to the effect of PCBM71 mixing into the SQ which is very significant because the SQ has donor-acceptor-donor (D-A-D) structure and mixing one more acceptor can introduce more complex recombinations in the blend. These findings have been complimented by the charge transport study in the device using impedance spectroscopy. The various important transport parameters are transit time (τt), diffusion constant (Dn), global mobility (μ) and carrier lifetime (τr). The values of these parameters are 26.38 μs, 4.64x10-6 cm2s-1, 6.12x10-6 cm2V-1s-1 and 399 μs, respectively. To the best of our knowledge such study related to SQ is not present in the literature comprehensively.

  9. Determination of the human cytochrome P450 monooxygenase catalyzing the enantioselective oxidation of 2,2',3,5',6-pentachlorobiphenyl (PCB 95) and 2,2',3,4,4',5',6-heptachlorobiphenyl (PCB 183).

    Science.gov (United States)

    Nagayoshi, Haruna; Kakimoto, Kensaku; Konishi, Yoshimasa; Kajimura, Keiji; Nakano, Takeshi

    2017-10-17

    2,2',3,5',6-Pentachlorobiphenyl (PCB 95) and 2,2',3,4,4',5',6-heptachlorobiphenyl (PCB 183) possess axial chirality and form the aS and aR enantiomers. The enantiomers of these congeners have been reported to accumulate in the human body enantioselectively via unknown mechanisms. In this study, we determined the cytochrome P450 (CYP) monooxygenase responsible for the enantioselective oxidization of PCB 95 and PCB 183, using a recombinant human CYP monooxygenase. We evaluated 13 CYP monooxygenases, namely CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2, CYP3A4, CYP3A5, CYP4F2, and aromatase (CYP19), and revealed that CYP2A6 preferably oxidizes aS-PCB 95 enantioselectively; however, it did not oxidize PCB 183. The enantiomer composition was elevated from 0.5 (racemate) to 0.54. In addition, following incubation with CYP2A6, the enantiomer fraction (EF) of PCB 95 demonstrated a time-dependent increase.

  10. Mechanism of the alkali degradation of (6-4) photoproduct-containing DNA.

    Science.gov (United States)

    Arichi, Norihito; Inase, Aki; Eto, Sachise; Mizukoshi, Toshimi; Yamamoto, Junpei; Iwai, Shigenori

    2012-03-21

    The (6-4) photoproduct is one of the major damaged bases produced by ultraviolet light in DNA. This lesion is known to be alkali-labile, and strand breaks occur at its sites when UV-irradiated DNA is treated with hot alkali. We have analyzed the product obtained by the alkali treatment of a dinucleoside monophosphate containing the (6-4) photoproduct, by HPLC, NMR spectroscopy, and mass spectrometry. We previously found that the N3-C4 bond of the 5' component was hydrolyzed by a mild alkali treatment, and the present study revealed that the following reaction was the hydrolysis of the glycosidic bond at the 3' component. The sugar moiety of this component was lost, even when a 3'-flanking nucleotide was not present. Glycosidic bond hydrolysis was also observed for a dimer and a trimer containing 5-methyl-2-pyrimidinone, which was used as an analog of the 3' component of the (6-4) photoproduct, and its mechanism was elucidated. Finally, the alkali treatment of a tetramer, d(GT(6-4)TC), yielded 2'-deoxycytidine 5'-monophosphate, while 2'-deoxyguanosine 3'-monophosphate was not detected. This result demonstrated the hydrolysis of the glycosidic bond at the 3' component of the (6-4) photoproduct and the subsequent strand break by β-elimination. It was also shown that the glycosidic bond at the 3' component of the Dewar valence isomer was more alkali-labile than that of the (6-4) photoproduct.

  11. Implications of the Primary Cilium in Cellular Signaling and Brain Development

    DEFF Research Database (Denmark)

    Lindbæk, Louise

    neurogenesis. In addition, analysis of patient dermal fibroblasts show, that RRP7A localizes to nucleoli, centrosomes, and cilia, and that patient cells carrying a single amino acid substitution in RRP7A display reduced nucleoli localization. Moreover, patient-derived fibroblasts display defects in ribosomal...

  12. Immunological response to quadrivalent HPV vaccine in treatment of recurrent respiratory papillomatosis

    NARCIS (Netherlands)

    Tjon Pian Gi, Robin E. A.; San Giorgi, Michel R. M.; Pawlita, Michael; Michel, Angelika; van Hemel, Bettien M.; Schuuring, Ed M. D.; van den Heuvel, Edwin R.; van der Laan, Bernard F. A. M.; Dikkers, Frederik G.

    2016-01-01

    Aim of this study was to explore influence of the quadrivalent HPV vaccine (Gardasil(A (R))) on the immune status of recurrent respiratory papillomatosis (RRP) patients. In retrospective observational study, six RRP patients who received the quadrivalent HPV vaccine and whose HPV seroreactivity was

  13. Complete physical mapping of IL6 reveals a new marker associated with chronic periodontitis.

    Science.gov (United States)

    Farhat, S B; de Souza, C M; Braosi, A P R; Kim, S H; Tramontina, V A; Papalexiou, V; Olandoski, M; Mira, M T; Luczyszyn, S M; Trevilatto, P C

    2017-04-01

    Interleukin-6 (IL-6) is a powerful stimulator of osteoclast differentiation and bone resorption. Production of IL-6 is modulated by polymorphisms, and higher levels of this cytokine are found locally in patients with chronic periodontitis. In this study we performed a modern approach - Complete physical mapping of the IL6 gene - to identify the polymorphisms associated with chronic periodontitis in a southern Brazilian population sample. One-hundred and nine individuals of both genders (mean age: 41.5 ± 8.5 years) were divided into a study group (56 participants with periodontitis) and a control group (53 individuals without periodontitis). After collection and purification of DNA, nine tag single nucleotide polymorphisms (SNPs; rs1524107, rs2069835, rs2069837, rs2069838, rs2069840, rs2069842, rs2069843, rs2069845 and rs2069849) covering the entire gene were selected according to the information available on the International HapMap Project website and evaluated using real-time PCR. Differences in the distribution of the following parameters were statistically significant between study and control groups: number of teeth (p = 0.030); probing depth (p chronic periodontitis in a Brazilian population in the presence of clinical variables, such as visible plaque, dentist visit frequency and dental floss use, and was suggested for the first time as a marker of susceptibility to chronic periodontitis. Complete physical mapping of IL6 (using tag SNPs) was carried out for the first time, unveiling allele G of polymorphism rs2069837 (located in the second intron of IL6) as a suggestive marker of protection against chronic periodontitis in a Brazilian population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. P2Y6 receptor potentiates pro-inflammatory responses in macrophages and exhibits differential roles in atherosclerotic lesion development.

    Directory of Open Access Journals (Sweden)

    Ricardo A Garcia

    Full Text Available BACKGROUND: P2Y(6, a purinergic receptor for UDP, is enriched in atherosclerotic lesions and is implicated in pro-inflammatory responses of key vascular cell types and macrophages. Evidence for its involvement in atherogenesis, however, has been lacking. Here we use cell-based studies and three murine models of atherogenesis to evaluate the impact of P2Y(6 deficiency on atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: Cell-based studies in 1321N1 astrocytoma cells, which lack functional P2Y(6 receptors, showed that exogenous expression of P2Y(6 induces a robust, receptor- and agonist-dependent secretion of inflammatory mediators IL-8, IL-6, MCP-1 and GRO1. P2Y(6-mediated inflammatory responses were also observed, albeit to a lesser extent, in macrophages endogenously expressing P2Y(6 and in acute peritonitis models of inflammation. To evaluate the role of P2Y(6 in atherosclerotic lesion development, we used P2Y(6-deficient mice in three mouse models of atherosclerosis. A 43% reduction in aortic arch plaque was observed in high fat-fed LDLR knockout mice lacking P2Y(6 receptors in bone marrow-derived cells. In contrast, no effect on lesion development was observed in fat-fed whole body P2Y(6xLDLR double knockout mice. Interestingly, in a model of enhanced vascular inflammation using angiotensin II, P2Y(6 deficiency enhanced formation of aneurysms and exhibited a trend towards increased atherosclerosis in the aorta of LDLR knockout mice. CONCLUSIONS: P2Y(6 receptor augments pro-inflammatory responses in macrophages and exhibits a pro-atherogenic role in hematopoietic cells. However, the overall impact of whole body P2Y(6 deficiency on atherosclerosis appears to be modest and could reflect additional roles of P2Y(6 in vascular disease pathophysiologies, such as aneurysm formation.

  15. Architecture of the Vibrio cholerae toxin-coregulated pilus machine revealed by electron cryotomography

    DEFF Research Database (Denmark)

    Chang, Yi Wei; Kjær, Andreas; Ortega, Davi R.

    2017-01-01

    ,2. T4aP are more widespread and are involved in cell motility 3, DNA transfer 4, host predation 5 and electron transfer 6. T4bP are less prevalent and are mainly found in enteropathogenic bacteria, where they play key roles in host colonization 7. Following similar work on T4aP machines 8,9, here we...... sequence homology to components of the previously analysed Myxococcus xanthus T4aP machine (T4aPM), we find that their structures are nevertheless remarkably similar. Based on homologies with components of the M. xanthus T4aPM and additional reconstructions of TCPM mutants in which the non...

  16. Nano crystalline ZnO catalyzed one pot three-component synthesis of 7-alkyl-6H,7H- naphtho[1',2':5,6]pyrano[3,2-c] chromen-6-ones under solvent-free conditions

    Directory of Open Access Journals (Sweden)

    M. J. Piltan

    2016-08-01

    Full Text Available In the present paper, an efficient one-pot synthesis of 7-alkyl-6H,7H-naphtho[1',2':5,6]pyrano[3,2-c]chromen-6-ones is described by three-component reaction of β-naphthol, aromatic aldehydes and 4-hydroxycoumarin using ZnO nanoparticles under solvent-free conditions. The present method provides a novel and efficient procedure for the synthesis of chromene derivatives with some advantageous such as short reaction times, easy workup, high yields, wide range of products, reusability of the catalyst, little catalyst loading and green conditions in the presence of ZnO nanoparticles (7 mol% at 110 ºC.

  17. The supplementation of low-P diets with microbial 6-phytase expressed in Aspergillus oryzae increases P and Ca digestibility in growing pigs.

    Science.gov (United States)

    Torrallardona, D; Salvadó, R; Broz, J

    2012-12-01

    A trial was conducted to evaluate the dose response of a novel microbial 6-phytase expressed in Aspergillus oryzae (Ronozyme HiPhos; DSM Nutritional Products, Basel, Switzerland) in pigs. Forty-eight individually housed pigs (Landrace × Pietrain; 52 kg BW; 24 males and 24 females) were distributed among 6 experimental treatments consisting of a low-P diet (3.5 g P/kg; 1.1 g digestible P/kg), which was supplemented with 500, 1000, 2000, or 4000 units of phytase activity/kg, and a standard-P diet (4.5 g P/kg; 1.8 g digestible P/kg) that was supplemented with CaHPO(4). After 17 d, fresh feces were sampled from all pigs and the apparent total tract digestibility of DM, OM, ash, P, and Ca was measured using TiO(2) as indigestible marker. Blood samples were also obtained from each pig and serum was analyzed for P and Ca concentrations. The nonsupplemented low-P diet increased Ca and reduced P blood serum concentrations (P Phytase supplementation of the low-P diet reduced Ca (from 10.8 to 9.9 mg/dL; linear, P Phytase improved the total tract digestibility of P (from 29.0 to 62.3%; linear and quadratic, P phytase tested improves the apparent total tract digestibility of P in growing pigs and reduces P excretion in feces in a dose-dependent manner.

  18. The cytochrome P450 CYP6P4 is responsible for the high pyrethroid resistance in knockdown resistance-free Anopheles arabiensis.

    Science.gov (United States)

    Ibrahim, Sulaiman S; Riveron, Jacob M; Stott, Robert; Irving, Helen; Wondji, Charles S

    2016-01-01

    Pyrethroid insecticides are the front line vector control tools used in bed nets to reduce malaria transmission and its burden. However, resistance in major vectors such as Anopheles arabiensis is posing a serious challenge to the success of malaria control. Herein, we elucidated the molecular and biochemical basis of pyrethroid resistance in a knockdown resistance-free Anopheles arabiensis population from Chad, Central Africa. Using heterologous expression of P450s in Escherichia coli coupled with metabolism assays we established that the over-expressed P450 CYP6P4, located in the major pyrethroid resistance (rp1) quantitative trait locus (QTL), is responsible for resistance to Type I and Type II pyrethroid insecticides, with the exception of deltamethrin, in correlation with field resistance profile. However, CYP6P4 exhibited no metabolic activity towards non-pyrethroid insecticides, including DDT, bendiocarb, propoxur and malathion. Combining fluorescent probes inhibition assays with molecular docking simulation, we established that CYP6P4 can bind deltamethrin but cannot metabolise it. This is possibly due to steric hindrance because of the large vdW radius of bromine atoms of the dihalovinyl group of deltamethrin which docks into the heme catalytic centre. The establishment of CYP6P4 as a partial pyrethroid resistance gene explained the observed field resistance to permethrin, and its inability to metabolise deltamethrin probably explained the high mortality from deltamethrin exposure in the field populations of this Sudano-Sahelian An. arabiensis. These findings describe the heterogeneity in resistance towards insecticides, even from the same class, highlighting the need to thoroughly understand the molecular basis of resistance before implementing resistance management/control tools. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Iodine-123-labelled serum amyloid P component scintigraphy in amyloidosis

    International Nuclear Information System (INIS)

    Saile, R.; Deveaux, M.; Marchandise, X.; Duquesnoy, B.

    1993-01-01

    This study describes the results of scintigraphy with iodine-123-labelled serum amyloid P component (SAP) as a means of establishing the distribution of organ involvement in amyloidosis. The significance of 123 I-SAP scans obtained in 15 patients with biopsy-proven AA or AL amyloidosis is discussed. Biopsy-proven amyloidosis was typically confirmed by scintigraphy, though such confirmation was not obtained in the kidneys in six patients with histological proof of extensive renal amyloid deposition. This lack of uptake may have been due to the accumulation of a major part of the 123 I-SAP in the spleen and/or liver. Twenty-four hour whole-body retention of 123 I-SAP was higher in patients with amyloidosis than in controls. Twenty-four hour tracer accumulation of the radioactivity in the extravascular compartment was notably greater in patients than in controls and appeared to be a good diagnostic criterion. We conclude that 123 I-SAP scintigraphy may be helpful for the evaluation of organ involvement not only in patients with biopsy-proven amyloidosis but also when a biopsy cannot be performed or when a strong suspicion of amyloidosis exists in spite of repeated negative biopsises. (orig.)

  20. Salinity-induced inhibition of growth in the aquatic pteridophyte Azolla microphylla primarily involves inhibition of photosynthetic components and signaling molecules as revealed by proteome analysis.

    Science.gov (United States)

    Thagela, Preeti; Yadav, Ravindra Kumar; Mishra, Vagish; Dahuja, Anil; Ahmad, Altaf; Singh, Pawan Kumar; Tiwari, Budhi Sagar; Abraham, Gerard

    2017-01-01

    Salinity stress causes adverse physiological and biochemical changes in the growth and productivity of a plant. Azolla, a symbiotic pteridophyte and potent candidate for biofertilizer due to its nitrogen fixation ability, shows reduced growth and nitrogen fixation during saline stress. To better understand regulatory components involved in salinity-induced physiological changes, in the present study, Azolla microphylla plants were exposed to NaCl (6.74 and 8.61 ds/m) and growth, photochemical reactions of photosynthesis, ion accumulation, and changes in cellular proteome were studied. Maximum dry weight was accumulated in control and untreated plant while a substantial decrease in dry weight was observed in the plants exposed to salinity. Exposure of the organism to different concentrations of salt in hydroponic conditions resulted in differential level of Na + and K + ion accumulation. Comparative analysis of salinity-induced proteome changes in A. microphylla revealed 58 salt responsive proteins which were differentially expressed during the salt exposure. Moreover, 42 % spots among differentially expressed proteins were involved in different signaling events. The identified proteins are involved in photosynthesis, energy metabolism, amino acid biosynthesis, protein synthesis, and defense. Downregulation of these key metabolic proteins appears to inhibit the growth of A. microphylla in response to salinity. Altogether, the study revealed that in Azolla, increased salinity primarily affected signaling and photosynthesis that in turn leads to reduced biomass.

  1. Detecting terrestrial nutrient limitation: a global meta-analysis of foliar nutrient concentrations after fertilization

    Directory of Open Access Journals (Sweden)

    Rebecca eOstertag

    2016-03-01

    Full Text Available Examining foliar nutrient concentrations after fertilization provides an alternative method for detecting nutrient limitation of ecosystems, which is logistically simpler to measure than biomass change. We present a meta-analysis of response ratios of foliar nitrogen and phosphorus (RRN, RRP after addition of fertilizer of nitrogen (N, phosphorus (P, or the two elements in combination, in relation to climate, ecosystem type, life form, family, and methodological factors. Results support other meta-analyses using biomass, and demonstrate there is strong evidence for nutrient limitation in natural communities. However, because N fertilization experiments greatly outnumber P fertilization trials, it is difficult to discern the absolute importance of N vs. P vs. co-limitation across ecosystems. Despite these caveats, it is striking that results did not follow conventional wisdom that temperate ecosystems are N-limited and tropical ones are P-limited. In addition, the use of ratios of N-to-P rather than response ratios also are a useful index of nutrient limitation, but due to large overlap in values, there are unlikely to be universal cutoff values for delimiting N vs. P limitation. Differences in RRN and RRP were most significant across ecosystem types, plant families, life forms, and between competitive environments, but not across climatic variables.

  2. Visualization of the Serratia Type VI Secretion System Reveals Unprovoked Attacks and Dynamic Assembly

    Directory of Open Access Journals (Sweden)

    Amy J. Gerc

    2015-09-01

    Full Text Available The Type VI secretion system (T6SS is a bacterial nanomachine that fires toxic proteins into target cells. Deployment of the T6SS represents an efficient and widespread means by which bacteria attack competitors or interact with host organisms and may be triggered by contact from an attacking neighbor cell as a defensive strategy. Here, we use the opportunist pathogen Serratia marcescens and functional fluorescent fusions of key components of the T6SS to observe different subassemblies of the machinery simultaneously and on multiple timescales in vivo. We report that the localization and dynamic behavior of each of the components examined is distinct, revealing a multi-stage and dynamic assembly process for the T6SS machinery. We also show that the T6SS can assemble and fire without needing a cell contact trigger, defining an aggressive strategy that broadens target range and suggesting that activation of the T6SS is tailored to survival in specific niches.

  3. Visualization of the Serratia Type VI Secretion System Reveals Unprovoked Attacks and Dynamic Assembly

    Science.gov (United States)

    Gerc, Amy J.; Diepold, Andreas; Trunk, Katharina; Porter, Michael; Rickman, Colin; Armitage, Judith P.; Stanley-Wall, Nicola R.; Coulthurst, Sarah J.

    2015-01-01

    Summary The Type VI secretion system (T6SS) is a bacterial nanomachine that fires toxic proteins into target cells. Deployment of the T6SS represents an efficient and widespread means by which bacteria attack competitors or interact with host organisms and may be triggered by contact from an attacking neighbor cell as a defensive strategy. Here, we use the opportunist pathogen Serratia marcescens and functional fluorescent fusions of key components of the T6SS to observe different subassemblies of the machinery simultaneously and on multiple timescales in vivo. We report that the localization and dynamic behavior of each of the components examined is distinct, revealing a multi-stage and dynamic assembly process for the T6SS machinery. We also show that the T6SS can assemble and fire without needing a cell contact trigger, defining an aggressive strategy that broadens target range and suggesting that activation of the T6SS is tailored to survival in specific niches. PMID:26387948

  4. Diels-Alders adducts of C-60 and esters of 3-(1-indenyl)-propionic acid : alternatives for [60]PCBM in polymer:fullerene solar cells

    NARCIS (Netherlands)

    Sieval, Alexander B.; Treat, Neil D.; Rozema, Desiree; Hummelen, Jan C.; Stingelin, Natalie

    2015-01-01

    A series of new, easily synthesized C-60-fullerene derivatives is introduced that allow for optimization of the interactions between rr-P3HT and the fullerene by systematic variation of the size of the ester group. Two compounds gave overall cell efficiencies of 4.8%, clearly outperforming [60]PCBM

  5. Revealing spatio-spectral electroencephalographic dynamics of musical mode and tempo perception by independent component analysis.

    Science.gov (United States)

    Lin, Yuan-Pin; Duann, Jeng-Ren; Feng, Wenfeng; Chen, Jyh-Horng; Jung, Tzyy-Ping

    2014-02-28

    Music conveys emotion by manipulating musical structures, particularly musical mode- and tempo-impact. The neural correlates of musical mode and tempo perception revealed by electroencephalography (EEG) have not been adequately addressed in the literature. This study used independent component analysis (ICA) to systematically assess spatio-spectral EEG dynamics associated with the changes of musical mode and tempo. Empirical results showed that music with major mode augmented delta-band activity over the right sensorimotor cortex, suppressed theta activity over the superior parietal cortex, and moderately suppressed beta activity over the medial frontal cortex, compared to minor-mode music, whereas fast-tempo music engaged significant alpha suppression over the right sensorimotor cortex. The resultant EEG brain sources were comparable with previous studies obtained by other neuroimaging modalities, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). In conjunction with advanced dry and mobile EEG technology, the EEG results might facilitate the translation from laboratory-oriented research to real-life applications for music therapy, training and entertainment in naturalistic environments.

  6. Quality and readability assessment of websites related to recurrent respiratory papillomatosis.

    Science.gov (United States)

    San Giorgi, Michel R M; de Groot, Olivier S D; Dikkers, Frederik G

    2017-10-01

    Recurrent respiratory papillomatosis (RRP) is a rare disease for which a limited number of information sources for patients exist. The role of the Internet in the patient-physician relationship is increasing. More and more patients search for online health information, which should be of good quality and easy readable. The study aim was to investigate the quality and readability of English online health information about RRP. Quality and readability assessment of online information. Relevant information was collected using three different search engines and seven different search terms. Quality was assessed with the DISCERN instrument. The Flesch Reading Ease Score (FRES) and average grade level (AGL) were determined to measure readability of the English websites. Fifty-one English websites were included. The mean DISCERN score of the websites is 28.1 ± 9.7 (poor quality); the mean FRES is 41.3 ± 14.9 (difficult to read); and the mean AGL is 12.6 ± 2.3. The quality and readability of English websites about RRP is alarmingly poor. NA. Laryngoscope, 127:2293-2297, 2017. © 2017 The Authors The Laryngoscope published by Wiley Periodicals, Inc. on behalf of American Laryngological, Rhinological and Otological Society Inc, “The Triological Society” and American Laryngological Association (ALA).

  7. Electroencephalographic dynamics of musical emotion perception revealed by independent spectral components.

    Science.gov (United States)

    Lin, Yuan-Pin; Duann, Jeng-Ren; Chen, Jyh-Horng; Jung, Tzyy-Ping

    2010-04-21

    This study explores the electroencephalographic (EEG) correlates of emotional experience during music listening. Independent component analysis and analysis of variance were used to separate statistically independent spectral changes of the EEG in response to music-induced emotional processes. An independent brain process with equivalent dipole located in the fronto-central region exhibited distinct δ-band and θ-band power changes associated with self-reported emotional states. Specifically, the emotional valence was associated with δ-power decreases and θ-power increases in the frontal-central area, whereas the emotional arousal was accompanied by increases in both δ and θ powers. The resultant emotion-related component activations that were less interfered by the activities from other brain processes complement previous EEG studies of emotion perception to music.

  8. IL-3 Maintains Activation of the p90S6K/RPS6 Pathway and Increases Translation in Human Eosinophils.

    Science.gov (United States)

    Esnault, Stephane; Kelly, Elizabeth A B; Shen, Zhong-Jian; Johansson, Mats W; Malter, James S; Jarjour, Nizar N

    2015-09-15

    IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines, such as IL-5, IL-3, and GM-CSF, are typically present in atopic diseases, including allergic asthma. As a result of the functional redundancy of these three cytokines on eosinophils and the loss of IL-5R on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these three cytokines signal through a common β-chain receptor but yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce the production of proteins, such as semaphorin-7A, without affecting mRNA levels suggests a unique influence of IL-3 on translation. The purpose of this study was to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared with IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF, or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein S6 (RPS6) and the upstream kinase 90-kDa ribosomal S6 kinase (p90S6K). Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL-3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared with circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM-CSF, and IL-5. These observations identify IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions. Copyright © 2015 by The American Association of Immunologists, Inc.

  9. Effect of NaCrSi2O6 component on Lindsley's pyroxene thermometer: An evaluation based on strongly metamorphosed LL chondrites

    Science.gov (United States)

    Nakamuta, Y.; Urata, K.; Shibata, Y.; Kuwahara, Y.

    2017-03-01

    In Lindsley's thermometry, a revised sequence of calculation of components is proposed for clinopyroxene, in which kosmochlor component is added. Temperatures obtained for the components calculated by the revised method are about 50 °C lower than those obtained for the components calculated by the Lindsley's original method and agree well with temperatures obtained from orthopyroxenes. Ca-partitioning between clino- and orthopyroxenes is then thought to be equilibrated in types 5 to 7 ordinary chondrites. The temperatures for Tuxtuac (LL5), Dhurmsala (LL6), NWA 2092 (LL6/7), and Dho 011 (LL7) are 767-793°, 818-835°, 872-892°, and 917-936°C, respectively, suggesting that chondrites of higher petrographic types show higher equilibrium temperatures of pyroxenes. The regression equations which relate temperature and Wo and Fs contents in the temperature-contoured pyroxene quadrilateral of 1 atm of Lindsley (1983) are also determined by the least squares method. It is possible to reproduce temperatures with an error less than 20 °C (2SE) using the regression equations.

  10. Interaction of actinide ions with [NaP5W30O110]14- and [P2W18O62]6-

    International Nuclear Information System (INIS)

    Choppin, G.R.; Wall, D.E.

    2003-01-01

    Stability constants (log β 101 ) of Th 4+ , UO 2 2+ , NpO 2 + and Am 3+ with [NaP 5 W 30 O 110 ] 14- were determined by solvent extraction (μ = 0.1M NaCl) and found to be 6.18 ± 0.07, 3.80 ± 0.06, 2.98 ± 0.04, and 5.85 ± 0.05, respectively. The order of stability constants: Th 4+ > Am 3+ > UO 2 2+ > NpO 2 + is due to electrostatic repulsion between the actinyl oxygens and oxygens on the polyoxometalate surface. The order of stability constants for metal complexes with [P 2 W 18 O 62 ] 6- is Th 4+ > UO 2 2+ > Eu 3+ >NpO 2 + because the steric repulsion between actinyl oxygens and oxygens on polyoxometalate are less important. Enthalpies of complexation were measured by calorimetric titration of Th 4+ , UO 2 2+ , Nd 3+ with [NaP 5 W 30 O 110 ] 14- and [P 2 W 18 O 62 ] 6- . The results indicate that the conformation and charge distribution of the microscopic surface structures are important factors in the formation of pseudocolloids. (author)

  11. Initiation of proteolysis of yeast fructose-1,6-bisphosphatase by pH-control of adenylate cyclase

    International Nuclear Information System (INIS)

    Holzer, H.; Purwin, C.; Pohlig, G.; Scheffers, W.A.; Nicolay, K.

    1986-01-01

    Addition of fermentable sugars or uncouplers such as CCCP to resting yeast cells grown on glucose initiates phosphorylation of fructose-1,6-bisphosphatase (FBPase). There is good evidence that phosphorylation marks FBPase for proteolytic degradation. 31 P-NMR measurements of the cytosolic pH of yeast cells demonstrated a decrease of the cytosolic pH from 7.0 to 6.5 after addition of glucose or CCCP to starved yeast. Activity of adenylate cyclase in permeabilized yeast cells increases 2-3-fold when the pH is lowered from 7.0 to 6.5. It is concluded that pH controlled activation of adenylate cyclase causes the previously described increase in cyclic AMP which leads to phosphorylation of FBPase and finally to proteolysis of FBPase

  12. Negative “gossip” stimuli modulate left-lateralized P1 component while viewing neutral faces

    DEFF Research Database (Denmark)

    Weed, Ethan; Allen, Micah Galen; Gramm, Daniel

    , Anderson et al. (2011) showed that short “gossip” phrases modulated the length of time faces remained perceptually dominant. However, binocular rivalry is measured by self-report. We used EEG to investigate the timing of gossip’s early effect on face perception. Gossip stimuli were those used by Anderson...... et al. (2011), translated to Danish. Neutral faces were taken from the PUT database (Kasiński et al., 2008). Participants (n=30) viewed each face together with the gossip stimuli a total of six times. Following this encoding period, 32 channels of EEG were recorded while participants viewed the faces...... mixed with unfamiliar faces, and performed a distracter task. A post-test checked participants’ memory of the individual faces. We hypothesized that negative gossip would modulate the face-sensitive N170 component at electrodes P7 and P8. No differences were observed in the N170, and no memory effect...

  13. Expression and subcellular localization of p70S6 kinase under heart failure

    Directory of Open Access Journals (Sweden)

    Usenko V. S.

    2010-11-01

    Full Text Available The PI3K/PDK/Akt/mTOR/p70S6K signaling pathway is primary associated with the activation of insulin receptors and is important for cardiomyocytes survival. p70S6K is a key regulator of the speed and efficiency of protein biosynthesis within the cell. Recently the pro-apoptotic protein BAD has been identified as a new target for р70S6K1. BAD is inactivated in normal cardiomyocytes by р70S6K1 phosphorylation which prevents the cardiomyocytes apoptosis. Aim. To study possible changes in р70S6K1 expression and/or cellular localization at heart failure progression – in DCM- affected human myocardia and murine hearts with experimental DCM-like pathology. Methods. Western-blot analysis and immunohystochemistry. Results. The substantial decrease in р70S6K1 level was observed at the final stage of pathology progression and in the dynamics of DCM pathogenesis as well. For the first time relocalization of the protein to the connective tissue was shown according to the Western-blot results. Conclusions. The data obtained allow us to understand a possible role of р70S6K1 in the regulation of stress-induced apoptotic signaling in cardiomyocytes.

  14. GREEN BANK TELESCOPE OBSERVATIONS OF THE NH3 (3, 3) AND (6, 6) TRANSITIONS TOWARD SAGITTARIUS A MOLECULAR CLOUDS

    International Nuclear Information System (INIS)

    Minh, Young Chol; Liu, Hauyu Baobab; Ho, Paul T. P.; Hsieh, Pei-Ying; Su, Yu-Nung; Kim, Sungsoo S.; Wright, Melvyn

    2013-01-01

    Ammonia (3, 3) and (6, 6) transitions have been observed using the Green Bank Telescope toward the Sgr A region. The gas is mainly concentrated in 50 km s –1 and 20 km s –1 clouds located in a plane inclined to the galactic plane. These 'main' clouds appear to be virialized and influenced by the expansion of the supernova remnant Sgr A East. The observed emission shows very complicated features in the morphology and velocity structure. Gaussian multi-component fittings of the observed spectra revealed that various 'streaming' gas components exist all over the observed region. These components include those previously known as 'streamers' and 'ridges', but most of these components appear not to be directly connected to the major gas condensations (the 50 km s –1 and 20 km s –1 clouds). They are apparently located out of the galactic plane, and they may have a different origin than the major gas condensations. Some of the streaming components are expected to be sources that feed the circumnuclear disk of our Galactic center directly and episodically. They may also evolve differently than major gas condensations under the influence of the activities of the Galactic center

  15. Ribosomal protein S6 phosphorylation is controlled by TOR and modulated by PKA in Candida albicans.

    Science.gov (United States)

    Chowdhury, Tahmeena; Köhler, Julia R

    2015-10-01

    TOR and PKA signaling pathways control eukaryotic cell growth and proliferation. TOR activity in model fungi, such as Saccharomyces cerevisiae, responds principally to nutrients, e.g., nitrogen and phosphate sources, which are incorporated into the growing cell mass; PKA signaling responds to the availability of the cells' major energy source, glucose. In the fungal commensal and pathogen, Candida albicans, little is known of how these pathways interact. Here, the signal from phosphorylated ribosomal protein S6 (P-S6) was defined as a surrogate marker for TOR-dependent anabolic activity in C. albicans. Nutritional, pharmacologic and genetic modulation of TOR activity elicited corresponding changes in P-S6 levels. The P-S6 signal corresponded to translational activity of a GFP reporter protein. Contributions of four PKA pathway components to anabolic activation were then examined. In high glucose concentrations, only Tpk2 was required to upregulate P-S6 to physiologic levels, whereas all four tested components were required to downregulate P-S6 in low glucose. TOR was epistatic to PKA components with respect to P-S6. In many host niches inhabited by C. albicans, glucose is scarce, with protein being available as a nitrogen source. We speculate that PKA may modulate TOR-dependent cell growth to a rate sustainable by available energy sources, when monomers of anabolic processes, such as amino acids, are abundant. © 2015 John Wiley & Sons Ltd.

  16. Principle Component Analysis of two-particle correlations in PbPb and pPb collisions at CMS

    CERN Document Server

    AUTHOR|(CDS)2076725

    2015-01-01

    A Principle Component Analysis (PCA) of two-particle azimuthal correlations as a function of transverse momentum ($p_T$) is presented in PbPb collisions at 2.76 TeV and high-multiplicity pPb collisions at 5.02 TeV. The data were recorded using the CMS detector at the LHC. It was shown that factorization breaking of two-particle azimuthal correlations can be attributed to the effect of initial-state fluctuations. Using a PCA approach, Fourier coefficients of observed two-particle azimuthal correlations as a function of both particles $p_T$ are characterized into leading and sub-leading mode terms. The leading modes are essentially equivalent to anisotropy harmonics ($v_n$) previously extracted from two-particle correlation methods as a function of $p_T$. The sub-leading modes represent the largest sources of factorization breaking. In the context of hydrodynamic models, they are a direct consequence of initial-state fluctuations. The results are presented over a wide range of centrality and event multiplicity....

  17. Virtual Bronchoscopy for Diagnosis of Recurrent Respiratory Papillomatosis

    Directory of Open Access Journals (Sweden)

    Chin-Hung Chang

    2006-01-01

    Full Text Available Virtual bronchoscopy is a new method for viewing helical/spiral computed tomography (CT images of the tracheobronchial trees. Using commercially available software to process the CT data, the tracheobronchial trees can be inspected through a series of three-dimensional images. Recently, this technique has been increasingly used to detect benign and malignant airway stenosis. We report the findings of virtual bronchoscopy in a 41-year-old man with recurrent respiratory papillomatosis (RRP. Several tiny nodules were evident in the lower trachea. Fiberoptic bronchoscopy was performed 1 month later during a planned surgery for laryngeal papillomas, and the findings were in agreement with virtual bronchoscopy. Detection of intrabronchial spreading in RRP is important since peripheral seeding of RRP can cause complications, including recurrent pneumonia, obstructive atelectasis, hemoptysis, and, rarely, may degenerate to squamous cell carcinoma. Virtual bronchoscopy is an alternative method for inspecting the tracheobronchial trees in patients with RRP when laryngeal papillomas impede fiberoptic bronchoscopy.

  18. Macronutrients and micronutrients of soybean oil bodies extracted at different pH.

    Science.gov (United States)

    Chen, Yeming; Cao, Yanyun; Zhao, Luping; Kong, Xiangzhen; Hua, Yufei

    2014-07-01

    In this study, the macronutrients and micronutrients of pH 6.8, 8.0, 9.5, and 11.0 extracted soybean oil bodies (OBs) were examined, revealing that soybean OBs might be used as a natural carrier for bioactive components (unsaturated fatty acids, phospholipid, tocopherol, and phytosterol). pH 6.8 extracted OBs (dry basis) contained 85.88% neutral lipid, 8.18% protein, and 5.85% polar lipid (mainly phospholipid) by gravimetric analysis. The percentage of neutral lipid was increased, while those of protein and polar lipid were decreased with increasing pH. Tocopherol (about 75 mg/100 g neutral lipid of OBs) was not affected, while phytosterol was decreased (136 to 110 mg/100 g neutral lipid of OBs) with increasing pH. The detectable total monosaccaride (galactosamine, glucosamine, and glucose) content of extracted OBs was low and also decreased (35.80 to 6.13 mg/100 g neutral lipid of OBs) with increasing pH. The protein of extracted OBs had higher percentage of essential amino acids than soybean protein isolate with tryptophan and methionine as limited amino acids. The fatty acid composition of extracted OBs was rich in linoleic acid (about 59%), oleic acid (about 20%), and α-linolenic acid (about 7%). Oil bodies (OBs) from soybean and other plant seeds are greatly examined owing to their potential utilizations in food ingredients. The determination of its macronutrients and micronutrients would be very meaningful for its efficient utilization in the future. © 2014 Institute of Food Technologists®

  19. Use of nonelectrolytes reveals the channel size and oligomeric constitution of the Borrelia burgdorferi P66 porin.

    Directory of Open Access Journals (Sweden)

    Iván Bárcena-Uribarri

    Full Text Available In the Lyme disease spirochete Borrelia burgdorferi, the outer membrane protein P66 is capable of pore formation with an atypical high single-channel conductance of 11 nS in 1 M KCl, which suggested that it could have a larger diameter than 'normal' Gram-negative bacterial porins. We studied the diameter of the P66 channel by analyzing its single-channel conductance in black lipid bilayers in the presence of different nonelectrolytes with known hydrodynamic radii. We calculated the filling of the channel with these nonelectrolytes and the results suggested that nonelectrolytes (NEs with hydrodynamic radii of 0.34 nm or smaller pass through the pore, whereas neutral molecules with greater radii only partially filled the channel or were not able to enter it at all. The diameter of the entrance of the P66 channel was determined to be ≤1.9 nm and the channel has a central constriction of about 0.8 nm. The size of the channel appeared to be symmetrical as judged from one-sidedness of addition of NEs. Furthermore, the P66-induced membrane conductance could be blocked by 80-90% by the addition of the nonelectrolytes PEG 400, PEG 600 and maltohexaose to the aqueous phase in the low millimolar range. The analysis of the power density spectra of ion current through P66 after blockage with these NEs revealed no chemical reaction responsible for channel block. Interestingly, the blockage of the single-channel conductance of P66 by these NEs occurred in about eight subconductance states, indicating that the P66 channel could be an oligomer of about eight individual channels. The organization of P66 as a possible octamer was confirmed by Blue Native PAGE and immunoblot analysis, which both demonstrated that P66 forms a complex with a mass of approximately 460 kDa. Two dimension SDS PAGE revealed that P66 is the only polypeptide in the complex.

  20. Cdt1p, through its interaction with Mcm6p, is required for the formation, nuclear accumulation and chromatin loading of the MCM complex.

    Science.gov (United States)

    Wu, Rentian; Wang, Jiafeng; Liang, Chun

    2012-01-01

    Regulation of DNA replication initiation is essential for the faithful inheritance of genetic information. Replication initiation is a multi-step process involving many factors including ORC, Cdt1p, Mcm2-7p and other proteins that bind to replication origins to form a pre-replicative complex (pre-RC). As a prerequisite for pre-RC assembly, Cdt1p and the Mcm2-7p heterohexameric complex accumulate in the nucleus in G1 phase in an interdependent manner in budding yeast. However, the nature of this interdependence is not clear, nor is it known whether Cdt1p is required for the assembly of the MCM complex. In this study, we provide the first evidence that Cdt1p, through its interaction with Mcm6p with the C-terminal regions of the two proteins, is crucial for the formation of the MCM complex in both the cytoplasm and nucleoplasm. We demonstrate that disruption of the interaction between Cdt1p and Mcm6p prevents the formation of the MCM complex, excludes Mcm2-7p from the nucleus, and inhibits pre-RC assembly and DNA replication. Our findings suggest a function for Cdt1p in promoting the assembly of the MCM complex and maintaining its integrity by interacting with Mcm6p.

  1. The supplementation of low-P diets with microbial 6-phytase expressed in Aspergillus oryzae improves P digestibility in sows.

    Science.gov (United States)

    Torrallardona, D; Llauradó, L; Broz, J

    2012-12-01

    Two trials were conducted to evaluate a novel microbial 6-phytase expressed in Aspergillus oryzae (Ronozyme HiPhos; DSM Nutritional Products, Basel, Switzerland) in gestating and lactating sows. In the first trial, 24 sows (Duroc × Landrace; 223 kg BW) were offered, at 16 d of gestation, a low-P control diet (formulated to provide 4.0 g total P/kg; 1.5 g digestible P/kg) supplemented with 0, 500, or 1000 phytase activity (FYT)/kg of phytase. Two weeks later, fresh feces were sampled from all sows and the apparent total tract digestibility of P was measured using TiO(2) as indigestible marker. Phytase supplementation did not (P > 0.10) affect the total tract digestibility of P but reduced (P phytase. After 2 wk, fresh feces were sampled from all sows and the apparent total tract digestibility of P was measured using TiO(2) as indigestible marker. Phytase supplementation improved (P phytase tested increased the apparent total tract digestibility of P in sows and reduced P excretion in feces.

  2. Molecular dynamics analysis reveals structural insights into mechanism of nicotine N-demethylation catalyzed by tobacco cytochrome P450 mono-oxygenase.

    Directory of Open Access Journals (Sweden)

    Shan Wang

    Full Text Available CYP82E4, a cytochrome P450 monooxygenase, has nicotine N-demethylase (NND activity, which mediates the bioconversion of nicotine into nornicotine in senescing tobacco leaves. Nornicotine is a precursor of the carcinogen, tobacco-specific nitrosamine. CYP82E3 is an ortholog of CYP82E4 with 95% sequence identity, but it lacks NND activity. A recent site-directed mutagenesis study revealed that a single amino acid substitution, i.e., cysteine to tryptophan at the 330 position in the middle of protein, restores the NND activity of CYP82E3 entirely. However, the same amino acid change caused the loss of the NND activity of CYP82E4. To determine the mechanism of the functional turnover of the two molecules, four 3D structures, i.e., the two molecules and their corresponding cys-trp mutants were modeled. The resulting structures exhibited that the mutation site is far from the active site, which suggests that no direct interaction occurs between the two sites. Simulation studies in different biological scenarios revealed that the mutation introduces a conformation drift with the largest change at the F-G loop. The dynamics trajectories analysis using principal component analysis and covariance analysis suggests that the single amino acid change causes the opening and closing of the transfer channels of the substrates, products, and water by altering the motion of the F-G and B-C loops. The motion of helix I is also correlated with the motion of both the F-G loop and the B-C loop and; the single amino acid mutation resulted in the curvature of helix I. These results suggest that the single amino acid mutation outside the active site region may have indirectly mediated the flexibility of the F-G and B-C loops through helix I, causing a functional turnover of the P450 monooxygenase.

  3. Functional analyses of GB virus B p13 protein: development of a recombinant GB virus B hepatitis virus with a p7 protein

    DEFF Research Database (Denmark)

    Takikawa, Shingo; Engle, Ronald E; Emerson, Suzanne U

    2006-01-01

    GB virus B (GBV-B), which infects tamarins, is the virus most closely related to hepatitis C virus (HCV). HCV has a protein (p7) that is believed to form an ion channel. It is critical for viability. In vitro studies suggest that GBV-B has an analogous but larger protein (p13). We found...... plus part of p7) was nonviable. However, a mutant lacking amino acid 614-669 (p6) produced high titer viremia and acute resolving hepatitis; viruses recovered from both animals lacked the deleted sequence and had no other mutations. Thus, p6 was dispensable but p7 was essential for infectivity...... processing at both sites, suggesting that p13 is processed into two components (p6 and p7). Mutants with substitution at amino acid 669 or 681 were viable in vivo, but the recovered viruses had changes at amino acid 669 and 681, respectively, which restored cleavage. A mutant lacking amino acid 614-681 (p6...

  4. Functional analyses of GB virus B p13 protein: Development of a recombinant GB virus B hepatitis virus with a p7 protein

    DEFF Research Database (Denmark)

    Takikawa, Shingo; Engle, Ronald E; Emerson, Suzanne U

    2006-01-01

    GB virus B (GBV-B), which infects tamarins, is the virus most closely related to hepatitis C virus (HCV). HCV has a protein (p7) that is believed to form an ion channel. It is critical for viability. In vitro studies suggest that GBV-B has an analogous but larger protein (p13). We found...... plus part of p7) was nonviable. However, a mutant lacking amino acid 614-669 (p6) produced high titer viremia and acute resolving hepatitis; viruses recovered from both animals lacked the deleted sequence and had no other mutations. Thus, p6 was dispensable but p7 was essential for infectivity...... processing at both sites, suggesting that p13 is processed into two components (p6 and p7). Mutants with substitution at amino acid 669 or 681 were viable in vivo, but the recovered viruses had changes at amino acid 669 and 681, respectively, which restored cleavage. A mutant lacking amino acid 614-681 (p6...

  5. Blocking S1P interaction with S1P{sub 1} receptor by a novel competitive S1P{sub 1}-selective antagonist inhibits angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Yasuyuki, E-mail: y.fujii@po.rd.taisho.co.jp [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Igarashi, Yasuyuki [Laboratory of Biomembrane and Biofunctional Chemistry, Hokkaido University, Sapporo, Hokkaido 060-0812 (Japan); Goitsuka, Ryo [Division of Development and Aging, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba 278-0022 (Japan)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer The effect of a newly developed S1P{sub 1}-selective antagonist on angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1} is a critical component of VEGF-related angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vitro activity to inhibit angiogenesis. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vivo activity to inhibit angiogenesis. Black-Right-Pointing-Pointer The efficacy of S1P{sub 1}-selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P{sub 1}) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P{sub 1} and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P{sub 1}-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P{sub 1} antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P{sub 1} is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

  6. RNA substrate length as an indicator of exosome interactions in vivo [version 2; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Clémentine Delan-Forino

    2017-07-01

    Full Text Available Background: The exosome complex plays key roles in RNA processing and degradation in Eukaryotes and Archaea. Outstanding structural studies identified multiple pathways for RNA substrates into the exosome in vitro, but identifying the pathway followed by individual RNA species in vivo remains challenging. Methods: We attempted to address this question using RNase protection. In vivo RNA-protein crosslinking (CRAC was applied to the exosome component Rrp44/Dis3, which has both endonuclease and exonuclease activity. During CRAC, the exosome was purified under native conditions and subjected to RNase digestion, prior to protein denaturation and cDNA cloning. The resulting high-throughput sequence reads were stratified by length of the cDNA sequence. This should reflect RNA fragment lengths, and therefore the RNA region that was protected by exosome binding. We anticipated major read lengths of ~30nt and ~10nt, reflecting the “central channel” and “direct access” routes to the Rrp44 exonuclease active site observed in vitro. Results: Unexpectedly, no clear peak was observed at 30nt, whereas a broad peak was seen around 20nt. The expected ~10nt peak was seen, and showed strong elevation in strains lacking exonuclease activity. Unexpectedly, this peak was suppressed by point mutations in the Rrp44 endonuclease active site. This indicates that the short fragments are degraded by the exonuclease activity of Rrp44, but also suggests that at least some may be generated by endonuclease activity. Conclusions: The absence of 30nt protected fragments may reflect obligatory binding of cofactors at the entrance to the exosome central channel in vivo. The presence of ~20nt fragments apparently indicates an access route not yet reported from in vitro studies. Confident mapping of 10nt reads is challenging, but they are clearly derived from a subset of exosome targets. In particular, pre-rRNA species, which are major exosome targets, are strongly

  7. Experimental Observation of Three-Component New Fermions in Topological Semimetal MoP

    Science.gov (United States)

    Lv, B. Q.; Feng, Z.-L.; Xu, Q.-N.; Ma, J.-Z.; Kong, L.-Y.; Richard, Pierre; Huang, Y.-B.; Strocov, V. N.; Fang, C.; Weng, H.-M.; Shi, Y.-G.; Qian, Tian; Ding, Hong; Paul Scherrer Institute, Swiss Light Source, CH-5232 Villigen PSI, Switzerland Team; Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics Team; University of Chinese Academy of Sciences, Beijing 100190, China Team; Collaborative Innovation Center of Quantum Matter, Beijing, China Collaboration; Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China Team

    Condensed matter systems can host quasiparticle excitations that are analogues to elementary particles such as Majorana, Weyl, and Dirac fermions. Recent advances in band theory have expanded the classification of fermions in crystals, and revealed crystal symmetry-protected electron excitations that have no high-energy counterparts. Here, using angle-resolved photoemission spectroscopy, we demonstrate the existence of a triply degenerate point in the electronic structure of MoP crystal, where the quasiparticle excitations are beyond the Majorana-Weyl-Dirac classification. Furthermore, we observe pairs of Weyl points in the bulk electronic structure coexisting with the new fermions, thus introducing a platform for studying the interplay between different types of fermions. We thank Binbin Fu, Nan Xu, and Xin Gao for the assistance in the ARPES experiments.

  8. Principal component analysis of biometric traits to reveal body confirmation in local hill cattle of Himalayan state of Himachal Pradesh, India.

    Science.gov (United States)

    Verma, Deepak; Sankhyan, Varun; Katoch, Sanjeet; Thakur, Yash Pal

    2015-12-01

    In the present study, biometric traits (body length [BL], heart girth [HG], paunch girth (PG), forelimb length (FLL), hind limb length (HLL), face length, forehead width, forehead length, height at hump, hump length (HL), hook to hook distance, pin to pin distance, tail length (TL), TL up to switch, horn length, horn circumference, and ear length were studied in 218 adult hill cattle of Himachal Pradesh for phenotypic characterization. Morphological and biometrical observations were recorded on 218 hill cattle randomly selected from different districts within the breeding tract. Multivariate statistics and principal component analysis are used to account for the maximum portion of variation present in the original set of variables with a minimum number of composite variables through Statistical software, SAS 9.2. Five components were extracted which accounted for 65.9% of variance. The first component explained general body confirmation and explained 34.7% variation. It was represented by significant loading for BL, HG, PG, FLL, and HLL. Communality estimate ranged from 0.41 (HL) to 0.88 (TL). Second, third, fourth, and fifth component had a high loading for tail characteristics, horn characteristics, facial biometrics, and rear body, respectively. The result of component analysis of biometric traits suggested that indigenous hill cattle of Himachal Pradesh are small and compact size cattle with a medium hump, horizontally placed short ears, and a long tail. The study also revealed that factors extracted from the present investigation could be used in breeding programs with sufficient reduction in the number of biometric traits to be recorded to explain the body confirmation.

  9. UDP/P2Y6 receptor signaling regulates IgE-dependent degranulation in human basophils

    Directory of Open Access Journals (Sweden)

    Manabu Nakano

    2017-10-01

    Conclusions: This study showed that UDP/P2Y6 receptor signaling is involved in the regulation of IgE-dependent degranulation in basophils, which might stimulate the P2Y6 receptor via the autocrine secretion of UTP. Thus, this receptor represents a potential target to regulate IgE-dependent degranulation in basophils during allergic diseases.

  10. Atomic structure of the sweet-tasting protein thaumatin I at pH 8.0 reveals the large disulfide-rich region in domain II to be sensitive to a pH change

    Energy Technology Data Exchange (ETDEWEB)

    Masuda, Tetsuya, E-mail: t2masuda@kais.kyoto-u.ac.jp [Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Department of Natural Resources, Graduate School of Global Environmental Studies, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Ohta, Keisuke [Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Department of Natural Resources, Graduate School of Global Environmental Studies, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Mikami, Bunzo [Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Kitabatake, Naofumi [Department of Foods and Human Nutrition, Notre Dame Seishin University, Okayama 700-8516 (Japan); Tani, Fumito [Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Department of Natural Resources, Graduate School of Global Environmental Studies, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan)

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer Structure of a recombinant thaumatin at pH 8.0 determined at a resolution of 1.0 A. Black-Right-Pointing-Pointer Substantial fluctuations of a loop in domain II was found in the structure at pH 8.0. Black-Right-Pointing-Pointer B-factors for Lys137, Lys163, and Lys187 were significantly affected by pH change. Black-Right-Pointing-Pointer An increase in mobility might play an important role in the heat-induced aggregation. -- Abstract: Thaumatin, an intensely sweet-tasting plant protein, elicits a sweet taste at 50 nM. Although the sweetness remains when thaumatin is heated at 80 Degree-Sign C for 4 h under acid conditions, it rapidly declines when heating at a pH above 6.5. To clarify the structural difference at high pH, the atomic structure of a recombinant thaumatin I at pH 8.0 was determined at a resolution of 1.0 A. Comparison to the crystal structure of thaumatin at pH 7.3 and 7.0 revealed the root-mean square deviation value of a C{alpha} atom to be substantially greater in the large disulfide-rich region of domain II, especially residues 154-164, suggesting that a loop region in domain II to be affected by solvent conditions. Furthermore, B-factors of Lys137, Lys163, and Lys187 were significantly affected by pH change, suggesting that a striking increase in the mobility of these lysine residues, which could facilitate a reaction with a free sulfhydryl residue produced via the {beta}-elimination of disulfide bonds by heating at a pH above 7.0. The increase in mobility of lysine residues as well as a loop region in domain II might play an important role in the heat-induced aggregation of thaumatin above pH 7.0.

  11. Formation Mechanism of Magnesium Ammonium Phosphate Stones: A Component Analysis of Urinary Nanocrystallites

    Directory of Open Access Journals (Sweden)

    Xin-Yuan Sun

    2015-01-01

    Full Text Available The components of urinary nanocrystallites in patients with magnesium ammonium phosphate (MAP stones were analyzed by X-ray diffraction (XRD, Fourier-transform infrared (FT-IR spectrometer, high-resolution transmission electron microscopy (HRTEM, selected area electron diffraction (SAED, fast Fourier transformation (FFT, and energy-dispersive X-ray spectroscopy (EDS. The main components of the stones were MAP hexahydrate (MAP·6H2O, magnesium hydrogen phosphate trihydrate (MgHPO4·3H2O, and a small amount of calcium phosphate (CaP, while the main components of urinary nanocrystallites were MgHPO4·3H2O, CaP, and MAP monohydrate (MAP·H2O. MAP·H2O induced the formation of MAP stones as seed crystals. MgHPO4·3H2O was accompanied by the appearance of MAP·6H2O. The formation mechanism of MAP stones and influencing factors were discussed on the basis of the components of urine nanocrystallites. A model diagram of MAP stone formation was also put forward based on the results. Formation of MAP stones was closely related to the presence of high amounts of MAP crystallites in urine. Urinary crystallite condition and changes in urine components could indicate the activity of stone diseases.

  12. THE EXON 5, 6, 7, 8 OF P53 MUTATIONS IN ORAL SQUAMOUS CELLS CARCINOMA

    Directory of Open Access Journals (Sweden)

    Retno P Rahayu

    2012-04-01

    Full Text Available Genetic instability may underlie the etiology of multistep carcinogenesis. The altered p53 gene observed in tumors may represent the expression of such instability and may allow the accumulation of other gene alterations caused by multiple mechanism. p53 gene is the guardian of the genome, that is why we pay more attention to this gene. In this study, we evaluated the significance of p53 mutation in 55 patient with oral squamous carcinoma. Thirty among them underwent well-differentiated carcinoma, while the remaining 25 patients underwent poorly differentiated carcinoma. The mutations were detected by PCR-SSCP (Single strand Conformational Polymorphism analysis in the region between exon 5 and exon 8. The results indicated that the p53 mutation in exon 5 (40%, exon 6 (28%, exon 7 (24% and exon 8 (8% were associated with poorly differentiated carcinoma, whereas mutation in exon 5 (10%, exon 6 (30%, exon 7 (40% and exon 8 (20% were associated with well-differentiated carcinoma. These observations suggest that p53 mutation in exon 5, 6, and 7 have strong correlation with poorly differentiated in oral squamous carcinoma while well-differentiated level was related with mutation in exon 6,7 and 8.

  13. Dek-can rearrangement in translocation (6;9)(p23;q34)

    NARCIS (Netherlands)

    Soekarman, D.; von Lindern, M.; van der Plas, D. C.; Selleri, L.; Bartram, C. R.; Martiat, P.; Culligan, D.; Padua, R. A.; Hasper-Voogt, K. P.; Hagemeijer, A.

    1992-01-01

    The translocation (6;9)(p23;q34) is mainly found in specific subtypes of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The diagnosis of this translocation is not easy since the cytogenetic change is quite subtle. The two genes involved in this translocation were recently isolated

  14. PF-4708671, a specific inhibitor of p70 ribosomal S6 kinase 1, activates Nrf2 by promoting p62-dependent autophagic degradation of Keap1

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Su [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2015-10-23

    p70 ribosomal S6 kinase 1 (S6K1) is an important serine/threonine kinase and downstream target of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. PF-4708671 is a specific inhibitor of S6K1, and prevents S6K1-mediated phosphorylation of the S6 protein. PF-4708671 treatment often leads to apoptotic cell death. However, the protective mechanism against PF-4708671-induced cell death has not been elucidated. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is essential for protecting cells against oxidative stress. p62, an adaptor protein in the autophagic process, enhances Nrf2 activation through the impairment of Keap1 activity. In this study, we showed that PF-4708671 induces autophagic Keap1 degradation-mediated Nrf2 activation in p62-dependent manner. Furthermore, p62-dependent Nrf2 activation plays a crucial role in protecting cells from PF-4708671-mediated apoptosis. - Highlights: • PF-4708671, a S6K1-specific inhibitor, prevents S6K1-mediated S6 phosphorylation. • However, PF-4708671 treatment often leads to apoptotic cell death. • Protective mechanism against PF-4708671-induced cell death remains to be elucidated. • PF-4708671 induced p62-dependent, autophagic Keap1 degradation-mediated Nrf2 activation. • p62-dependent Nrf2 activation protects cells from PF-4708671-mediated apoptosis.

  15. IL-6 modulates hepatocyte proliferation via induction of HGF/p21cip1: Regulation by SOCS3

    International Nuclear Information System (INIS)

    Sun Rui; Jaruga, Barbara; Kulkarni, Shailin; Sun Haoyu; Gao Bin

    2005-01-01

    The precise role of IL-6 in liver regeneration and hepatocyte proliferation is controversial and the role of SOCS3 in liver regeneration remains unknown. Here we show that in vitro treatment with IL-6 inhibited primary mouse hepatocyte proliferation. IL-6 induced p21 cip1 protein expression in primary mouse hepatocytes. Disruption of the p21 cip1 gene abolished the inhibitory effect of IL-6 on cell proliferation. Co-culture with nonparenchymal liver cells diminished IL-6 inhibition of hepatocyte proliferation, which was likely due to IL-6 stimulation of nonparenchymal cells to produce HGF. Finally, IL-6 induced higher levels of p21 cip1 protein expression and a slightly stronger inhibition of cell proliferation in SOCS3 +/- mouse hepatocytes compared to wild-type hepatocytes, while liver regeneration was enhanced and prolonged in SOCS3 +/- mice. Our findings suggest that IL-6 directly inhibits hepatocyte proliferation via a p21 cip1 -dependent mechanism and indirectly enhances hepatocyte proliferation via stimulating nonparenchymal cells to produce HGF. SOCS3 negatively regulates liver regeneration

  16. Electron-impact excitation cross sections of the higher argon 3p5np (n=5,6,7) levels

    International Nuclear Information System (INIS)

    Weber, Tobin; Boffard, John B.; Lin, Chun C.

    2003-01-01

    We have measured the electron-impact excitation cross sections for argon into the ten levels of 3p 5 5p configuration, as well as numerous levels of the 3p 5 6p and 3p 5 7p configurations. Fluorescence from the decay of the excited atoms to the levels of 3p 5 4s configuration was used to determine the optical-emission cross sections. These results were combined with transition probabilities to find apparent cross sections into the 3p 5 5p and 3p 5 6p levels. These new cross sections of the Ar(3p 5 np) levels along with the available Ne(2p 5 3p), Kr(4p 5 5p), and Xe(5p 5 6p) data help provide a global view of the excitation behaviors of the np 5 n ' p levels of the rare-gas series

  17. Serum fetuin-A levels are associated with serum triglycerides before and 6 months after bariatric surgery.

    Science.gov (United States)

    Verras, Christos G; Christou, Georgios A; Simos, Yannis V; Ayiomamitis, George D; Melidonis, Andreas J; Kiortsis, Dimitrios N

    2017-07-01

    The elucidation of the changes of fetuin-A in the context of bariatric surgery. Twenty obese patients (8 males, 12 females; body mass index = 42.5±3.4 kg/m2) were studied at baseline and 6 months after bariatric surgery. Serum fetuin-A levels did not differ with regard to the presence of each individual component of the Metabolic Syndrome (MetS) at baseline, except for hypertriglyceridaemia [increased serum fetuin-A levels (p=0.011)]. Circulating fetuin-A was positively correlated with serum triglycerides (TG) (r=0.461, p=0.047) and negatively correlated with serum globulins (r=-0.477, p=0.033) and C-reactive protein (CRP) (r=-0.604, p=0.010), while it independently predicted TG at baseline. Circulating fetuin-A did not change during the 6 months either in the whole population or in the subgroups of patients who were positive for each individual component of MetS at baseline and negative for this component at 6 months of follow-up, except for hypertriglyceridaemia [reduction of serum fetuin-A levels (p=0.046)]. The subgroup of patients with a decrease in circulating fetuin-A during the 6 months was characterized by a smaller reduction of serum globulins (p=0.003) and CRP (p=0.049). The change in serum fetuin-A levels over the 6 months was positively correlated with the change in TG (r=0.592, p=0.006) and negatively correlated with the change in serum globulins (r=-0.523, p=0.018) and CRP (r=-.494, p=0.037). Circulating fetuin-A predicted serum triglycerides before as well as 6 months after bariatric surgery.

  18. Degradation of p53 by human Alphapapillomavirus E6 proteins shows a stronger correlation with phylogeny than oncogenicity.

    Directory of Open Access Journals (Sweden)

    Leiping Fu

    2010-09-01

    Full Text Available Human Papillomavirus (HPV E6 induced p53 degradation is thought to be an essential activity by which high-risk human Alphapapillomaviruses (alpha-HPVs contribute to cervical cancer development. However, most of our understanding is derived from the comparison of HPV16 and HPV11. These two viruses are relatively distinct viruses, making the extrapolation of these results difficult. In the present study, we expand the tested strains (types to include members of all known HPV species groups within the Alphapapillomavirus genus.We report the biochemical activity of E6 proteins from 27 HPV types representing all alpha-HPV species groups to degrade p53 in human cells. Expression of E6 from all HPV types epidemiologically classified as group 1 carcinogens significantly reduced p53 levels. However, several types not associated with cancer (e.g., HPV53, HPV70 and HPV71 were equally active in degrading p53. HPV types within species groups alpha 5, 6, 7, 9 and 11 share a most recent common ancestor (MRCA and all contain E6 ORFs that degrade p53. A unique exception, HPV71 E6 ORF that degraded p53 was outside this clade and is one of the most prevalent HPV types infecting the cervix in a population-based study of 10,000 women. Alignment of E6 ORFs identified an amino acid site that was highly correlated with the biochemical ability to degrade p53. Alteration of this amino acid in HPV71 E6 abrogated its ability to degrade p53, while alteration of this site in HPV71-related HPV90 and HPV106 E6s enhanced their capacity to degrade p53.These data suggest that the alpha-HPV E6 proteins' ability to degrade p53 is an evolved phenotype inherited from a most recent common ancestor of the high-risk species that does not always segregate with carcinogenicity. In addition, we identified an amino-acid residue strongly correlated with viral p53 degrading potential.

  19. Comparison of efficacy and satisfaction profile, between penile prosthesis implantation and oral PDE5 inhibitor tadalafil therapy, in men with nerve-sparing radical prostatectomy erectile dysfunction.

    Science.gov (United States)

    Megas, Georgios; Papadopoulos, Georgios; Stathouros, Georgios; Moschonas, Dimitrios; Gkialas, Ioannis; Ntoumas, Konstantinos

    2013-07-01

    WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Erectile dysfunction after nerve-sparing radical retropubic prostatectomy constitutes a challenge to the urologist. The mainstay of medical treatment after radical prostatectomy to restore spontaneous erectile function remains phosphodiesterase (PDE5) inhibitors, despite the fact that data from animal studies suggesting that PDE5 inhibitors can prevent smooth muscle apoptosis and fibrosis have not yet been extrapolated to humans because of a lack of standardized protocols. If the above treatment fails, second-line therapies such as intraurethral prostaglandins, penile injection therapy and vacuum devices are offered. When less invasive therapies are ineffective, interventions that preserve sexual function such as penile prosthesis implantation become the treatment of choice. Our study reveals the alternative of penile prosthesis implantation as first-line treatment in erectile dysfunction after nerve-sparing radical prostatectomy. It also highlights its superiority to the oral PDE5 inhibitor treatment, regarding the erection, frequency, firmness, maintenance and penetration ability. This suggests that a concept of an early penile intervention in the future would be promising for those patients who wish to remain sexually active without depending on oral formulations with doubtful and delayed results. To evaluate the outcome of penile prosthesis surgery in comparison to oral phosphodiesterase type 5 (PDE5) inhibitor administration, in men with erectile dysfunction after nerve-sparing radical prostatectomy, as early penile intervention therapy. A total of 174 patients treated by nerve-sparing retropubic radical prostatectomy (RRP) for clinically localized prostate cancer, between January 2006 and September 2009 enrolled in the study, 153 patients fulfilled the inclusion criteria, and 69 (45%) patients presented with post-RRP erectile dysfunction 6 months after primary surgery. Fifty-four patients were disease

  20. A search for the Δ- wave-function component in light nuclei

    International Nuclear Information System (INIS)

    Morris, C.L.; Zumbro, J.D.; Boudrie, R.L.

    1996-01-01

    We have studied the (π + , π ± p) reactions on 3 He, 4 He, 6 Li, and 7 Li at incident energy 500 MeV in quasi-free kinematics. A signature attributable to pre-existing Δ components of the ground state wave function is observed