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Sample records for ecf sigma factor

  1. Characterization of Five ECF Sigma Factors in the Genome of Pseudomonas syringae pv. syringae B728a

    PubMed Central

    Thakur, Poulami Basu; Vaughn-Diaz, Vanessa L.; Greenwald, Jessica W.; Gross, Dennis C.

    2013-01-01

    Pseudomonas syringae pv. syringae B728a, a bacterial pathogen of bean, utilizes large surface populations and extracellular signaling to initiate a fundamental change from an epiphytic to a pathogenic lifestyle. Extracytoplasmic function (ECF) sigma (σ) factors serve as important regulatory factors in responding to various environmental signals. Bioinformatic analysis of the B728a genome revealed 10 ECF sigma factors. This study analyzed deletion mutants of five previously uncharacterized ECF sigma factor genes in B728a, including three FecI-type ECF sigma factors (ECF5, ECF6, and ECF7) and two ECF sigma factors placed in groups ECF11 and ECF18. Transcriptional profiling by qRT-PCR analysis of ECF sigma factor mutants was used to measure expression of their associated anti-sigma and outer membrane receptor proteins, and expression of genes associated with production of extracellular polysaccharides, fimbriae, glycine betaine and syringomycin. Notably, the B728aΔecf7 mutant displayed reduced swarming and had decreased expression of CupC fimbrial genes. Growth and pathogenicity assays, using a susceptible bean host, revealed that none of the tested sigma factor genes are required for in planta growth and lesion formation. PMID:23516563

  2. Knockout of Extracytoplasmic Function Sigma Factor ECF-10 Affects Stress Resistance and Biofilm Formation in Pseudomonas putida KT2440

    PubMed Central

    Tettmann, Beatrix; Dötsch, Andreas; Armant, Olivier; Fjell, Christopher D.

    2014-01-01

    Pseudomonas putida is a Gram-negative soil bacterium which is well-known for its versatile lifestyle, controlled by a large repertoire of transcriptional regulators. Besides one- and two-component regulatory systems, the genome of P. putida reveals 19 extracytoplasmic function (ECF) sigma factors involved in the adaptation to changing environmental conditions. In this study, we demonstrate that knockout of extracytoplasmic function sigma factor ECF-10, encoded by open reading frame PP4553, resulted in 2- to 4-fold increased antibiotic resistance to quinolone, β-lactam, sulfonamide, and chloramphenicol antibiotics. In addition, the ECF-10 mutant exhibited enhanced formation of biofilms after 24 h of incubation. Transcriptome analysis using Illumina sequencing technology resulted in the detection of 12 genes differentially expressed (>2-fold) in the ECF-10 knockout mutant strain compared to their levels of expression in wild-type cells. Among the upregulated genes were ttgA, ttgB, and ttgC, which code for the major multidrug efflux pump TtgABC in P. putida KT2440. Investigation of an ECF-10 and ttgA double-knockout strain and a ttgABC-overexpressing strain demonstrated the involvement of efflux pump TtgABC in the stress resistance and biofilm formation phenotypes of the ECF-10 mutant strain, indicating a new role for this efflux pump beyond simple antibiotic resistance in P. putida KT2440. PMID:24907323

  3. Functional analysis of PSPTO_1203 a FecI-like ECF Sigma Factor of Pseudomonas syringae pv. tomato DC3000

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have been investigating how P. syringae responds to limited iron availability, a common stress in aerobic environments. We are mainly focused on the role of the extracytoplasmic function (ECF) sigma factors, which are one of the mechanisms used by bacteria to adjust gene regulation in response to...

  4. A two-component system regulates gene expression of the type IX secretion component proteins via an ECF sigma factor

    PubMed Central

    Kadowaki, Tomoko; Yukitake, Hideharu; Naito, Mariko; Sato, Keiko; Kikuchi, Yuichiro; Kondo, Yoshio; Shoji, Mikio; Nakayama, Koji

    2016-01-01

    The periodontopathogen Porphyromonas gingivalis secretes potent pathogenic proteases, gingipains, via the type IX secretion system (T9SS). This system comprises at least 11 components; however, the regulatory mechanism of their expression has not yet been elucidated. Here, we found that the PorY (PGN_2001)-PorX (PGN_1019)-SigP (PGN_0274) cascade is involved in the regulation of T9SS. Surface plasmon resonance (SPR) analysis revealed a direct interaction between a recombinant PorY (rPorY) and a recombinant PorX (rPorX). rPorY autophosphorylated and transferred a phosphoryl group to rPorX in the presence of Mn2+. These results demonstrate that PorX and PorY act as a response regulator and a histidine kinase, respectively, of a two component system (TCS), although they are separately encoded on the chromosome. T9SS component-encoding genes were down-regulated in a mutant deficient in a putative extracytoplasmic function (ECF) sigma factor, PGN_0274 (SigP), similar to the porX mutant. Electrophoretic gel shift assays showed that rSigP bound to the putative promoter regions of T9SS component-encoding genes. The SigP protein was lacking in the porX mutant. Co-immunoprecipitation and SPR analysis revealed the direct interaction between SigP and PorX. Together, these results indicate that the PorXY TCS regulates T9SS-mediated protein secretion via the SigP ECF sigma factor. PMID:26996145

  5. A two-component system regulates gene expression of the type IX secretion component proteins via an ECF sigma factor.

    PubMed

    Kadowaki, Tomoko; Yukitake, Hideharu; Naito, Mariko; Sato, Keiko; Kikuchi, Yuichiro; Kondo, Yoshio; Shoji, Mikio; Nakayama, Koji

    2016-01-01

    The periodontopathogen Porphyromonas gingivalis secretes potent pathogenic proteases, gingipains, via the type IX secretion system (T9SS). This system comprises at least 11 components; however, the regulatory mechanism of their expression has not yet been elucidated. Here, we found that the PorY (PGN_2001)-PorX (PGN_1019)-SigP (PGN_0274) cascade is involved in the regulation of T9SS. Surface plasmon resonance (SPR) analysis revealed a direct interaction between a recombinant PorY (rPorY) and a recombinant PorX (rPorX). rPorY autophosphorylated and transferred a phosphoryl group to rPorX in the presence of Mn(2+). These results demonstrate that PorX and PorY act as a response regulator and a histidine kinase, respectively, of a two component system (TCS), although they are separately encoded on the chromosome. T9SS component-encoding genes were down-regulated in a mutant deficient in a putative extracytoplasmic function (ECF) sigma factor, PGN_0274 (SigP), similar to the porX mutant. Electrophoretic gel shift assays showed that rSigP bound to the putative promoter regions of T9SS component-encoding genes. The SigP protein was lacking in the porX mutant. Co-immunoprecipitation and SPR analysis revealed the direct interaction between SigP and PorX. Together, these results indicate that the PorXY TCS regulates T9SS-mediated protein secretion via the SigP ECF sigma factor. PMID:26996145

  6. Extracytoplasmic Function (ECF) Sigma Factor Gene Regulation in Pseudomonas syringae: Integrated Molecular and Computational Characterization of PvdS-Regulated Promoters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The extracytoplasmic function (ECF) sigma factor PvdS regulates the expression of genes required for the biosynthesis and transport of pyoverdine, a siderophore that functions in iron acquisition. The production of pyoverdine is a distinctive trait of the fluorescent pseudomonads and the regulation ...

  7. Extracytoplasmic function (ECF) sigma factor σF is involved in Caulobacter crescentus response to heavy metal stress

    PubMed Central

    2012-01-01

    Background The α-proteobacterium Caulobacter crescentus inhabits low-nutrient environments and can tolerate certain levels of heavy metals in these sites. It has been reported that C. crescentus responds to exposure to various heavy metals by altering the expression of a large number of genes. Results In this work, we show that the ECF sigma factor σF is one of the regulatory proteins involved in the control of the transcriptional response to chromium and cadmium. Microarray experiments indicate that σF controls eight genes during chromium stress, most of which were previously described as induced by heavy metals. Surprisingly, σF itself is not strongly auto-regulated under metal stress conditions. Interestingly, σF-dependent genes are not induced in the presence of agents that generate reactive oxygen species. Promoter analyses revealed that a conserved σF-dependent sequence is located upstream of all genes of the σF regulon. In addition, we show that the second gene in the sigF operon acts as a negative regulator of σF function, and the encoded protein has been named NrsF (Negative regulator of sigma F). Substitution of two conserved cysteine residues (C131 and C181) in NrsF affects its ability to maintain the expression of σF-dependent genes at basal levels. Furthermore, we show that σF is released into the cytoplasm during chromium stress and in cells carrying point mutations in both conserved cysteines of the protein NrsF. Conclusion A possible mechanism for induction of the σF-dependent genes by chromium and cadmium is the inactivation of the putative anti-sigma factor NrsF, leading to the release of σF to bind RNA polymerase core and drive transcription of its regulon. PMID:22985357

  8. Transcriptional regulation of the operon encoding stress-responsive ECF sigma factor SigH and its anti-sigma factor RshA, and control of its regulatory network in Corynebacterium glutamicum

    PubMed Central

    2012-01-01

    Background The expression of genes in Corynebacterium glutamicum, a Gram-positive non-pathogenic bacterium used mainly for the industrial production of amino acids, is regulated by seven different sigma factors of RNA polymerase, including the stress-responsive ECF-sigma factor SigH. The sigH gene is located in a gene cluster together with the rshA gene, putatively encoding an anti-sigma factor. The aim of this study was to analyze the transcriptional regulation of the sigH and rshA gene cluster and the effects of RshA on the SigH regulon, in order to refine the model describing the role of SigH and RshA during stress response. Results Transcription analyses revealed that the sigH gene and rshA gene are cotranscribed from four sigH housekeeping promoters in C. glutamicum. In addition, a SigH-controlled rshA promoter was found to only drive the transcription of the rshA gene. To test the role of the putative anti-sigma factor gene rshA under normal growth conditions, a C. glutamicum rshA deletion strain was constructed and used for genome-wide transcription profiling with DNA microarrays. In total, 83 genes organized in 61 putative transcriptional units, including those previously detected using sigH mutant strains, exhibited increased transcript levels in the rshA deletion mutant compared to its parental strain. The genes encoding proteins related to disulphide stress response, heat stress proteins, components of the SOS-response to DNA damage and proteasome components were the most markedly upregulated gene groups. Altogether six SigH-dependent promoters upstream of the identified genes were determined by primer extension and a refined consensus promoter consisting of 45 original promoter sequences was constructed. Conclusions The rshA gene codes for an anti-sigma factor controlling the function of the stress-responsive sigma factor SigH in C. glutamicum. Transcription of rshA from a SigH-dependent promoter may serve to quickly shutdown the SigH-dependent stress

  9. σECF factors of gram-positive bacteria

    PubMed Central

    Souza, Bianca Mendes; Castro, Thiago Luiz de Paula; Carvalho, Rodrigo Dias de Oliveira; Seyffert, Nubia; Silva, Artur; Miyoshi, Anderson; Azevedo, Vasco

    2014-01-01

    The survival of bacteria to different environmental conditions depends on the activation of adaptive mechanisms, which are intricately driven through gene regulation. Because transcriptional initiation is considered to be the major step in the control of bacterial genes, we discuss the characteristics and roles of the sigma factors, addressing (1) their structural, functional and phylogenetic classification; (2) how their activity is regulated; and (3) the promoters recognized by these factors. Finally, we focus on a specific group of alternative sigma factors, the so-called σECF factors, in Bacillus subtilis and some of the main species that comprise the CMNR group, providing information on the roles they play in the microorganisms’ physiology and indicating some of the genes whose transcription they regulate. PMID:24921931

  10. Regulation of energy metabolism by the extracytoplasmic function (ECF) s factors of Arcobacter butzleri

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The extracytoplasmic function (ECF) s factors are fundamental for bacterial adaptation to distinct environments and for survival under different stress conditions. The emerging pathogen Arcobacter butzleri possesses seven putative pairs of s/anti-s factors belonging to the ECF family. Here, we repor...

  11. Rhodopseudomonas palustris CGA010 Proteome Implicates Extracytoplasmic Function Sigma Factor in Stress Response

    SciTech Connect

    Allen, Michael S.; Hurst, Gregory B.; Lu, Tse-Yuan S.; Perry, Leslie M.; Pan, Chongle; Lankford, Patricia K.; Pelletier, Dale A.

    2015-04-08

    Rhodopseudomonas palustris encodes 16 extracytoplasmic function (ECF) σ factors. In this paper, to begin to investigate the regulatory network of one of these ECF σ factors, the whole proteome of R. palustris CGA010 was quantitatively analyzed by tandem mass spectrometry from cultures episomally expressing the ECF σRPA4225 (ecfT) versus a WT control. Among the proteins with the greatest increase in abundance were catalase KatE, trehalose synthase, a DPS-like protein, and several regulatory proteins. Alignment of the cognate promoter regions driving expression of several upregulated proteins suggested a conserved binding motif in the -35 and -10 regions with the consensus sequence GGAAC-18N-TT. Additionally, the putative anti-σ factor RPA4224, whose gene is contained in the same predicted operon as RPA4225, was identified as interacting directly with the predicted response regulator RPA4223 by mass spectrometry of affinity-isolated protein complexes. Furthermore, another gene (RPA4226) coding for a protein that contains a cytoplasmic histidine kinase domain is located immediately upstream of RPA4225. The genomic organization of orthologs for these four genes is conserved in several other strains of R. palustris as well as in closely related α-Proteobacteria. Finally, taken together, these data suggest that ECF σRPA4225 and the three additional genes make up a sigma factor mimicry system in R. palustris.

  12. Rhodopseudomonas palustris CGA010 Proteome Implicates Extracytoplasmic Function Sigma Factor in Stress Response

    DOE PAGESBeta

    Allen, Michael S.; Hurst, Gregory B.; Lu, Tse-Yuan S.; Perry, Leslie M.; Pan, Chongle; Lankford, Patricia K.; Pelletier, Dale A.

    2015-04-08

    Rhodopseudomonas palustris encodes 16 extracytoplasmic function (ECF) σ factors. In this paper, to begin to investigate the regulatory network of one of these ECF σ factors, the whole proteome of R. palustris CGA010 was quantitatively analyzed by tandem mass spectrometry from cultures episomally expressing the ECF σRPA4225 (ecfT) versus a WT control. Among the proteins with the greatest increase in abundance were catalase KatE, trehalose synthase, a DPS-like protein, and several regulatory proteins. Alignment of the cognate promoter regions driving expression of several upregulated proteins suggested a conserved binding motif in the -35 and -10 regions with the consensus sequencemore » GGAAC-18N-TT. Additionally, the putative anti-σ factor RPA4224, whose gene is contained in the same predicted operon as RPA4225, was identified as interacting directly with the predicted response regulator RPA4223 by mass spectrometry of affinity-isolated protein complexes. Furthermore, another gene (RPA4226) coding for a protein that contains a cytoplasmic histidine kinase domain is located immediately upstream of RPA4225. The genomic organization of orthologs for these four genes is conserved in several other strains of R. palustris as well as in closely related α-Proteobacteria. Finally, taken together, these data suggest that ECF σRPA4225 and the three additional genes make up a sigma factor mimicry system in R. palustris.« less

  13. The sigma factors of Bacillus subtilis.

    PubMed Central

    Haldenwang, W G

    1995-01-01

    The specificity of DNA-dependent RNA polymerase for target promotes is largely due to the replaceable sigma subunit that it carries. Multiple sigma proteins, each conferring a unique promoter preference on RNA polymerase, are likely to be present in all bacteria; however, their abundance and diversity have been best characterized in Bacillus subtilis, the bacterium in which multiple sigma factors were first discovered. The 10 sigma factors thus far identified in B. subtilis directly contribute to the bacterium's ability to control gene expression. These proteins are not merely necessary for the expression of those operons whose promoters they recognize; in many instances, their appearance within the cell is sufficient to activate these operons. This review describes the discovery of each of the known B. subtilis sigma factors, their characteristics, the regulons they direct, and the complex restrictions placed on their synthesis and activities. These controls include the anticipated transcriptional regulation that modulates the expression of the sigma factor structural genes but, in the case of several of the B. subtilis sigma factors, go beyond this, adding novel posttranslational restraints on sigma factor activity. Two of the sigma factors (sigma E and sigma K) are, for example, synthesized as inactive precursor proteins. Their activities are kept in check by "pro-protein" sequences which are cleaved from the precursor molecules in response to intercellular cues. Other sigma factors (sigma B, sigma F, and sigma G) are inhibited by "anti-sigma factor" proteins that sequester them into complexes which block their ability to form RNA polymerase holoenzymes. The anti-sigma factors are, in turn, opposed by additional proteins which participate in the sigma factors' release. The devices used to control sigma factor activity in B, subtilis may prove to be as widespread as multiple sigma factors themselves, providing ways of coupling sigma factor activation to

  14. Studies of the extracytoplasmic function sigma factor PG0162 in Porphyromonas gingivalis.

    PubMed

    Dou, Y; Aruni, W; Muthiah, A; Roy, F; Wang, C; Fletcher, H M

    2016-06-01

    PG0162, annotated as an extracytoplasmic function (ECF) sigma factor in Porphyromonas gingivalis, is composed of 193 amino acids. As previously reported, the PG0162-deficient mutant, P. gingivalis FLL350 showed significant reduction in gingipain activity compared with the parental strain. Because this ECF sigma factor could be involved in the virulence regulation in P. gingivalis, its genetic properties were further characterized. A 5'-RACE analysis showed that the start of transcription of the PG0162 gene occurred from a guanine (G) residue 69 nucleotides upstream of the ATG translation initiation codon. The function of PG0162 as a sigma factor was confirmed in a run-off in vitro transcription assay using the purified rPG0162 and RNAP core enzyme from Escherichia coli with the PG0162 promoter as template. As an appropriate PG0162 inducing environmental signal is unknown, a strain overexpressing the PG0162 gene designated P. gingivalis FLL391 was created. Compared with the wild-type strain, transcriptome analysis of P. gingivalis FLL391 showed that approximately 24% of the genome displayed altered gene expression (260 upregulated genes; 286 downregulated genes). Two other ECF sigma factors (PG0985 and PG1660) were upregulated more than two-fold. The autoregulation of PG0162 was confirmed with the binding of the rPG0162 protein to the PG0162 promoter in electrophoretic mobility shift assay. In addition, the rPG0162 protein also showed the ability to bind to the promoter region of two genes (PG0521 and PG1167) that were most upregulated in P. gingivalis FLL391. Taken together, our data suggest that PG0162 is a sigma factor that may play an important role in the virulence regulatory network in P. gingivalis. PMID:26216199

  15. RNA-seq Analysis Reveals That an ECF σ Factor, AcsS, Regulates Achromobactin Biosynthesis in Pseudomonas syringae pv. syringae B728a

    PubMed Central

    Greenwald, Jessica W.; Greenwald, Charles J.; Philmus, Benjamin J.; Begley, Tadhg P.; Gross, Dennis C.

    2012-01-01

    Iron is an essential micronutrient for Pseudomonas syringae pv. syringae strain B728a and many other microorganisms; therefore, B728a has evolved methods of iron acquirement including the use of iron-chelating siderophores. In this study an extracytoplasmic function (ECF) sigma factor, AcsS, encoded within the achromobactin gene cluster is shown to be a major regulator of genes involved in the biosynthesis and secretion of this siderophore. However, production of achromobactin was not completely abrogated in the deletion mutant, implying that other regulators may be involved such as PvdS, the sigma factor that regulates pyoverdine biosynthesis. RNA-seq analysis identified 287 genes that are differentially expressed between the AcsS deletion mutant and the wild type strain. These genes are involved in iron response, secretion, extracellular polysaccharide production, and cell motility. Thus, the transcriptome analysis supports a role for AcsS in the regulation of achromobactin production and the potential activity of both AcsS and achromobactin in the plant-associated lifestyle of strain B728a. PMID:22529937

  16. Regulation of Motility Behavior in Myxococcus xanthus May Require an Extracytoplasmic-Function Sigma Factor

    PubMed Central

    Ward, Mandy J.; Lew, Helen; Treuner-Lange, Anke; Zusman, David R.

    1998-01-01

    Using interaction trap technology, we identified a putative extracytoplasmic-function (ECF) sigma factor (RpoE1) in Myxococcus xanthus, a bacterium which has a complex life cycle that includes fruiting body formation. The first domain of the response regulator protein FrzZ, a component of the Frz signal transduction system, was used as bait. Although the RpoE1 protein displayed no interactions with control proteins presented as bait, a weak interaction with a second M. xanthus response regulator (AsgA) was observed. While the specificity of the FrzZ-RpoE1 interaction therefore remains speculative, cloning and sequencing of the region surrounding rpoE1 localized it to a position downstream of the frzZ gene. A potential promoter site for binding of an ECF sigma factor was identified upstream of rpoE1, suggesting the gene may be autoregulated. However, primer extension studies suggested that transcription of rpoE1 occurs under both vegetative and developmental conditions from a ς70-like promoter. Dot blot analysis of RNA preparations confirmed the low-level, constitutive expression of rpoE1 during both stages of the life cycle. Analysis of an insertion mutant also indicated a role for RpoE1 under both vegetative and developmental conditions, since swarming was reduced on nutrient-rich agar and developmental aggregation was effected under starvation conditions, especially at high cell densities. An insertion mutation introduced into the gene directly downstream of rpoE1 (orf5) did not result in either swarming or developmental aggregation defects, even though the gene is transcribed as part of the same operon. Therefore, we propose that this new ECF sigma factor could play a role in the transcriptional regulation of genes involved in motility behavior during both stages of the complex M. xanthus life cycle. PMID:9791117

  17. Processing of cell-surface signalling anti-sigma factors prior to signal recognition is a conserved autoproteolytic mechanism that produces two functional domains.

    PubMed

    Bastiaansen, Karlijn C; Otero-Asman, Joaquín R; Luirink, Joen; Bitter, Wilbert; Llamas, María A

    2015-09-01

    Cell-surface signalling (CSS) enables Gram-negative bacteria to transduce an environmental signal into a cytosolic response. This regulatory cascade involves an outer membrane receptor that transmits the signal to an anti-sigma factor in the cytoplasmic membrane, allowing the activation of an extracytoplasmic function (ECF) sigma factor. Recent studies have demonstrated that RseP-mediated proteolysis of the anti-sigma factors is key to σ(ECF) activation. Using the Pseudomonas aeruginosa FoxR anti-sigma factor, we show here that RseP is responsible for the generation of an N-terminal tail that likely contains pro-sigma activity. Furthermore, it has been reported previously that this anti-sigma factor is processed in two separate domains prior to signal recognition. Here, we demonstrate that this process is common in these types of proteins and that the processing event is probably due to autoproteolytic activity. The resulting domains interact and function together to transduce the CSS signal. However, our results also indicate that this processing event is not essential for activity. In fact, we have identified functional CSS anti-sigma factors that are not cleaved prior to signal perception. Together, our results indicate that CSS regulation can occur through both complete and initially processed anti-sigma factors. PMID:25581349

  18. Predicting strength and function for promoters of the Escherichia coli alternative sigma factor, sigmaE.

    PubMed

    Rhodius, Virgil A; Mutalik, Vivek K

    2010-02-16

    Sequenced bacterial genomes provide a wealth of information but little understanding of transcriptional regulatory circuits largely because accurate prediction of promoters is difficult. We examined two important issues for accurate promoter prediction: (1) the ability to predict promoter strength and (2) the sequence properties that distinguish between active and weak/inactive promoters. We addressed promoter prediction using natural core promoters recognized by the well-studied alternative sigma factor, Escherichia coli sigma(E), as a representative of group 4 sigmas, the largest sigma group. To evaluate the contribution of sequence to promoter strength and function, we used modular position weight matrix models comprised of each promoter motif and a penalty score for suboptimal motif location. We find that a combination of select modules is moderately predictive of promoter strength and that imposing minimal motif scores distinguished active from weak/inactive promoters. The combined -35/-10 score is the most important predictor of activity. Our models also identified key sequence features associated with active promoters. A conserved "AAC" motif in the -35 region is likely to be a general predictor of function for promoters recognized by group 4 sigmas. These results provide valuable insights into sequences that govern promoter strength, distinguish active and inactive promoters for the first time, and are applicable to both in vivo and in vitro measures of promoter strength. PMID:20133665

  19. Bacterial Sigma Factors and Anti-Sigma Factors: Structure, Function and Distribution

    PubMed Central

    Paget, Mark S.

    2015-01-01

    Sigma factors are multi-domain subunits of bacterial RNA polymerase (RNAP) that play critical roles in transcription initiation, including the recognition and opening of promoters as well as the initial steps in RNA synthesis. This review focuses on the structure and function of the major sigma-70 class that includes the housekeeping sigma factor (Group 1) that directs the bulk of transcription during active growth, and structurally-related alternative sigma factors (Groups 2–4) that control a wide variety of adaptive responses such as morphological development and the management of stress. A recurring theme in sigma factor control is their sequestration by anti-sigma factors that occlude their RNAP-binding determinants. Sigma factors are then released through a wide variety of mechanisms, often involving branched signal transduction pathways that allow the integration of distinct signals. Three major strategies for sigma release are discussed: regulated proteolysis, partner-switching, and direct sensing by the anti-sigma factor. PMID:26131973

  20. Multiple σEcfG and NepR Proteins Are Involved in the General Stress Response in Methylobacterium extorquens

    PubMed Central

    Francez-Charlot, Anne; Frunzke, Julia; Zingg, Judith; Kaczmarczyk, Andreas; Vorholt, Julia A.

    2016-01-01

    In Alphaproteobacteria, the general stress response (GSR) is controlled by a conserved partner switch composed of the sigma factor σEcfG, its anti-sigma factor NepR and the anti-sigma factor antagonist PhyR. Many species possess paralogues of one or several components of the system, but their roles remain largely elusive. Among Alphaproteobacteria that have been genome-sequenced so far, the genus Methylobacterium possesses the largest number of σEcfG proteins. Here, we analyzed the six σEcfG paralogues of Methylobacterium extorquens AM1. We show that these sigma factors are not truly redundant, but instead exhibit major and minor contributions to stress resistance and GSR target gene expression. We identify distinct levels of regulation for the different sigma factors, as well as two NepR paralogues that interact with PhyR. Our results suggest that in M. extorquens AM1, ecfG and nepR paralogues have diverged in order to assume new roles that might allow integration of positive and negative feedback loops in the regulatory system. Comparison of the core elements of the GSR regulatory network in Methylobacterium species provides evidence for high plasticity and rapid evolution of the GSR core network in this genus. PMID:27028226

  1. Multiple σEcfG and NepR Proteins Are Involved in the General Stress Response in Methylobacterium extorquens.

    PubMed

    Francez-Charlot, Anne; Frunzke, Julia; Zingg, Judith; Kaczmarczyk, Andreas; Vorholt, Julia A

    2016-01-01

    In Alphaproteobacteria, the general stress response (GSR) is controlled by a conserved partner switch composed of the sigma factor σEcfG, its anti-sigma factor NepR and the anti-sigma factor antagonist PhyR. Many species possess paralogues of one or several components of the system, but their roles remain largely elusive. Among Alphaproteobacteria that have been genome-sequenced so far, the genus Methylobacterium possesses the largest number of σEcfG proteins. Here, we analyzed the six σEcfG paralogues of Methylobacterium extorquens AM1. We show that these sigma factors are not truly redundant, but instead exhibit major and minor contributions to stress resistance and GSR target gene expression. We identify distinct levels of regulation for the different sigma factors, as well as two NepR paralogues that interact with PhyR. Our results suggest that in M. extorquens AM1, ecfG and nepR paralogues have diverged in order to assume new roles that might allow integration of positive and negative feedback loops in the regulatory system. Comparison of the core elements of the GSR regulatory network in Methylobacterium species provides evidence for high plasticity and rapid evolution of the GSR core network in this genus. PMID:27028226

  2. Characterization of the extrachromosomal function (ECF) sigma factors of Arcobacter butzleri

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Campylobacter jejuni is the most commonly reported cause of bacterial foodborne illness in North America. C. jejuni decorates its surface polysaccharides with a variety of variable phosphorylated structures, including O-methyl phosphoramidate (MeOPN) modifications on the capsular polysaccharide. Alt...

  3. Characterization of Promoter Motifs Regulated by ECF Sigma Factors of Pseudomonas syringae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pseudomanads are renowned for their capacity to adapt to diverse environments, a fact that is reflected by the proportion of their genomes dedicated to encoding transcription regulators. Members of the Pseudomonas genus include species that are adapted to pathogenic and symbiotic lifestyles in asso...

  4. Stress Response in Rhodopseudomonas palustris CGA010 is Mediated by an Extracytoplasmic Function Sigma Factor

    DOE PAGESBeta

    Allen, Michael S; Hurst, Gregory; Lu, Tse-Yuan S; Leslie, Perry M; Pan, Chongle; Lankford, Patricia K; Pelletier, Dale A

    2015-01-01

    Abstract Little is known about the roles of the 16 extracytoplasmic function (ECF) sigma factors in Rhodopseudomonas palustris gene regulation. To begin to address this deficiency, the whole proteome of R. palustris CGA010 was analyzed by tandem mass spectrometry from cultures episomally expressing the ECF RPA4225. Among the proteins with the greatest increase in abundance were the catalase KatE, trehalose synthase, a DPS-like protein, and several regulatory proteins. Alignment of the cognate promoter regions driving expression of several up-regulated proteins revealed a conserved binding motif in the -35 and -10 regions with the consensus sequence GGAAC-18N-TT. Analysis of the genomemore » revealed the occurrence of this motif in the promoters of over 150 genes, including general stress proteins, ATP-dependent DNA ligase, two Ku-domain-containing proteins, and the heat-shock m factor rpoH. Additionally, the putative anti- m factor RPA4224, whose gene is contained in the same predicted operon as RPA4225, was identified as interacting directly with the predicted response regulator RPA4223 by mass spectrometry of affinity isolated protein complexes. Furthermore, another protein containing a cytoplasmic histidine kinase domain is located immediately upstream of RPA4225. The genomic organization of homologues for these four genes is conserved in several other strains of R. palustris as well as in closely related \\-proteobacteria. Taken together, these data suggest that ECF RPA4225 controls a global stress regulon that is in turn controlled via a phosphorelay mechanism involving a histidine kinase sensor, a response regulator, and an anti m factor that are conserved among several members of \\-proteobacteria.« less

  5. The Putative Lactococcal Extracytoplasmic Function Anti-Sigma Factor Llmg2447 Determines Resistance to the Cell Wall-Active Bacteriocin Lcn972

    PubMed Central

    Roces, Clara; Pérez, Verónica; Campelo, Ana B.; Blanco, Diego; Kok, Jan; Kuipers, Oscar P.; Rodríguez, Ana

    2012-01-01

    Lactococcin 972 (Lcn972) is a cell wall-active bacteriocin that inhibits cell wall biosynthesis in Lactococcus lactis. In this work, the transcriptomes of the Lcn972-resistant (Lcnr) mutant L. lactis D1 and its parent strain were compared to identify factors involved in Lcn972 resistance. Upregulated genes included members of the cell envelope stress (CesSR) regulon, the penicillin-binding protein pbpX gene and gene llmg2447, which may encode a putative extracytoplasmic function (ECF) anti-sigma factor. The gene llmg2447 is located downstream of the nonfunctional ECF gene sigXpseudo. Nisin-controlled expression of llmg2447 led to high Lcn972 resistance in L. lactis, with no cross-resistance to other cell wall-active antimicrobials. Upregulation of llmg2447 in L. lactis D1 (Lcnr) was linked to the integration of insertion element IS981 into the llmg2447 promoter region, replacing the native −35 box and activating the otherwise silent promoter P2447. This is the first example of an orphan ECF anti-sigma factor involved in bacteriocin resistance. This new role in neutralizing cell wall-active compounds (e.g., Lcn972) could have evolved from a putative primary function of Llmg2447 in sensing cell envelope stress. PMID:22890757

  6. Isolation and characterization of the Bacillus subtilis sigma 28 factor.

    PubMed Central

    Helmann, J D; Masiarz, F R; Chamberlin, M J

    1988-01-01

    RNA polymerase preparations isolated from vegetatively growing Bacillus subtilis cells contain the core subunits beta, beta', and alpha, together with multiple sigma factors and other core-associated polypeptides such as delta, omega 1, and omega 2. We have developed an improved, large-scale purification procedure that yields RNA polymerase fractions enriched in both the sigma 28 and delta proteins. These fractions have been used to isolate sigma 28 protein for biochemical characterization and for preparation of highly specific anti-sigma 28 antisera. The amino acid composition of purified sigma 28 protein and the amino acid sequences of tryptic peptide fragments have been determined. Anti-sigma 28 antisera specifically inhibit transcription by the purified sigma 28 -dependent RNA polymerase, yet do not affect transcription by sigma 43 -dependent RNA polymerase. Immunochemical analysis confirms that the sigma 28 protein copurifies with total RNA polymerase activity through the majority of the purification procedure and allows the steps when sigma 28 protein is lost to be identified and optimized. Immunochemical techniques have also been used to monitor the structure and abundance of the sigma 28 protein in vivo. A single form of antibody-reactive protein was detected by two-dimensional gel electrophoresis-isoelectric focusing. Its abundance corresponds to a maximal content of 220 molecules of sigma 28 per B. subtilis cell during late-logarithmic-phase growth. Images PMID:3127378

  7. Interaction of sigma factor sigmaN with Escherichia coli RNA polymerase core enzyme.

    PubMed Central

    Scott, D J; Ferguson, A L; Gallegos, M T; Pitt, M; Buck, M; Hoggett, J G

    2000-01-01

    The equilibrium binding and kinetics of assembly of the DNA-dependent RNA polymerase (RNAP) sigma(N)-holoenzyme has been investigated using biosynthetically labelled 7-azatryptophyl- (7AW)sigma(N). The spectroscopic properties of such 7AW proteins allows their absorbance and fluorescence to be monitored selectively, even in the presence of high concentrations of other tryptophan-containing proteins. The 7AWsigma(N) retained its biological activity in stimulating transcription from sigma(N)-specific promoters, and in in vitro gel electrophoresis assays of binding to core RNAP from Escherichia coli. Furthermore, five Trp-->Ala single mutants of sigma(N) were shown to support growth under conditions of nitrogen limitation, and showed comparable efficiency in activating the sigma(N)-dependent nifH promoter in vivo, indicating that none of the tryptophan residues were essential for activity. The equilibrium binding of 7AWsigma(N) to core RNAP was examined by analytical ultracentrifugation. In sedimentation equilibrium experiments, absorbance data at 315 nm (which reports selectively on the distribution of free and bound 7AWsigma(N)) established that a 1:1 complex was formed, with a dissociation constant lower than 2 microM. The kinetics of the interaction between 7AWsigma(N) and core RNAP was investigated using stopped-flow spectrofluorimetry. A biphasic decrease in fluorescence intensity was observed when samples were excited at 280 nm, whereas only the slower of the two phases was observed at 315 nm. The kinetic data were analysed in terms of a mechanism in which a fast bimolecular association of sigma(N) with core RNAP is followed by a relatively slow isomerization step. The consequences of these findings on the competition between sigma(N) and the major sigma factor, sigma(70), in Escherichia coli are discussed. PMID:11085949

  8. Interaction of sigma factor sigmaN with Escherichia coli RNA polymerase core enzyme.

    PubMed

    Scott, D J; Ferguson, A L; Gallegos, M T; Pitt, M; Buck, M; Hoggett, J G

    2000-12-01

    The equilibrium binding and kinetics of assembly of the DNA-dependent RNA polymerase (RNAP) sigma(N)-holoenzyme has been investigated using biosynthetically labelled 7-azatryptophyl- (7AW)sigma(N). The spectroscopic properties of such 7AW proteins allows their absorbance and fluorescence to be monitored selectively, even in the presence of high concentrations of other tryptophan-containing proteins. The 7AWsigma(N) retained its biological activity in stimulating transcription from sigma(N)-specific promoters, and in in vitro gel electrophoresis assays of binding to core RNAP from Escherichia coli. Furthermore, five Trp-->Ala single mutants of sigma(N) were shown to support growth under conditions of nitrogen limitation, and showed comparable efficiency in activating the sigma(N)-dependent nifH promoter in vivo, indicating that none of the tryptophan residues were essential for activity. The equilibrium binding of 7AWsigma(N) to core RNAP was examined by analytical ultracentrifugation. In sedimentation equilibrium experiments, absorbance data at 315 nm (which reports selectively on the distribution of free and bound 7AWsigma(N)) established that a 1:1 complex was formed, with a dissociation constant lower than 2 microM. The kinetics of the interaction between 7AWsigma(N) and core RNAP was investigated using stopped-flow spectrofluorimetry. A biphasic decrease in fluorescence intensity was observed when samples were excited at 280 nm, whereas only the slower of the two phases was observed at 315 nm. The kinetic data were analysed in terms of a mechanism in which a fast bimolecular association of sigma(N) with core RNAP is followed by a relatively slow isomerization step. The consequences of these findings on the competition between sigma(N) and the major sigma factor, sigma(70), in Escherichia coli are discussed. PMID:11085949

  9. The general stress response factor EcfG regulates expression of the C-2 hopanoid methylase HpnP in Rhodopseudomonas palustris TIE-1.

    PubMed

    Kulkarni, Gargi; Wu, Chia-Hung; Newman, Dianne K

    2013-06-01

    Lipid molecules preserved in sedimentary rocks facilitate the reconstruction of events that have shaped the evolution of the Earth's biosphere. A key limitation for the interpretation of many of these molecular fossils is that their biological roles are still poorly understood. Here, we use Rhodopseudomonas palustris TIE-1 to identify factors that induce biosynthesis of 2-methyl hopanoids (2-MeBHPs), progenitors of 2-methyl hopanes, one of the most abundant biomarkers in the rock record. This is the first dissection of the regulation of hpnP, the gene encoding the C-2 hopanoid methylase, at the molecular level. We demonstrate that EcfG, the general stress response factor of alphaproteobacteria, regulates expression of hpnP under a variety of challenges, including high temperature, pH stress, and presence of nonionic osmolytes. Although higher hpnP transcription levels did not always result in higher amounts of total methylated hopanoids, the fraction of a particular kind of hopanoid, 2-methyl bacteriohopanetetrol, was consistently higher in the presence of most stressors in the wild type, but not in the ΔecfG mutant, supporting a beneficial role for 2-MeBHPs in stress tolerance. The ΔhpnP mutant, however, did not exhibit a growth defect under the stress conditions tested except in acidic medium. This indicates that the inability to make 2-MeBHPs under most of these conditions can readily be compensated. Although stress is necessary to regulate 2-MeBHP production, the specific conditions under which 2-MeBHP biosynthesis is essential remain to be determined. PMID:23524612

  10. Functional modules of sigma factor regulons guarantee adaptability and evolvability

    PubMed Central

    Binder, Sebastian C.; Eckweiler, Denitsa; Schulz, Sebastian; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Häussler, Susanne; Meyer-Hermann, Michael

    2016-01-01

    The focus of modern molecular biology turns from assigning functions to individual genes towards understanding the expression and regulation of complex sets of molecules. Here, we provide evidence that alternative sigma factor regulons in the pathogen Pseudomonas aeruginosa largely represent insulated functional modules which provide a critical level of biological organization involved in general adaptation and survival processes. Analysis of the operational state of the sigma factor network revealed that transcription factors functionally couple the sigma factor regulons and significantly modulate the transcription levels in the face of challenging environments. The threshold quality of newly evolved transcription factors was reached faster and more robustly in in silico testing when the structural organization of sigma factor networks was taken into account. These results indicate that the modular structures of alternative sigma factor regulons provide P. aeruginosa with a robust framework to function adequately in its environment and at the same time facilitate evolutionary change. Our data support the view that widespread modularity guarantees robustness of biological networks and is a key driver of evolvability. PMID:26915971

  11. Functional modules of sigma factor regulons guarantee adaptability and evolvability.

    PubMed

    Binder, Sebastian C; Eckweiler, Denitsa; Schulz, Sebastian; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Häussler, Susanne; Meyer-Hermann, Michael

    2016-01-01

    The focus of modern molecular biology turns from assigning functions to individual genes towards understanding the expression and regulation of complex sets of molecules. Here, we provide evidence that alternative sigma factor regulons in the pathogen Pseudomonas aeruginosa largely represent insulated functional modules which provide a critical level of biological organization involved in general adaptation and survival processes. Analysis of the operational state of the sigma factor network revealed that transcription factors functionally couple the sigma factor regulons and significantly modulate the transcription levels in the face of challenging environments. The threshold quality of newly evolved transcription factors was reached faster and more robustly in in silico testing when the structural organization of sigma factor networks was taken into account. These results indicate that the modular structures of alternative sigma factor regulons provide P. aeruginosa with a robust framework to function adequately in its environment and at the same time facilitate evolutionary change. Our data support the view that widespread modularity guarantees robustness of biological networks and is a key driver of evolvability. PMID:26915971

  12. Functional modules of sigma factor regulons guarantee adaptability and evolvability

    NASA Astrophysics Data System (ADS)

    Binder, Sebastian C.; Eckweiler, Denitsa; Schulz, Sebastian; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Häussler, Susanne; Meyer-Hermann, Michael

    2016-02-01

    The focus of modern molecular biology turns from assigning functions to individual genes towards understanding the expression and regulation of complex sets of molecules. Here, we provide evidence that alternative sigma factor regulons in the pathogen Pseudomonas aeruginosa largely represent insulated functional modules which provide a critical level of biological organization involved in general adaptation and survival processes. Analysis of the operational state of the sigma factor network revealed that transcription factors functionally couple the sigma factor regulons and significantly modulate the transcription levels in the face of challenging environments. The threshold quality of newly evolved transcription factors was reached faster and more robustly in in silico testing when the structural organization of sigma factor networks was taken into account. These results indicate that the modular structures of alternative sigma factor regulons provide P. aeruginosa with a robust framework to function adequately in its environment and at the same time facilitate evolutionary change. Our data support the view that widespread modularity guarantees robustness of biological networks and is a key driver of evolvability.

  13. Evidence of a Bacterial Receptor for Lysozyme: Binding of Lysozyme to the Anti-σ Factor RsiV Controls Activation of the ECF σ Factor σV

    PubMed Central

    Sepúlveda, Carolina; Houtman, Jon C.; Forest, Katrina T.; Ellermeier, Craig D.

    2014-01-01

    σ factors endow RNA polymerase with promoter specificity in bacteria. Extra-Cytoplasmic Function (ECF) σ factors represent the largest and most diverse family of σ factors. Most ECF σ factors must be activated in response to an external signal. One mechanism of activation is the stepwise proteolytic destruction of an anti-σ factor via Regulated Intramembrane Proteolysis (RIP). In most cases, the site-1 protease required to initiate the RIP process directly senses the signal. Here we report a new mechanism in which the anti-σ factor rather than the site-1 protease is the sensor. We provide evidence suggesting that the anti-σ factor RsiV is the bacterial receptor for the innate immune defense enzyme, lysozyme. The site-1 cleavage site is similar to the recognition site of signal peptidase and cleavage at this site is required for σV activation in Bacillus subtilis. We reconstitute site-1 cleavage in vitro and demonstrate that it requires both signal peptidase and lysozyme. We demonstrate that the anti-σ factor RsiV directly binds to lysozyme and muramidase activity is not required for σV activation. We propose a model in which the binding of lysozyme to RsiV activates RsiV for signal peptidase cleavage at site-1, initiating proteolytic destruction of RsiV and activation of σV. This suggests a novel mechanism in which conformational change in a substrate controls the cleavage susceptibility for signal peptidase. Thus, unlike other ECF σ factors which require regulated intramembrane proteolysis for activation, the sensor for σV activation is not the site-1 protease but the anti-σ factor. PMID:25275625

  14. Evidence of a bacterial receptor for lysozyme: binding of lysozyme to the anti-σ factor RsiV controls activation of the ecf σ factor σV.

    PubMed

    Hastie, Jessica L; Williams, Kyle B; Sepúlveda, Carolina; Houtman, Jon C; Forest, Katrina T; Ellermeier, Craig D

    2014-10-01

    σ factors endow RNA polymerase with promoter specificity in bacteria. Extra-Cytoplasmic Function (ECF) σ factors represent the largest and most diverse family of σ factors. Most ECF σ factors must be activated in response to an external signal. One mechanism of activation is the stepwise proteolytic destruction of an anti-σ factor via Regulated Intramembrane Proteolysis (RIP). In most cases, the site-1 protease required to initiate the RIP process directly senses the signal. Here we report a new mechanism in which the anti-σ factor rather than the site-1 protease is the sensor. We provide evidence suggesting that the anti-σ factor RsiV is the bacterial receptor for the innate immune defense enzyme, lysozyme. The site-1 cleavage site is similar to the recognition site of signal peptidase and cleavage at this site is required for σV activation in Bacillus subtilis. We reconstitute site-1 cleavage in vitro and demonstrate that it requires both signal peptidase and lysozyme. We demonstrate that the anti-σ factor RsiV directly binds to lysozyme and muramidase activity is not required for σV activation. We propose a model in which the binding of lysozyme to RsiV activates RsiV for signal peptidase cleavage at site-1, initiating proteolytic destruction of RsiV and activation of σV. This suggests a novel mechanism in which conformational change in a substrate controls the cleavage susceptibility for signal peptidase. Thus, unlike other ECF σ factors which require regulated intramembrane proteolysis for activation, the sensor for σV activation is not the site-1 protease but the anti-σ factor. PMID:25275625

  15. Virulence properties of Pseudomonas aeruginosa lacking the extreme-stress sigma factor AlgU (sigmaE).

    PubMed

    Yu, H; Boucher, J C; Hibler, N S; Deretic, V

    1996-07-01

    A discerning feature of Pseudomonas aeruginosa strains causing chronic endobronchial infections in cystic fibrosis is their conversion into the mucoid, exopolysaccharide alginate-overproducing phenotype. This morphologically prominent change is caused by mutations which upregulate AlgU (sigma(E)), a novel extreme-stress sigma factor with functional equivalents in gram-negative organisms. In this work, we investigated the role of algU in P. aeruginosa sensitivity to reactive oxygen intermediates, killing by phagocytic cells, and systemic virulence of this bacterium. Inactivation of algU in P. aeruginosa PA01 increased its susceptibility to killing by chemically or enzymatically generated halogenated reactive oxygen intermediates and reduced its survival in bactericidal assays with J774 murine macrophages and human neutrophils. Surprisingly, inactivation of algU caused increased systemic virulence of P. aeruginosa in mouse models of acute infection. The increased lethality of the algU-deficient strain was also observed in the endotoxin-resistant C3H/HeJ mice. Only minor differences between algU+ and algU mutant cells in their sensitivity to human serum were observed, and no differences in their lipopolysaccharide profiles were detected. Intriguingly, while inactivation of algU downregulated five polypeptides it also upregulated the expression of seven polypeptides as determined by two-dimensional gel analyses, suggesting that algU plays both a positive and a negative role in gene expression in P. aeruginosa. While the observation that algU inactivation increases systemic virulence in P. aeruginosa requires further explanation, this phenomenon contrasts with the apparent selection for strains with upregulated AlgU during colonization of the cystic fibrosis lung and suggests opposing roles for this system in chronic and acute infections. PMID:8698507

  16. Whole-genome phylogenies of the family Bacillaceae and expansion of the sigma factor gene family in the Bacillus cereus species-group

    PubMed Central

    2011-01-01

    occurred within the extracytoplasmic function (ECF) sigma factor genes, while the primary alternative (PA) sigma factor genes are, in general, highly conserved with those found in B. subtilis. Divergence of the sigma-controlled transcriptional regulons among various members of the Bc species-group likely has a major role in explaining the diversity of phenotypic characteristics seen in members of the Bc species-group. PMID:21864360

  17. Eep confers lysozyme resistance to enterococcus faecalis via the activation of the extracytoplasmic function sigma factor SigV.

    PubMed

    Varahan, Sriram; Iyer, Vijayalakshmi S; Moore, William T; Hancock, Lynn E

    2013-07-01

    Enterococcus faecalis is a commensal bacterium found in the gastrointestinal tract of most mammals, including humans, and is one of the leading causes of nosocomial infections. One of the hallmarks of E. faecalis pathogenesis is its unusual ability to tolerate high concentrations of lysozyme, which is an important innate immune component of the host. Previous studies have shown that the presence of lysozyme leads to the activation of SigV, an extracytoplasmic function (ECF) sigma factor in E. faecalis, and that the deletion of sigV increases the susceptibility of the bacterium toward lysozyme. Here, we describe the contribution of Eep, a membrane-bound zinc metalloprotease, to the activation of SigV under lysozyme stress by its effects on the stability of the anti-sigma factor RsiV. We demonstrate that the Δeep mutant phenocopies the ΔsigV mutant in lysozyme, heat, ethanol, and acid stress susceptibility. We also show, using an immunoblot analysis, that in an eep deletion mutant, the anti-sigma factor RsiV is only partially degraded after lysozyme exposure, suggesting that RsiV is processed by unknown protease(s) prior to the action of Eep. An additional observation is that the deletion of rsiV, which results in constitutive SigV expression, leads to chaining of cells, suggesting that SigV might be involved in regulating cell wall-modifying enzymes important in cell wall turnover. We also demonstrate that, in the absence of eep or sigV, enterococci bind significantly more lysozyme, providing a plausible explanation for the increased sensitivity of these mutants toward lysozyme. PMID:23645601

  18. Reconstruction and topological characterization of the sigma factor regulatory network of Mycobacterium tuberculosis.

    PubMed

    Chauhan, Rinki; Ravi, Janani; Datta, Pratik; Chen, Tianlong; Schnappinger, Dirk; Bassler, Kevin E; Balázsi, Gábor; Gennaro, Maria Laura

    2016-01-01

    Accessory sigma factors, which reprogram RNA polymerase to transcribe specific gene sets, activate bacterial adaptive responses to noxious environments. Here we reconstruct the complete sigma factor regulatory network of the human pathogen Mycobacterium tuberculosis by an integrated approach. The approach combines identification of direct regulatory interactions between M. tuberculosis sigma factors in an E. coli model system, validation of selected links in M. tuberculosis, and extensive literature review. The resulting network comprises 41 direct interactions among all 13 sigma factors. Analysis of network topology reveals (i) a three-tiered hierarchy initiating at master regulators, (ii) high connectivity and (iii) distinct communities containing multiple sigma factors. These topological features are likely associated with multi-layer signal processing and specialized stress responses involving multiple sigma factors. Moreover, the identification of overrepresented network motifs, such as autoregulation and coregulation of sigma and anti-sigma factor pairs, provides structural information that is relevant for studies of network dynamics. PMID:27029515

  19. Reconstruction and topological characterization of the sigma factor regulatory network of Mycobacterium tuberculosis

    PubMed Central

    Chauhan, Rinki; Ravi, Janani; Datta, Pratik; Chen, Tianlong; Schnappinger, Dirk; Bassler, Kevin E.; Balázsi, Gábor; Gennaro, Maria Laura

    2016-01-01

    Accessory sigma factors, which reprogram RNA polymerase to transcribe specific gene sets, activate bacterial adaptive responses to noxious environments. Here we reconstruct the complete sigma factor regulatory network of the human pathogen Mycobacterium tuberculosis by an integrated approach. The approach combines identification of direct regulatory interactions between M. tuberculosis sigma factors in an E. coli model system, validation of selected links in M. tuberculosis, and extensive literature review. The resulting network comprises 41 direct interactions among all 13 sigma factors. Analysis of network topology reveals (i) a three-tiered hierarchy initiating at master regulators, (ii) high connectivity and (iii) distinct communities containing multiple sigma factors. These topological features are likely associated with multi-layer signal processing and specialized stress responses involving multiple sigma factors. Moreover, the identification of overrepresented network motifs, such as autoregulation and coregulation of sigma and anti-sigma factor pairs, provides structural information that is relevant for studies of network dynamics. PMID:27029515

  20. Exploring the role of sigma factor gene expression on production by Corynebacterium glutamicum: sigma factor H and FMN as example

    PubMed Central

    Taniguchi, Hironori; Wendisch, Volker F.

    2015-01-01

    Bacteria are known to cope with environmental changes by using alternative sigma factors binding to RNA polymerase core enzyme. Sigma factor is one of the targets to modify transcription regulation in bacteria and to influence production capacities. In this study, the effect of overexpressing each annotated sigma factor gene in Corynebacterium glutamicum WT was assayed using an IPTG inducible plasmid system and different IPTG concentrations. It was revealed that growth was severely decreased when sigD or sigH were overexpressed with IPTG concentrations higher than 50 μM. Overexpression of sigH led to an obvious phenotypic change, a yellow-colored supernatant. High performance liquid chromatography analysis revealed that riboflavin was excreted to the medium when sigH was overexpressed and DNA microarray analysis confirmed increased expression of riboflavin biosynthesis genes. In addition, genes for enzymes related to the pentose phosphate pathway and for enzymes dependent on flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), or NADPH as cofactor were upregulated when sigH was overexpressed. To test if sigH overexpression can be exploited for production of riboflavin-derived FMN or FAD, the endogenous gene for bifunctional riboflavin kinase/FMN adenyltransferase was co-expressed with sigH from a plasmid. Balanced expression of sigH and ribF improved accumulation of riboflavin (19.8 ± 0.3 μM) and allowed for its conversion to FMN (33.1 ± 1.8 μM) in the supernatant. While a proof-of-concept was reached, conversion was not complete and titers were not high. This study revealed that inducible and gradable overexpression of sigma factor genes is an interesting approach to switch gene expression profiles and to discover untapped potential of bacteria for chemical production. PMID:26257719

  1. In depth analysis of the mechanism of action of metal-dependent sigma factors: characterization of CorE2 from Myxococcus xanthus

    PubMed Central

    Marcos-Torres, Francisco Javier; Pérez, Juana; Gómez-Santos, Nuria; Moraleda-Muñoz, Aurelio; Muñoz-Dorado, José

    2016-01-01

    Extracytoplasmic function sigma factors represent the third pillar of signal-transduction mechanisms in bacteria. The variety of stimuli they recognize and mechanisms of action they use have allowed their classification into more than 50 groups. We have characterized CorE2 from Myxococcus xanthus, which belongs to group ECF44 and upregulates the expression of two genes when it is activated by cadmium and zinc. Sigma factors of this group contain a Cys-rich domain (CRD) at the C terminus which is essential for detecting metals. Point mutations at the six Cys residues of the CRD have revealed the contribution of each residue to CorE2 activity. Some of them are essential, while others are either dispensable or their mutations only slightly affect the activity of the protein. However, importantly, mutation of Cys174 completely shifts the specificity of CorE2 from cadmium to copper, indicating that the Cys arrangement of the CRD determines the metal specificity. Moreover, the conserved CxC motif located between the σ2 domain and the σ4.2 region has also been found to be essential for activity. The results presented here contribute to our understanding of the mechanism of action of metal-dependent sigma factors and help to define new common features of the members of this group of regulators. PMID:26951374

  2. Evidence that sigma factors are components of chloroplast RNA polymerase.

    PubMed Central

    Troxler, R F; Zhang, F; Hu, J; Bogorad, L

    1994-01-01

    Plastid genes are transcribed by DNA-dependent RNA polymerase(s), which have been incompletely characterized and have been examined in a limited number of species. Plastid genomes contain rpoA, rpoB, rpoC1, and rpoC2 coding for alpha, beta, beta', and beta" RNA polymerase subunits that are homologous to the alpha, beta, and beta' subunits that constitute the core moiety of RNA polymerase in bacteria. However, genes with homology to sigma subunits in bacteria have not been found in plastid genomes. An antibody directed against the principal sigma subunit of RNA polymerase from the cyanobacterium Anabaena sp. PCC 7120 was used to probe western blots of purified chloroplast RNA polymerase from maize, rice, Chlamydomonas reinhardtii, and Cyanidium caldarium. Chloroplast RNA polymerase from maize and rice contained an immunoreactive 64-kD protein. Chloroplast RNA polymerase from C. reinhardtii contained immunoreactive 100- and 82-kD proteins, and chloroplast RNA polymerase from C. caldarium contained an immunoreactive 32-kD protein. The elution profile of enzyme activity of both algal chloroplast RNA polymerases coeluted from DEAE with the respective immunoreactive proteins, indicating that they are components of the enzyme. These results provide immunological evidence for sigma-like factors in chloroplast RNA polymerase in higher plants and algae. PMID:8159791

  3. Characterizing the interplay betwen mulitple levels of organization within bacterial sigma factor regulatory networks

    SciTech Connect

    Yu, Qiu; Nagarajan, Harish; Embree, Mallory; Shieu, Wendy; Abate, Elisa; Juarez, Katy; Cho, Byung-Kwan; Elkins, James G; Nevin, Kelly P.; Barrett, Christian; Lovley, Derek; Palsson, Bernhard O.; Zengler, Karsten

    2013-01-01

    Bacteria contain multiple sigma factors, each targeting diverse, but often overlapping sets of promoters, thereby forming a complex network. The layout and deployment of such a sigma factor network directly impacts global transcriptional regulation and ultimately dictates the phenotype. Here we integrate multi-omic data sets to determine the topology, the operational, and functional states of the sigma factor network in Geobacter sulfurreducens, revealing a unique network topology of interacting sigma factors. Analysis of the operational state of the sigma factor network shows a highly modular structure with sN being the major regulator of energy metabolism. Surprisingly, the functional state of the network during the two most divergent growth conditions is nearly static, with sigma factor binding profiles almost invariant to environmental stimuli. This first comprehensive elucidation of the interplay between different levels of the sigma factor network organization is fundamental to characterize transcriptional regulatory mechanisms in bacteria.

  4. Transcription of the oprF Gene of Pseudomonas aeruginosa Is Dependent Mainly on the SigX Sigma Factor and Is Sucrose Induced

    PubMed Central

    Bouffartigues, Emeline; Gicquel, Gwendoline; Bazire, Alexis; Bains, Manjeet; Maillot, Olivier; Vieillard, Julien; Feuilloley, Marc G. J.; Orange, Nicole; Hancock, R. E. W.; Dufour, Alain

    2012-01-01

    The OprF porin is the major outer membrane protein of Pseudomonas aeruginosa. OprF is involved in several crucial functions, including cell structure, outer membrane permeability, environmental sensing, and virulence. The oprF gene is preceded by the sigX gene, which encodes the poorly studied extracytoplasmic function (ECF) sigma factor SigX. Three oprF promoters were previously identified. Two intertwined promoters dependent on σ70 and SigX are located in the sigX-oprF intergenic region, whereas a promoter dependent on the ECF AlgU lies within the sigX gene. An additional promoter was found in the cmpX-sigX intergenic region. In this study, we dissected the contribution of each promoter region and of each sigma factor to oprF transcription using transcriptional fusions. In Luria-Bertani (LB) medium, the oprF-proximal region (sigX-oprF intergenic region) accounted for about 80% of the oprF transcription, whereas the AlgU-dependent promoter had marginal activity. Using the sigX mutant PAOSX, we observed that the SigX-dependent promoter was largely predominant over the σ70-dependent promoter. oprF transcription was increased in response to low NaCl or high sucrose concentrations, and this induced transcription was strongly impaired in the absence of SigX. The lack of OprF itself increased oprF transcription. Since these conditions led to cell wall alterations, oprF transcription could be activated by signals triggered by perturbation of the cell envelope. PMID:22685281

  5. Induction of a stable sigma factor SigR by translation-inhibiting antibiotics confers resistance to antibiotics

    PubMed Central

    Yoo, Ji-Sun; Oh, Gyeong-Seok; Ryoo, Sungweon; Roe, Jung-Hye

    2016-01-01

    Antibiotic-producing streptomycetes are rich sources of resistance mechanisms against endogenous and exogenous antibiotics. An ECF sigma factor σR (SigR) is known to govern the thiol-oxidative stress response in Streptomyces coelicolor. Amplification of this response is achieved by producing an unstable isoform of σR called σR′. In this work, we present evidence that antibiotics induce the SigR regulon via a redox-independent pathway, leading to antibiotic resistance. The translation-inhibiting antibiotics enhanced the synthesis of stable σR, eliciting a prolonged response. WblC/WhiB7, a WhiB-like DNA-binding protein, is responsible for inducing sigRp1 transcripts encoding the stable σR. The amount of WblC protein and its binding to the sigRp1 promoter in vivo increased upon antibiotic treatment. A similar phenomenon appears to exist in Mycobacterium tuberculosis as well. These findings reveal a novel antibiotic-induced resistance mechanism conserved among actinomycetes, and also give an explicit example of overlap in cellular damage and defense mechanisms between thiol-oxidative and anti- translational stresses. PMID:27346454

  6. Identification of subunits of gonococcal RNA polymerase by immunoblot analysis: evidence for multiple sigma factors.

    PubMed Central

    Klimpel, K W; Lesley, S A; Clark, V L

    1989-01-01

    Heparin-agarose and single-stranded DNA-cellulose chromatography were used to purify RNA polymerase 25-fold from Neisseria gonorrhoeae, and the activity of the polymerase was characterized in altered assay systems. The core subunits (beta, beta', and alpha) were tentatively identified as major proteins copurifying with polymerase activity. The identification of the core subunits was confirmed by Western (immunoblot) analysis with polyclonal antisera to Escherichia coli core RNA polymerase. Gonococcal sigma factor heterogeneity was examined by Western blot analysis with polyclonal antiserum to the major E. coli sigma factor, sigma 70, to the E. coli heat shock sigma factor, sigma 32, and with a monoclonal antiserum to Salmonella typhimurium NtrA (sigma 54). Purified RNA polymerase and whole-cell extracts from type 1, type 4, heat-shocked, and anaerobically grown gonococci were examined. Four putative gonococcal sigma factors were detected in purified RNA polymerase preparations and in whole-cell extracts from all cell types. Two of these bands appeared as a doublet, which had an estimated Mr of 80,000. A single lower-Mr band, estimated to be 40,000, was also present. All three of these bands reacted with antisera to E. coli sigma 70 and to E. coli sigma 32. A fourth gonococcal protein reacted solely with a highly specific monoclonal antibody to sigma 54 and had an Mr of 90,000. We conclude that N. gonorrhoeae may contain multiple sigma factors, which it may use to regulate gene expression. Images PMID:2472377

  7. Isolation and characterization of Escherichia coli mutants that lack the heat shock sigma factor sigma 32.

    PubMed Central

    Zhou, Y N; Kusukawa, N; Erickson, J W; Gross, C A; Yura, T

    1988-01-01

    The product of the Escherichia coli rpoH (htpR) gene, sigma 32, is required for heat-inducible transcription of the heat shock genes. Previous studies on the role of sigma 32 in growth at low temperature and in gene expression involved the use of nonsense and missense rpoH mutations and have led to ambiguous or conflicting results. To clarify the role of sigma 32 in cell physiology, we have constructed loss-of-function insertion and deletion mutations in rpoH. Strains lacking sigma 32 are extremely temperature sensitive and grow only at temperatures less than or equal to 20 degrees C. There is no transcription from the heat shock promoters preceding the htpG gene or the groESL and dnaKJ operons; however, several heat shock proteins are produced in the mutants. GroEL protein is present in the rpoH null mutants, but its synthesis is not inducible by a shift to high temperature. The low-level synthesis of GroEL results from transcription initiation at a minor sigma 70-controlled promoter for the groE operon. DnaK protein synthesis cannot be detected at low temperature, but can be detected after a shift to 42 degrees C. The mechanism of this heat-inducible synthesis is not known. We conclude that sigma 32 is required for cell growth at temperatures above 20 degrees C and is required for transcription from the heat shock promoters. Several heat shock proteins are synthesized in the absence of sigma 32, indicating that there are additional mechanisms controlling the synthesis of some heat shock proteins. Images PMID:2900239

  8. Genome-wide analysis of the general stress response network in Escherichia coli: sigmaS-dependent genes, promoters, and sigma factor selectivity.

    PubMed

    Weber, Harald; Polen, Tino; Heuveling, Johanna; Wendisch, Volker F; Hengge, Regine

    2005-03-01

    The sigmaS (or RpoS) subunit of RNA polymerase is the master regulator of the general stress response in Escherichia coli. While nearly absent in rapidly growing cells, sigmaS is strongly induced during entry into stationary phase and/or many other stress conditions and is essential for the expression of multiple stress resistances. Genome-wide expression profiling data presented here indicate that up to 10% of the E. coli genes are under direct or indirect control of sigmaS and that sigmaS should be considered a second vegetative sigma factor with a major impact not only on stress tolerance but on the entire cell physiology under nonoptimal growth conditions. This large data set allowed us to unequivocally identify a sigmaS consensus promoter in silico. Moreover, our results suggest that sigmaS-dependent genes represent a regulatory network with complex internal control (as exemplified by the acid resistance genes). This network also exhibits extensive regulatory overlaps with other global regulons (e.g., the cyclic AMP receptor protein regulon). In addition, the global regulatory protein Lrp was found to affect sigmaS and/or sigma70 selectivity of many promoters. These observations indicate that certain modules of the sigmaS-dependent general stress response can be temporarily recruited by stress-specific regulons, which are controlled by other stress-responsive regulators that act together with sigma70 RNA polymerase. Thus, not only the expression of genes within a regulatory network but also the architecture of the network itself can be subject to regulation. PMID:15716429

  9. The sigma factor sigma s affects antibiotic production and biological control activity of Pseudomonas fluorescens Pf-5.

    PubMed

    Sarniguet, A; Kraus, J; Henkels, M D; Muehlchen, A M; Loper, J E

    1995-12-19

    Pseudomonas fluorescens Pf-5, a rhizosphere-inhabiting bacterium that suppresses several soilborne pathogens of plants, produces the antibiotics pyrrolnitrin, pyoluteorin, and 2,4-diacetylphloroglucinol. A gene necessary for pyrrolnitrin production by Pf-5 was identified as rpoS, which encodes the stationary-phase sigma factor sigma s. Several pleiotropic effects of an rpoS mutation in Escherichia coli also were observed in an RpoS- mutant of Pf-5. These included sensitivities of stationary-phase cells to stresses imposed by hydrogen peroxide or high salt concentration. A plasmid containing the cloned wild-type rpoS gene restored pyrrolnitrin production and stress tolerance to the RpoS- mutant of Pf-5. The RpoS- mutant overproduced pyoluteorin and 2,4-diacetyl-phloroglucinol, two antibiotics that inhibit growth of the phytopathogenic fungus Pythium ultimum, and was superior to the wild type in suppression of seedling damping-off of cucumber caused by Pythium ultimum. When inoculated onto cucumber seed at high cell densities, the RpoS- mutant did not survive as well as the wild-type strain on surfaces of developing seedlings. Other stationary-phase-specific phenotypes of Pf-5, such as the production of cyanide and extracellular protease(s) were expressed by the RpoS- mutant, suggesting that sigma s is only one of the sigma factors required for the transcription of genes in stationary-phase cells of P. fluorescens. These results indicate that a sigma factor encoded by rpoS influences antibiotic production, biological control activity, and survival of P. fluorescens on plant surfaces. PMID:8618880

  10. Structures of FolT in substrate-bound and substrate-released conformations reveal a gating mechanism for ECF transporters

    NASA Astrophysics Data System (ADS)

    Zhao, Qin; Wang, Chengcheng; Wang, Chengyuan; Guo, Hui; Bao, Zhihao; Zhang, Minhua; Zhang, Peng

    2015-07-01

    Energy-coupling factor (ECF) transporters are a new family of ABC transporters that consist of four subunits, two cytoplasmic ATPases EcfA and EcfA' and two transmembrane proteins namely EcfS for substrate-specific binding and EcfT for energy coupling. Here, we report the 3.2-Å resolution crystal structure of the EcfS protein of a folate ECF transporter from Enterococcus faecalis-EfFolT, a close homologue of FolT from Lactobacillus brevis-LbFolT. Structural and biochemical analyses reveal the residues constituting the folate-binding pocket and determining the substrate-binding specificity. Structural comparison of the folate-bound EfFolT with the folate-free LbFolT contained in the holotransporter complex discloses significant conformational change at the L1 loop, and reveals a gating mechanism of ECF transporters in which the L1 loop of EcfS acts as a gate in the substrate binding and release.

  11. Structures of FolT in substrate-bound and substrate-released conformations reveal a gating mechanism for ECF transporters

    PubMed Central

    Zhao, Qin; Wang, Chengcheng; Wang, Chengyuan; Guo, Hui; Bao, Zhihao; Zhang, Minhua; Zhang, Peng

    2015-01-01

    Energy-coupling factor (ECF) transporters are a new family of ABC transporters that consist of four subunits, two cytoplasmic ATPases EcfA and EcfA' and two transmembrane proteins namely EcfS for substrate-specific binding and EcfT for energy coupling. Here, we report the 3.2-Å resolution crystal structure of the EcfS protein of a folate ECF transporter from Enterococcus faecalis-EfFolT, a close homologue of FolT from Lactobacillus brevis-LbFolT. Structural and biochemical analyses reveal the residues constituting the folate-binding pocket and determining the substrate-binding specificity. Structural comparison of the folate-bound EfFolT with the folate-free LbFolT contained in the holotransporter complex discloses significant conformational change at the L1 loop, and reveals a gating mechanism of ECF transporters in which the L1 loop of EcfS acts as a gate in the substrate binding and release. PMID:26198469

  12. The Clostridium difficile Dlt Pathway Is Controlled by the Extracytoplasmic Function Sigma Factor σV in Response to Lysozyme.

    PubMed

    Woods, Emily C; Nawrocki, Kathryn L; Suárez, Jose M; McBride, Shonna M

    2016-06-01

    Clostridium difficile (also known as Peptoclostridium difficile) is a major nosocomial pathogen and a leading cause of antibiotic-associated diarrhea throughout the world. Colonization of the intestinal tract is necessary for C. difficile to cause disease. Host-produced antimicrobial proteins (AMPs), such as lysozyme, are present in the intestinal tract and can deter colonization by many bacterial pathogens, and yet C. difficile is able to survive in the colon in the presence of these AMPs. Our prior studies established that the Dlt pathway, which increases the surface charge of the bacterium by addition of d-alanine to teichoic acids, is important for C. difficile resistance to a variety of AMPs. We sought to determine what genetic mechanisms regulate expression of the Dlt pathway. In this study, we show that a dlt null mutant is severely attenuated for growth in lysozyme and that expression of the dltDABC operon is induced in response to lysozyme. Moreover, we found that a mutant lacking the extracytoplasmic function (ECF) sigma factor σ(V) does not induce dlt expression in response to lysozyme, indicating that σ(V) is required for regulation of lysozyme-dependent d-alanylation of the cell wall. Using reporter gene fusions and 5' RACE (rapid amplification of cDNA ends) analysis, we identified promoter elements necessary for lysozyme-dependent and lysozyme-independent dlt expression. In addition, we observed that both a sigV mutant and a dlt mutant are more virulent in a hamster model of infection. These findings demonstrate that cell wall d-alanylation in C. difficile is induced by lysozyme in a σ(V)-dependent manner and that this pathway impacts virulence in vivo. PMID:27068095

  13. An extracytoplasmic function sigma factor-dependent periplasmic glutathione peroxidase is involved in oxidative stress response of Shewanella oneidensis

    DOE PAGESBeta

    Dai, Jingcheng; Wei, Hehong; Tian, Chunyuan; Damron, Fredrick; Zhou, Jizhong; Qiu, Dongru

    2015-01-01

    Background: Bacteria use alternative sigma factors (σs) to regulate condition-specific gene expression for survival and Shewanella harbors multiple ECF (extracytoplasmic function) σ genes and cognate anti-sigma factor genes. Here we comparatively analyzed two of the rpoE-like operons in the strain MR-1: rpoE-rseA-rseB-rseC and rpoE2-chrR. Results: RpoE was important for bacterial growth at low and high temperatures, in the minimal medium, and high salinity. The degP/htrA orthologue, required for growth of Escherichia coli and Pseudomonas aeruginosa at high temperature, is absent in Shewanella, while the degQ gene is RpoE-regulated and is required for bacterial growth at high temperature. RpoE2 was essentialmore » for the optimal growth in oxidative stress conditions because the rpoE2 mutant was sensitive to hydrogen peroxide and paraquat. The operon encoding a ferrochelatase paralogue (HemH2) and a periplasmic glutathione peroxidase (PgpD) was identified as RpoE2-dependent. PgpD exhibited higher activities and played a more important role in the oxidative stress responses than the cytoplasmic glutathione peroxidase CgpD under tested conditions. The rpoE2-chrR operon and the identified regulon genes, including pgpD and hemH2, are coincidently absent in several psychrophilic and/or deep-sea Shewanella strains. Conclusion: In S. oneidensis MR-1, the RpoE-dependent degQ gene is required for optimal growth under high temperature. The rpoE2 and RpoE2-dependent pgpD gene encoding a periplasmic glutathione peroxidase are involved in oxidative stress responses. But rpoE2 is not required for bacterial growth at low temperature and it even affected bacterial growth under salt stress, indicating that there is a tradeoff between the salt resistance and RpoE2-mediated oxidative stress responses.« less

  14. An extracytoplasmic function sigma factor-dependent periplasmic glutathione peroxidase is involved in oxidative stress response of Shewanella oneidensis

    SciTech Connect

    Dai, Jingcheng; Wei, Hehong; Tian, Chunyuan; Damron, Fredrick; Zhou, Jizhong; Qiu, Dongru

    2015-01-01

    Background: Bacteria use alternative sigma factors (σs) to regulate condition-specific gene expression for survival and Shewanella harbors multiple ECF (extracytoplasmic function) σ genes and cognate anti-sigma factor genes. Here we comparatively analyzed two of the rpoE-like operons in the strain MR-1: rpoE-rseA-rseB-rseC and rpoE2-chrR. Results: RpoE was important for bacterial growth at low and high temperatures, in the minimal medium, and high salinity. The degP/htrA orthologue, required for growth of Escherichia coli and Pseudomonas aeruginosa at high temperature, is absent in Shewanella, while the degQ gene is RpoE-regulated and is required for bacterial growth at high temperature. RpoE2 was essential for the optimal growth in oxidative stress conditions because the rpoE2 mutant was sensitive to hydrogen peroxide and paraquat. The operon encoding a ferrochelatase paralogue (HemH2) and a periplasmic glutathione peroxidase (PgpD) was identified as RpoE2-dependent. PgpD exhibited higher activities and played a more important role in the oxidative stress responses than the cytoplasmic glutathione peroxidase CgpD under tested conditions. The rpoE2-chrR operon and the identified regulon genes, including pgpD and hemH2, are coincidently absent in several psychrophilic and/or deep-sea Shewanella strains. Conclusion: In S. oneidensis MR-1, the RpoE-dependent degQ gene is required for optimal growth under high temperature. The rpoE2 and RpoE2-dependent pgpD gene encoding a periplasmic glutathione peroxidase are involved in oxidative stress responses. But rpoE2 is not required for bacterial growth at low temperature and it even affected bacterial growth under salt stress, indicating that there is a tradeoff between the salt resistance and RpoE2-mediated oxidative stress responses.

  15. Characterization of the Promoter Motif Regulated by PSPTO_1209 a FecI-like ECF Sigma Factor of Pseudomonas syringae pv. tomato DC3000

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pseudomanads are renowned for their capacity to adapt to diverse environments, a fact that is reflected in the fraction of their genomes dedicated to encoding transcription regulators. Members of the Pseudomonas genus include species that are adapted to pathogenic and symbiotic lifestyles in associ...

  16. An ECF sigma factor mediated cell surface signaling system in Pseudomonas syringae pv. tomato DC3000 regulates gene expression in response to heterologous siderophores

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The diversity of regulatory systems encoded by bacteria provides an indication of the variety of stresses and interactions that these organisms encounter in nature. We have been investigating how the plant pathogen, Pseudomonas syringae pv. tomato DC3000, responds to iron limitation and have focuse...

  17. Unveiling the gating mechanism of ECF Transporter RibU

    NASA Astrophysics Data System (ADS)

    Song, Jianing; Ji, Changge; Zhang, John Z. H.

    2013-12-01

    Energy-coupling factor (ECF) transporters are responsible for uptake of micronutrients in prokaryotes. The recently reported crystal structure of an ECF transporter RibU provided a foundation for understanding the structure and transport mechanism of ECF transporters. In the present study, molecular dynamics (MD) was carried out to study the conformational changes of the S component RibU upon binding by riboflavin. Our result and analysis revealed a critically important gating mechanism, in which part of loop5 (L5') (eleven residues, missing in the crystal structure) between TM5 and TM6 is dynamically flexible and serves as a gate. Specifically, the L5' opens a large cavity accessible to riboflavin from the extracellular space in Apo-RibU and closes the cavity upon riboflavin binding through hydrophobic packing with riboflavin. Thus, L5'is proposed to be the gate for riboflavin binding. In addition, steered molecular dynamics (SMD) simulation is employed to investigate the translocation dynamics of RibU during riboflavin transport. The simulation result does not show evidence that the S component alone can carry out the transport function. Since loop regions are very flexible and therefore could not be resolved by crystallography, their dynamics are hard to predict based on crystal structure alone.

  18. Growth phase-regulated expression of bolA and morphology of stationary-phase Escherichia coli cells are controlled by the novel sigma factor sigma S.

    PubMed

    Lange, R; Hengge-Aronis, R

    1991-07-01

    The novel sigma factor (sigma S) encoded by rpoS (katF) is required for induction of many growth phase-regulated genes and expression of a variety of stationary-phase phenotypes in Escherichia coli. Here we demonstrate that wild-type cells exhibit spherical morphology in stationary phase, whereas rpoS mutant cells remain rod shaped and are generally larger. Size reduction of E. coli cells along the growth curve is a continuous and at least biphasic process, the second phase of which is absent in rpoS-deficient cells and correlates with induction of the morphogene bolA in wild-type cells. Stationary-phase induction of bolA is dependent on sigma S. The "gearbox" a characteristic sequence motif present in the sigma S-dependent growth phase- and growth rate-regulated bolAp1 promoter, is not recognized by sigma S, since stationary-phase induction of the mcbA promoter, which also contains a gearbox, does not require sigma S, and other sigma S-controlled promoters do not contain gearboxes. However, good homology to the potential -35 and -10 consensus sequences for sigma S regulation is found in the bolAp1 promoter. PMID:1648559

  19. Implication from the predicted docked interaction of sigma H and exploration of its interaction with RNA polymerase in Mycobacterium tuberculosis.

    PubMed

    Gupta, Aayatti Mallick; Bhattacharya, Simanti; Bagchi, Angshuman; Mandal, Sukhendu

    2015-01-01

    M. tuberculosis is adapted to remain active in the extreme environmental condition due to the presence of atypical sigma factors commonly called extra cytoplasmic function (ECF) sigma factors. Among the 13 sigma factors of M. tuberculosis, 10 are regarded as the ECF sigma factor that exerts their attributes in various stress response. Therefore it is of interest to describe the structural prediction of one of the ECF sigma factors, sigma H (SigH), involved in oxidative and heat stress having interaction with the β׳ subunit of M. tuberculosis. RNA polymerase (Mtb-RNAP). The model of Mtb-SigH was build using the commercial package of Discovery Studio version 2.5 from Accelerys (San Diego, CA, USA) containing the inbuilt MODELER module and that of β׳ subunit of Mtb-RNAP using Phyre Server. Further, the protein models were docked using the fully automated web tool ClusPro (cluspro.bu.edu/login.php). Mtb-SigH is a triple helical structure having a putative DNA-binding site and the β׳ subunit of MtbRNAP consists of 18-beta sheets and 22 helices. The SigH-Mtb-RNAP β׳ interaction studies showed that Arg26, Gln19 andAsp18, residues of SigH protein are involved in binding with Arg137, Gln140, Arg152, Asn133 and Asp144 of β׳ subunit of Mtb-RNAP. The predicted model helps to explore the molecular mechanism in the control of gene regulation with a novel unique target for potential new generation inhibitor. PMID:26229290

  20. A novel sigma factor reveals a unique regulon controlling cell-specific recombination in Mycoplasma genitalium.

    PubMed

    Torres-Puig, Sergi; Broto, Alicia; Querol, Enrique; Piñol, Jaume; Pich, Oscar Q

    2015-05-26

    The Mycoplasma genitalium MG428 protein shows homology to members of the sigma-70 family of sigma factors. Herein, we found that MG428 activates transcription of recA, ruvA and ruvB as well as several genes with unknown function. Deletion of MG_428 or some of the up-regulated unknown genes led to severe recombination defects. Single cell analyses revealed that activation of the MG428-regulon is a rare event under laboratory growth conditions. A conserved sequence with sigma-70 promoter architecture (TTGTCA-N(18/19)-ATTWAT) was identified in the upstream region of all of the MG428-regulated genes or operons. Primer extension analyses demonstrated that transcription initiates immediately downstream of this sigma70-type promoter in a MG428-dependent manner. Furthermore, mutagenesis of the conserved -10 and -35 elements corroborated the requirement of these regions for promoter function. Therefore, a new mycoplasma promoter directs transcription of a unique recombination regulon. Additionally, MG428 was found to interact with the RNAP core enzyme, reinforcing the predicted role of this protein as an alternative sigma factor. Finally, our results indicate that MG428 contributes to the generation of genetic diversity in this model organism. Since recombination is an important mechanism to generate antigenic variation, MG428 emerges as a novel factor contributing to M. genitalium virulence. PMID:25925568

  1. A novel sigma factor reveals a unique regulon controlling cell-specific recombination in Mycoplasma genitalium

    PubMed Central

    Torres-Puig, Sergi; Broto, Alicia; Querol, Enrique; Piñol, Jaume; Pich, Oscar Q.

    2015-01-01

    The Mycoplasma genitalium MG428 protein shows homology to members of the sigma-70 family of sigma factors. Herein, we found that MG428 activates transcription of recA, ruvA and ruvB as well as several genes with unknown function. Deletion of MG_428 or some of the up-regulated unknown genes led to severe recombination defects. Single cell analyses revealed that activation of the MG428-regulon is a rare event under laboratory growth conditions. A conserved sequence with sigma-70 promoter architecture (TTGTCA-N18/19-ATTWAT) was identified in the upstream region of all of the MG428-regulated genes or operons. Primer extension analyses demonstrated that transcription initiates immediately downstream of this sigma70-type promoter in a MG428-dependent manner. Furthermore, mutagenesis of the conserved −10 and −35 elements corroborated the requirement of these regions for promoter function. Therefore, a new mycoplasma promoter directs transcription of a unique recombination regulon. Additionally, MG428 was found to interact with the RNAP core enzyme, reinforcing the predicted role of this protein as an alternative sigma factor. Finally, our results indicate that MG428 contributes to the generation of genetic diversity in this model organism. Since recombination is an important mechanism to generate antigenic variation, MG428 emerges as a novel factor contributing to M. genitalium virulence. PMID:25925568

  2. Planar substrate-binding site dictates the specificity of ECF-type nickel/cobalt transporters

    PubMed Central

    Yu, You; Zhou, Mingze; Kirsch, Franziska; Xu, Congqiao; Zhang, Li; Wang, Yu; Jiang, Zheng; Wang, Na; Li, Jun; Eitinger, Thomas; Yang, Maojun

    2014-01-01

    The energy-coupling factor (ECF) transporters are multi-subunit protein complexes that mediate uptake of transition-metal ions and vitamins in about 50% of the prokaryotes, including bacteria and archaea. Biological and structural studies have been focused on ECF transporters for vitamins, but the molecular mechanism by which ECF systems transport metal ions from the environment remains unknown. Here we report the first crystal structure of a NikM, TtNikM2, the substrate-binding component (S component) of an ECF-type nickel transporter from Thermoanaerobacter tengcongensis. In contrast to the structures of the vitamin-specific S proteins with six transmembrane segments (TSs), TtNikM2 possesses an additional TS at its N-terminal region, resulting in an extracellular N-terminus. The highly conserved N-terminal loop inserts into the center of TtNikM2 and occludes a region corresponding to the substrate-binding sites of the vitamin-specific S components. Nickel binds to NikM via its coordination to four nitrogen atoms, which are derived from Met1, His2 and His67 residues. These nitrogen atoms form an approximately square-planar geometry, similar to that of the metal ion-binding sites in the amino-terminal Cu2+- and Ni2+-binding (ATCUN) motif. Replacements of residues in NikM contributing to nickel coordination compromised the Ni-transport activity. Furthermore, systematic quantum chemical investigation indicated that this geometry enables NikM to also selectively recognize Co2+. Indeed, the structure of TtNikM2 containing a bound Co2+ ion has almost no conformational change compared to the structure that contains a nickel ion. Together, our data reveal an evolutionarily conserved mechanism underlying the metal selectivity of EcfS proteins, and provide insights into the ion-translocation process mediated by ECF transporters. PMID:24366337

  3. Molecular cloning and characterization of two genes encoding sigma factors that direct transcription from a Bacillus thuringiensis crystal protein gene promoter.

    PubMed Central

    Adams, L F; Brown, K L; Whiteley, H R

    1991-01-01

    Two sigma factors, sigma 35 and sigma 28, direct transcription from the Bt I and Bt II promoters of the cryIA(a) gene of Bacillus thuringiensis; this gene encodes a lepidopteran-specific crystal protoxin. These sigma factors were biochemically characterized in previous work (K. L. Brown and H. R. Whiteley, Proc. Natl. Acad. Sci. USA 85:4166-4170, 1988; K. L. Brown and H. R. Whiteley, J. Bacteriol. 172:6682-6688, 1990). In this paper, we describe the cloning of the genes encoding these two sigma factors, as well as their nucleotide and deduced amino acid sequences. The deduced amino acid sequences of the sigma 35 and sigma 28 genes show 88 and 85% identity, respectively, to the sporulation-specific sigma E and sigma K polypeptides of Bacillus subtilis. Transformation of the sigma 35 and sigma 28 genes into B. subtilis shows that the respective B. thuringiensis sigma factor genes can complement spoIIG55 (sigma E) and spoIIIC94 (sigma K) defects. Further, B. thuringiensis core polymerase reconstituted with either the sigma 35 or sigma 28 polypeptide directs transcription from B. subtilis promoters recognized by B. subtilis RNA polymerase containing sigma E and sigma K, respectively. Thus, sigma 35 and sigma 28 of B. thuringiensis appear to be functionally equivalent to sigma E and sigma K of B. subtilis. However, unlike the situation for sigma K in B. subtilis, the homologous sigma 28 gene in B. thuringiensis does not result from a late-sporulation-phase chromosomal rearrangement of two separate, partial genes. Images PMID:1904859

  4. Structure and Mechanism of the S Component of a Bacterial ECF Transporter

    SciTech Connect

    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.

  5. Brain ECF antioxidant interactions in hamsters during arousal from hibernation.

    PubMed

    Osborne, Peter G; Hashimoto, Masaaki

    2007-03-12

    Warming from hibernation to cenothermia involves intense metabolic activity and large fluxes in regional blood flow and volume. During this transition, levels of the antioxidants, ascorbate (AA), urate and glutathione (GSH) in brain tissue, extracellular fluid (ECF) and plasma change substantially. Striatal ECF was sampled and manipulated using very slow perfusion microdialysis to examine the mechanisms that influence the changing profile of striatal ECF AA, urate and GSH levels during arousal from hibernation to cenothermia in Syrian hamsters (Mesocricetus auratus). Omission of glucose from the perfusate had no effect upon the respective decrease, increase and transient increase in striatal ECF levels of AA, GSH and urate observed during arousal from hibernation to cenothermia. In contrast, inhibition of xanthine dehydrogenase/oxidase (XOR) activity by reverse dialysis with oxypurinol, itself a free radical scavenger, decreased ECF urate and preserved ECF AA levels. This suggests that some ECF AA is oxidized by free radical products of XOR flux and/or by other free radical producing processes activated during the transition from hibernation to cenothermia. Local supplementation of ECF AA, GSH and cystiene had no effect upon the profile of transient increase of ECF urate observed during arousal from hibernation. The production of free radicals by XOR and the disappearance of AA from the ECF continues for at least 2h immediately after the hamster has attained cenothermia. The hamster, immediately after arousal from hibernation, can be utilized as a natural model to study free radical production and effective scavenging at cenothermia. PMID:17207864

  6. RNA Polymerase Sigma Factor That Blocks Morphological Differentiation by Streptomyces coelicolor

    PubMed Central

    Gehring, Amy M.; Yoo, Narie J.; Losick, Richard

    2001-01-01

    The filamentous bacterium Streptomyces coelicolor undergoes a complicated process of morphological differentiation that begins with the formation of an aerial mycelium and culminates in sporulation. Genes required for the initiation of aerial mycelium formation have been termed bld (bald), describing the smooth, undifferentiated colonies of mutant strains. By using an insertional mutagenesis protocol that relies on in vitro transposition, we have isolated a bld mutant harboring an insertion in a previously uncharacterized gene, SCE59.12c, renamed here rsuA. The insertion mutant exhibited no measurable growth defect but failed to produce an aerial mycelium and showed a significant delay in the production of the polyketide antibiotic actinorhodin. The rsuA gene encodes an apparent anti-sigma factor and is located immediately downstream of SCE59.13c, renamed here sigU, whose product is inferred to be a member of the extracytoplasmic function subfamily of RNA polymerase sigma factors. The absence of rsuA in a strain that contained sigU caused a block in development, and the overexpression of sigU in an otherwise wild-type strain caused a delay in aerial mycelium formation. However, a strain in which both rsuA and sigU had been deleted was able to undergo morphological differentiation normally. We conclude that the rsuA-encoded anti-sigma factor is responsible for antagonizing the function of the sigma factor encoded by sigU. We also conclude that the sigU-encoded sigma factor is not normally required for development but that its uncontrolled activity obstructs morphological differentiation at an early stage. PMID:11566999

  7. M. tuberculosis intramembrane protease Rip1 controls transcription through three anti-sigma factor substrates.

    PubMed

    Sklar, Joseph G; Makinoshima, Hideki; Schneider, Jessica S; Glickman, Michael S

    2010-08-01

    Regulated intramembrane proteolysis (RIP) is a mechanism of transmembrane signal transduction that functions through intramembrane proteolysis of substrates. We previously reported that the RIP metalloprotease Rv2869c (Rip1) is a determinant of Mycobacterium tuberculosis (Mtb) cell envelope composition and virulence, but the substrates of Rip1 were undefined. Here we show that Rip1 cleaves three transmembrane anti-sigma factors: anti-SigK, anti-SigL and anti-SigM, negative regulators of Sigma K, L and M. We show that transcriptional activation of katG in response to phenanthroline requires activation of SigK and SigL by Rip1 cleavage of anti-SigK and anti-SigL. We also demonstrate a Rip1-dependent pathway that activates the genes for the mycolic acid biosynthetic enzyme KasA and the resuscitation promoting factor RpfC, but represses the bacterioferritin encoding gene bfrB. Regulation of these three genes by Rip1 is not reproduced by deletion of Sigma K, L or M, either indicating a requirement for multiple Rip1 substrates or additional arms of the Rip1 pathway. These results identify a branched proteolytic signal transduction system in which a single intramembrane protease cleaves three anti-sigma factor substrates to control multiple downstream pathways involved in lipid biosynthesis and defence against oxidative stress. PMID:20545848

  8. Bacterial Sigma Factors as Targets for Engineered or Synthetic Transcriptional Control

    PubMed Central

    Tripathi, Lakshmi; Zhang, Yan; Lin, Zhanglin

    2014-01-01

    Sigma (σ) factors are the predominant constituents of transcription regulation in bacteria. σ Factors recruit the core RNA polymerase to recognize promoters with specific DNA sequences. Recently, engineering of transcriptional regulators has become a significant tool for strain engineering. The present review summarizes the recent advances in σ factor based engineering or synthetic design. The manipulation of σ factors presents insights into the bacterial stress tolerance and metabolite productivity. We envision more synthetic design based on σ factors that can be used to tune the regulatory network of bacteria. PMID:25232540

  9. Homologous pairs of regulatory proteins control activity of Bacillus subtilis transcription factor sigma(b) in response to environmental stress.

    PubMed Central

    Kang, C M; Brody, M S; Akbar, S; Yang, X; Price, C W

    1996-01-01

    In Bacillus subtilis, activity of the general stress transcription factor sigma B is controlled posttranslationally by a regulatory network that transmits signals of environmental and metabolic stress. These signals include heat, ethanol, or osmotic challenge, or a sharp decrease in cellular energy levels, and all ultimately control sigma B activity by influencing the binding decision of the RsbW anti-sigma factor. In the absence of stress, RsbW binds to sigma B and prevents its association with RNA polymerase core enzyme. However, following stress, RsbW binds instead to the RsbV anti-anti-sigma factor, thereby releasing sigma B to direct transcription of its target genes. These two principal regulators of sigmaB activity are encoded in the eight-gene sigB operon, which has the gene order rsbR-rsbS-rsbT-rsbU-rsbV-rsbW-sig B-rsbX (where rsb stands for regulator of sigma B). Notably, the predicted rsbS product has significant amino acid identity to the RsbV anti-anti-sigma factor and the predicted rsbT product resembles the RsbW anti-sigma factor. To determine the roles of rsbS and rsbT, null or missense mutations were constructed in the chromosomal copies or each and tested for their effects on expression of a sigma B-dependent reporter fusion. On the basis of this genetic analysis, our principal conclusions are that (i) the rsbS product is a negative regulator of or" activity, (ii) the rsbT product is a positive regulator, (iii) RsbS requires RsbT for function, and (iv) the RsbS-RsbT and RsbV-RsbW pairs act hierarchically by a common mechanism in which key protein-protein interactions are controlled by phosphorylation events. PMID:8682789

  10. Loss of sigma factor RpoN increases intestinal colonization of vibrio parahaemolyticus in an adult mouse model"

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vibrio parahaemolyticus is the leading cause of bacterial seafood-borne gastroenteritis worldwide, yet little is known about how this pathogen colonizes the human intestine. The alternative sigma factor RpoN/sigma-54 is a global regulator that controls flagella synthesis as well as a wide range of ...

  11. Expression of heterologous sigma factors enables functional screening of metagenomic and heterologous genomic libraries

    PubMed Central

    Gaida, Stefan M.; Sandoval, Nicholas R.; Nicolaou, Sergios A.; Chen, Yili; Venkataramanan, Keerthi P.; Papoutsakis, Eleftherios T.

    2015-01-01

    A key limitation in using heterologous genomic or metagenomic libraries in functional genomics and genome engineering is the low expression of heterologous genes in screening hosts, such as Escherichia coli. To overcome this limitation, here we generate E. coli strains capable of recognizing heterologous promoters by expressing heterologous sigma factors. Among seven sigma factors tested, RpoD from Lactobacillus plantarum (Lpl) appears to be able of initiating transcription from all sources of DNA. Using the promoter GFP-trap concept, we successfully screen several heterologous and metagenomic DNA libraries, thus enlarging the genomic space that can be functionally sampled in E. coli. For an application, we show that screening fosmid-based Lpl genomic libraries in an E. coli strain with a chromosomally integrated Lpl rpoD enables the identification of Lpl genetic determinants imparting strong ethanol tolerance in E. coli. Transcriptome analysis confirms increased expression of heterologous genes in the engineered strain. PMID:25944046

  12. Use of In Vitro Transcription System for Analysis of Corynebacterium glutamicum Promoters Recognized by Two Sigma Factors.

    PubMed

    Šilar, Radoslav; Holátko, Jiří; Rucká, Lenka; Rapoport, Andrey; Dostálová, Hana; Kadeřábková, Pavla; Nešvera, Jan; Pátek, Miroslav

    2016-09-01

    Promoter activities in Corynebacterium glutamicum strains with deletions of genes encoding sigma factors of RNA polymerase suggested that transcription from some promoters is controlled by two sigma factors. To prove that different sigma factors are involved in the recognition of selected Corynebacterium glutamicum promoters, in vitro transcription system was applied. It was found that a typical housekeeping promoter Pper interacts with the alternative sigma factor σ(B) in addition to the primary sigma factor σ(A). On the other way round, the σ(B)-dependent promoter of the pqo gene that is expressed mainly in the stationary growth phase was active also with σ(A). Some promoters of genes involved in stress responses (P1clgR, P2dnaK, and P2dnaJ2) were found to be recognized by two stress-responding sigma factors, σ(H) and σ(E). In vitro transcription system thus proved to be a useful direct technique for demonstrating the overlap of different sigma factors in recognition of individual promoters in C. glutamicum. PMID:27270733

  13. Roles of SigB and SigF in the Mycobacterium tuberculosis sigma factor network.

    PubMed

    Lee, Jong-Hee; Karakousis, Petros C; Bishai, William R

    2008-01-01

    To characterize the roles of SigB and SigF in sigma factor regulation in Mycobacterium tuberculosis, we used chemically inducible recombinant strains to conditionally overexpress sigB and sigF. Using whole genomic microarray analysis and quantitative reverse transcription-PCR, we investigated the resulting global transcriptional changes after sigB induction, and we specifically tested the relative expression of other sigma factor genes after knock-in expression of sigB and sigF. Overexpression of sigB resulted in significant upregulation of genes encoding several early culture filtrate antigens (ESAT-6-like proteins), ribosomal proteins, PE-PGRS proteins, the keto-acyl synthase, KasA, and the regulatory proteins WhiB2 and IdeR. Of note, the induction of sigB did not alter the expression of other sigma factor genes, indicating that SigB is likely to serve as an end regulator for at least one branch of the M. tuberculosis sigma factor regulatory cascade. Analysis of the 5'-untranslated region (UTR) of SigB-dependent transcripts revealed a putative consensus sequence of NGTGG-N(14-18)-NNGNNG. This sequence appeared upstream of both sigB (Rv2710) and the gene following it, ideR (Rv2711), and in vitro transcription analysis with recombinant SigB-reconstituted RNA polymerase confirmed SigB-dependent transcription from each of these promoters. Knock-in expression of sigF revealed that only the sigC gene was significantly upregulated 6 and 12 h after sigF induction. The previously identified SigF promoter consensus sequence AGTTTG-N(15)-GGGTTT was identified in the 5' UTR of the sigC gene, and SigF-dependent in vitro transcription of the promoter upstream of sigC was confirmed by using recombinant SigF-reconstituted RNA polymerase. These two knock-in recombinant strains were tested in a macrophage model of infection which showed that overexpression of sigB and sigF resulted in reduced rates of M. tuberculosis intracellular growth. These results define the SigB promoter

  14. Inference of sigma factor controlled networks by using numerical modeling applied to microarray time series data of the germinating prokaryote

    PubMed Central

    Strakova, Eva; Zikova, Alice; Vohradsky, Jiri

    2014-01-01

    A computational model of gene expression was applied to a novel test set of microarray time series measurements to reveal regulatory interactions between transcriptional regulators represented by 45 sigma factors and the genes expressed during germination of a prokaryote Streptomyces coelicolor. Using microarrays, the first 5.5 h of the process was recorded in 13 time points, which provided a database of gene expression time series on genome-wide scale. The computational modeling of the kinetic relations between the sigma factors, individual genes and genes clustered according to the similarity of their expression kinetics identified kinetically plausible sigma factor-controlled networks. Using genome sequence annotations, functional groups of genes that were predominantly controlled by specific sigma factors were identified. Using external binding data complementing the modeling approach, specific genes involved in the control of the studied process were identified and their function suggested. PMID:24157841

  15. Sigma factor RpoN (σ54) regulates pilE transcription in commensal Neisseria elongata.

    PubMed

    Rendón, María A; Hockenberry, Alyson M; McManus, Steven A; So, Magdalene

    2013-10-01

    Human-adapted Neisseria includes two pathogens, Neisseria gonorrhoeae and Neisseria meningitidis, and at least 13 species of commensals that colonize many of the same niches as the pathogens. The Type IV pilus plays an important role in the biology of pathogenic Neisseria. In these species, Sigma factor RpoD (σ(70)), Integration Host Factor, and repressors RegF and CrgA regulate transcription of pilE, the gene encoding the pilus structural subunit. The Type IV pilus is also a strictly conserved trait in commensal Neisseria. We present evidence that a different mechanism regulates pilE transcription in commensals. Using Neisseria elongata as a model, we show that Sigma factor RpoN (σ(54)), Integration Host Factor, and an activator we name Npa regulate pilE transcription. Taken in context with previous reports, our findings indicate pilE regulation switched from an RpoN- to an RpoD-dependent mechanism as pathogenic Neisseria diverged from commensals during evolution. Our findings have implications for the timing of Tfp expression and Tfp-mediated host cell interactions in these two groups of bacteria. PMID:23899162

  16. Identification of inhibitors of a bacterial sigma factor using a new high-throughput screening assay.

    PubMed

    El-Mowafi, S A; Sineva, E; Alumasa, J N; Nicoloff, H; Tomsho, J W; Ades, S E; Keiler, K C

    2015-01-01

    Gram-negative bacteria are formidable pathogens because their cell envelope presents an adaptable barrier to environmental and host-mediated challenges. The stress response pathway controlled by the alternative sigma factor σ(E) is critical for maintenance of the cell envelope. Because σ(E) is required for the virulence or viability of several Gram-negative pathogens, it might be a useful target for antibiotic development. To determine if small molecules can inhibit the σ(E) pathway, and to permit high-throughput screening for antibiotic lead compounds, a σ(E) activity assay that is compatible with high-throughput screening was developed and validated. The screen employs a biological assay with positive readout. An Escherichia coli strain was engineered to express yellow fluorescent protein (YFP) under negative regulation by the σ(E) pathway, such that inhibitors of the pathway increase the production of YFP. To validate the screen, the reporter strain was used to identify σ(E) pathway inhibitors from a library of cyclic peptides. Biochemical characterization of one of the inhibitory cyclic peptides showed that it binds σ(E), inhibits RNA polymerase holoenzyme formation, and inhibits σ(E)-dependent transcription in vitro. These results demonstrate that alternative sigma factors can be inhibited by small molecules and enable high-throughput screening for inhibitors of the σ(E) pathway. PMID:25331704

  17. Inhibition of transcription in Staphylococcus aureus by a primary sigma factor-binding polypeptide from phage G1.

    PubMed

    Dehbi, Mohammed; Moeck, Gregory; Arhin, Francis F; Bauda, Pascale; Bergeron, Dominique; Kwan, Tony; Liu, Jing; McCarty, John; Dubow, Michael; Pelletier, Jerry

    2009-06-01

    The primary sigma factor of Staphylococcus aureus, sigma(SA), regulates the transcription of many genes, including several essential genes, in this bacterium via specific recognition of exponential growth phase promoters. In this study, we report the existence of a novel staphylococcal phage G1-derived growth inhibitory polypeptide, referred to as G1ORF67, that interacts with sigma(SA) both in vivo and in vitro and regulates its activity. Delineation of the minimal domain of sigma(SA) that is required for its interaction with G1ORF67 as amino acids 294 to 360 near the carboxy terminus suggests that the G1 phage-encoded anti-sigma factor may occlude the -35 element recognition domain of sigma(SA). As would be predicted by this hypothesis, the G1ORF67 polypeptide abolished both RNA polymerase core-dependent binding of sigma(SA) to DNA and sigma(SA)-dependent transcription in vitro. While G1ORF67 profoundly inhibits transcription when expressed in S. aureus cells in mode of action studies, our finding that G1ORF67 was unable to inhibit transcription when expressed in Escherichia coli concurs with its inability to inhibit transcription by the E. coli holoenzyme in vitro. These features demonstrate the selectivity of G1ORF67 for S. aureus RNA polymerase. We predict that G1ORF67 is one of the central polypeptides in the phage G1 strategy to appropriate host RNA polymerase and redirect it to phage reproduction. PMID:19376864

  18. Global gene expression and the role of sigma factors in Neisseria gonorrhoeae in interactions with epithelial cells.

    PubMed

    Du, Ying; Lenz, Jonathan; Arvidson, Cindy Grove

    2005-08-01

    Like many bacterial pathogens, Neisseria gonorrhoeae must adapt to environmental changes in order to successfully colonize and proliferate in a new host. Modulation of gene expression in response to environmental signals is an efficient mechanism used by bacteria to achieve this goal. Using DNA microarrays and a tissue culture model for gonococcal infection, we examined global changes in gene expression in N. gonorrhoeae in response to adherence to host cells. Among those genes induced upon adherence to human epithelial cells in culture was rpoH, which encodes a homolog of the heat shock sigma factor, sigma(32) (RpoH), as well as genes of the RpoH regulon, groEL and groES. Attempts to construct an rpoH null mutant in N. gonorrhoeae were unsuccessful, suggesting that RpoH is essential for viability of N. gonorrhoeae. The extracytoplasmic sigma factor, RpoE (sigma(E)), while known to regulate rpoH in other bacteria, was found not to be necessary for the up-regulation of rpoH in gonococci upon adherence to host cells. To examine the role of RpoH in host cell interactions, an N. gonorrhoeae strain conditionally expressing rpoH was constructed. The results of our experiments showed that while induction of rpoH expression is not necessary for adherence of gonococci to epithelial cells, it is important for the subsequent invasion step, as gonococci depleted for rpoH invade cells two- to threefold less efficiently than a wild-type strain. Taken together, these results indicate that sigma(32), but not sigma(E), is important for the response of gonococci in the initial steps of an infection. PMID:16040997

  19. Identifying a Core RNA Polymerase Surface Critical for Interactions with a Sigma-Like Specificity Factor

    PubMed Central

    Cliften, Paul F.; Jang, Sei-Heon; Jaehning, Judith A.

    2000-01-01

    Cyclic interactions occurring between a core RNA polymerase (RNAP) and its initiation factors are critical for transcription initiation, but little is known about subunit interaction. In this work we have identified regions of the single-subunit yeast mitochondrial RNAP (Rpo41p) important for interaction with its sigma-like specificity factor (Mtf1p). Previously we found that the whole folded structure of both polypeptides as well as specific amino acids in at least three regions of Mtf1p are required for interaction. In this work we started with an interaction-defective point mutant in Mtf1p (V135A) and used a two-hybrid selection to isolate suppressing mutations in the core polymerase. We identified suppressors in three separate regions of the RNAP which, when modeled on the structure of the closely related phage T7 RNAP, appear to lie on one surface of the protein. Additional point mutations and biochemical assays were used to confirm the importance of each region for Rpo41p-Mtf1p interactions. Remarkably, two of the three suppressors are found in regions required by T7 RNAP for DNA sequence recognition and promoter melting. Although these essential regions of the phage RNAP are poorly conserved with the mitochondrial RNAPs, they are conserved among the mitochondrial enzymes. The organellar RNAPs appear to use this surface in an alternative way for interactions with their separate sigma-like specificity factor, which, like its bacterial counterpart, provides promoter recognition and DNA melting functions to the holoenzyme. PMID:10958696

  20. Arabidopsis Sigma Factor Binding Proteins Are Activators of the WRKY33 Transcription Factor in Plant Defense[W

    PubMed Central

    Lai, Zhibing; Li, Ying; Wang, Fei; Cheng, Yuan; Fan, Baofang; Yu, Jing-Quan; Chen, Zhixiang

    2011-01-01

    Necrotrophic pathogens are important plant pathogens that cause many devastating plant diseases. Despite their impact, our understanding of the plant defense response to necrotrophic pathogens is limited. The WRKY33 transcription factor is important for plant resistance to necrotrophic pathogens; therefore, elucidation of its functions will enhance our understanding of plant immunity to necrotrophic pathogens. Here, we report the identification of two WRKY33-interacting proteins, nuclear-encoded SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2, which also interact with plastid-encoded plastid RNA polymerase SIGMA FACTOR1. Both SIB1 and SIB2 contain an N-terminal chloroplast targeting signal and a putative nuclear localization signal, suggesting that they are dual targeted. Bimolecular fluorescence complementation indicates that WRKY33 interacts with SIBs in the nucleus of plant cells. Both SIB1 and SIB2 contain a short VQ motif that is important for interaction with WRKY33. The two VQ motif–containing proteins recognize the C-terminal WRKY domain and stimulate the DNA binding activity of WRKY33. Like WRKY33, both SIB1 and SIB2 are rapidly and strongly induced by the necrotrophic pathogen Botrytis cinerea. Resistance to B. cinerea is compromised in the sib1 and sib2 mutants but enhanced in SIB1-overexpressing transgenic plants. These results suggest that dual-targeted SIB1 and SIB2 function as activators of WRKY33 in plant defense against necrotrophic pathogens. PMID:21990940

  1. AtSIG6, a plastid sigma factor from Arabidopsis, reveals functional impact of cpCK2 phosphorylation

    PubMed Central

    Schweer, Jennifer; Türkeri, Hacer; Link, Brigitte; Link, Gerhard

    2010-01-01

    Plastids contain sigma factors, i.e. gene-regulatory proteins for promoter binding and transcription initiation. Despite the physical and functional similarity shared with their prokaryotic counterparts, the plant sigma factors have distinguishing features: most notably the existence of a variable extra sequence comprising their N-terminal portions. This distinct architecture is reflected by functional differences, including phosphorylation control by organellar protein kinase(s) closely related to nucleocytosolic, rather than bacterial-type, enzymes. In particular, cpCK2, a nuclear-coded plastid-targeted casein kinase 2, has been implicated as a key component in plant sigma factor phosphorylation and transcriptional regulation (Eur. J. Biochem. 269, 2002, 3329; Planta, 219, 2004, 298). Although this notion is based mainly on biochemical evidence and in vitro systems, the recent availability of Arabidopsis sigma knock-out lines for complementation by intact and mutant sigma cDNAs has opened up new strategies for the study of transcription regulatory mechanisms in vivo. Using Arabidopsis sigma factor 6 (AtSIG6) as a paradigm, we present data suggesting that: (i) this factor is a substrate for regulatory phosphorylation by cpCK2 both in vitro and in vivo; (ii) cpCK2 phosphorylation of SIG6 occurs at multiple sites, which can widely differ in their effect on the visual and/or molecular phenotype; (iii) in vivo usage of the perhaps most critical cpCK2 site defined by Ser174 requires (pre-)phosphorylation at the n + 3 serine residue Ser177, pointing to ‘pathfinder’ kinase activity capable of generating a functional cpCK2 substrate site. PMID:20088902

  2. Bacillus subtilis 168 gene lytF encodes a gamma-D-glutamate-meso-diaminopimelate muropeptidase expressed by the alternative vegetative sigma factor, sigmaD.

    PubMed

    Margot, P; Pagni, M; Karamata, D

    1999-01-01

    A gamma-D-glutamate-meso-diaminopimelate muropeptidase was detected in the vegetative growth phase of Bacillus subtilis 168. It is encoded by the monocistronic lytF operon expressed by the alternative vegetative sigma factor, sigmaD. Sequence analysis of LytF revealed two domains, an organization common to exoproteins of B. subtilis as well as to those from other organisms. The N-terminal domain contains a fivefold-repeated motif attributed to cell wall binding, whilst the C-terminal domain is probably endowed with the catalytic activity. Overexpression of LytF allowed its purification and biochemical characterization. Inactivation of lytF led to the loss of the cell-wall-bound protein 49' (CWBP49') and of the corresponding lytic activity as revealed by renaturation gel assay. Native cell walls prepared from the multiple lytC lytD lytE lytF-deficient mutant did not exhibit any autolysis, whereas walls prepared from a strain endowed with LytF but not with the other three enzymes underwent a slight lysis. Analysis of degradation products of cell wall devoid of teichoic-acid-bound O-esterified D-alanine unambiguously confirmed that LytF cuts the gamma-D-glutamate-mesodiaminopimelate bond. PMID:10206711

  3. The alternate sigma factor RpoS protects against silver ion toxicity in Salmonella enterica serovar Typhimurium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The alternative sigma factor, RpoS controls the expression of many stress response genes, including genes involved in acid and oxidative stresses. In this study, we demonstrated metal tolerance in S. enterica serovar Typhimurium, and silver ion showed the highest toxicity among the tested metal ions...

  4. Expression of the Arabidopsis Sigma Factor SIG5 Is Photoreceptor and Photosynthesis Controlled

    PubMed Central

    Mellenthin, Marina; Ellersiek, Ulrike; Börger, Anna; Baier, Margarete

    2014-01-01

    Two collections of Arabidopsis GAL4 enhancer trap lines were screened for light-intensity dependent reporter gene activation. Line N9313 was isolated for its strong light-intensity regulation. The T-DNA element trapped distant enhancers of the SIG5 promoter, which drives expression of a sigma factor involved in regulation of chloroplast genes for photosystem II core proteins. The T-DNA insertion 715 bp upstream of the transcription initiation site splits the promoter in a distal and proximal part. Both parts are sensitive to blue and red light and depend on photosynthetic electron transport activity between photosystem II and the plastoquinone pool. The mainblue-light sensitivity is localized within a 196-bp sequence (–887 to –691 bp) in the proximal promoter region It is preferentially CRY1 and PHYB controlled. Type-I and type-II phytochromes mediate red-light sensitivity via various promoter elements spread over the proximal and distal upstream region. This work characterizes SIG5 as an anterograde control factor of chloroplast gene expression, which is controlled by chloroplast signals in a retrograde manner. PMID:27135509

  5. The key sigma factor of transition phase, SigH, controls sporulation, metabolism, and virulence factor expression in Clostridium difficile.

    PubMed

    Saujet, Laure; Monot, Marc; Dupuy, Bruno; Soutourina, Olga; Martin-Verstraete, Isabelle

    2011-07-01

    Toxin synthesis in Clostridium difficile increases as cells enter into stationary phase. We first compared the expression profiles of strain 630E during exponential growth and at the onset of stationary phase and showed that genes involved in sporulation, cellular division, and motility, as well as carbon and amino acid metabolism, were differentially expressed under these conditions. We inactivated the sigH gene, which encodes an alternative sigma factor involved in the transition to post-exponential phase in Bacillus subtilis. Then, we compared the expression profiles of strain 630E and the sigH mutant after 10 h of growth. About 60% of the genes that were differentially expressed between exponential and stationary phases, including genes involved in motility, sporulation, and metabolism, were regulated by SigH, which thus appears to be a key regulator of the transition phase in C. difficile. SigH positively controls several genes required for sporulation. Accordingly, sigH inactivation results in an asporogeneous phenotype. The spo0A and CD2492 genes, encoding the master regulator of sporulation and one of its associated kinases, and the spoIIA operon were transcribed from a SigH-dependent promoter. The expression of tcdA and tcdB, encoding the toxins, and of tcdR, encoding the sigma factor required for toxin production, increased in a sigH mutant. Finally, SigH regulates the expression of genes encoding surface-associated proteins, such as the Cwp66 adhesin, the S-layer precursor, and the flagellum components. Among the 286 genes positively regulated by SigH, about 40 transcriptional units presenting a SigH consensus in their promoter regions are good candidates for direct SigH targets. PMID:21572003

  6. Predicting strength and function for promoters of the Escherichia coli alternative sigma factor, σE

    PubMed Central

    Rhodius, Virgil A.; Mutalik, Vivek K.

    2010-01-01

    Sequenced bacterial genomes provide a wealth of information but little understanding of transcriptional regulatory circuits largely because accurate prediction of promoters is difficult. We examined two important issues for accurate promoter prediction: (1) the ability to predict promoter strength and (2) the sequence properties that distinguish between active and weak/inactive promoters. We addressed promoter prediction using natural core promoters recognized by the well-studied alternative sigma factor, Escherichia coli σE, as a representative of group 4 σs, the largest σ group. To evaluate the contribution of sequence to promoter strength and function, we used modular position weight matrix models comprised of each promoter motif and a penalty score for suboptimal motif location. We find that a combination of select modules is moderately predictive of promoter strength and that imposing minimal motif scores distinguished active from weak/inactive promoters. The combined -35/-10 score is the most important predictor of activity. Our models also identified key sequence features associated with active promoters. A conserved “AAC” motif in the -35 region is likely to be a general predictor of function for promoters recognized by group 4 σs. These results provide valuable insights into sequences that govern promoter strength, distinguish active and inactive promoters for the first time, and are applicable to both in vivo and in vitro measures of promoter strength. PMID:20133665

  7. Overlapping Alternative Sigma Factor Regulons in the Response to Singlet Oxygen in Rhodobacter sphaeroides▿ †

    PubMed Central

    Nuss, Aaron M.; Glaeser, Jens; Berghoff, Bork A.; Klug, Gabriele

    2010-01-01

    Organisms performing photosynthesis in the presence of oxygen have to cope with the formation of highly reactive singlet oxygen (1O2) and need to mount an adaptive response to photooxidative stress. Here we show that the alternative sigma factors RpoHI and RpoHII are both involved in the 1O2 response and in the heat stress response in Rhodobacter sphaeroides. We propose RpoHII to be the major player in the 1O2 response, whereas RpoHI is more important for the heat stress response. Mapping of the 5′ ends of RpoHII- and also RpoHI/RpoHII-dependent transcripts revealed clear differences in the −10 regions of the putative promoter sequences. By using bioinformatic tools, we extended the RpoHII regulon, which includes genes induced by 1O2 exposure. These genes encode proteins which are, e.g., involved in methionine sulfoxide reduction and in maintaining the quinone pool. Furthermore, we identified small RNAs which depend on RpoHI and RpoHII and are likely to contribute to the defense against photooxidative stress and heat stress. PMID:20304993

  8. Enhanced Promoter Activity by Replenishment of Sigma Factor rpoE in Klebsiella pneumoniae.

    PubMed

    Chen, Liuni; Li, Ying; Tian, Pingfang

    2016-06-01

    Plasmid-dependent overexpression of enzyme(s) aims to divert carbon flux toward a desired compound. One drawback of this strategy is compromise of growth due to massive consumption of host resources. Here we show that replenishment of sigma factor rpoE improves the growth of Klebsiella pneumoniae. The gene rpoE was expressed alone or coexpressed with Ald4 (an aldehyde dehydrogenase from Saccharomyces cerevisiae) in K. pneumoniae. We found that the Ald4 activity was higher in the strain coexpressing Ald4 and rpoE (32.3 U/mg) than that expressing Ald4 alone (29.9 U/mg). Additionally, under shake-flask conditions, the strain coexpressing Ald4 and rpoE produced 0.5 g 3-hydroxypropionic acid (3-HP) and 9.8 g 1,3-propanediol (1,3-PD) per liter in 24 h, which were 1.6- and 0.85-fold enhancement, respectively, compared to those expressing Ald4 alone. Notably, under non-optimized bioreactor conditions, the strain coexpressing Ald4 and rpoE produced 13.5 g 3-HP and 37.8 g 1,3-PD per liter with glycerol conversion ratio of 0.45 mol/mol. These results indicate that replenishment of rpoE enhanced promoter activity and stimulated glycerol consumption. PMID:27570311

  9. Global Analysis of Salmonella Alternative Sigma Factor E on Protein Translation

    PubMed Central

    Li, Jie; Nakayasu, Ernesto S.; Overall, Christopher C.; Johnson, Rudd C.; Kidwai, Afshan S.; McDermott, Jason E.; Ansong, Charles; Heffron, Fred; Cambronne, Eric D.; Adkins, Joshua N.

    2015-01-01

    The alternative sigma factor E (σE) is critical for response to extracytoplasmic stress in Salmonella. Extensive studies have been conducted on σE-regulated gene expression, particularly at the transcriptional level. Increasing evidence suggests however that σE may indirectly participate in post-transcriptional regulation. In this study, we conducted sample-matched global proteomic and transcriptomic analyses to determine the level of regulation mediated by σE in Salmonella. Samples were analyzed from wild-type and isogenic rpoE mutant Salmonella cultivated in three different conditions: nutrient-rich and conditions that mimic early and late intracellular infection. We found that 30% of the observed proteome was regulated by σE combining all three conditions. In different growth conditions, σE affected the expression of a broad spectrum of Salmonella proteins required for miscellaneous functions. Those involved in transport and binding, protein synthesis, and stress response were particularly highlighted. By comparing transcriptomic and proteomic data, we identified genes post-transcriptionally regulated by σE and found that post-transcriptional regulation was responsible for a majority of changes observed in the σE-regulated proteome. Further, comparison of transcriptomic and proteomic data from hfq mutant of Salmonella demonstrated that σE-mediated post-transcriptional regulation was partially dependent on the RNA-binding protein Hfq. PMID:25686268

  10. Improving furfural tolerance of Zymomonas mobilis by rewiring a sigma factor RpoD protein.

    PubMed

    Tan, Fu-Rong; Dai, Li-Chun; Wu, Bo; Qin, Han; Shui, Zong-Xia; Wang, Jing-Li; Zhu, Qi-Li; Hu, Qi-Chun; Ruan, Zhi-Yong; He, Ming-Xiong

    2015-06-01

    Furfural from lignocellulosic hydrolysates is the key inhibitor for bio-ethanol fermentation. In this study, we report a strategy of improving the furfural tolerance in Zymomonas mobilis on the transcriptional level by engineering its global transcription sigma factor (σ(70), RpoD) protein. Three furfural tolerance RpoD mutants (ZM4-MF1, ZM4-MF2, and ZM4-MF3) were identified from error-prone PCR libraries. The best furfural-tolerance strain ZM4-MF2 reached to the maximal cell density (OD600) about 2.0 after approximately 30 h, while control strain ZM4-rpoD reached its highest cell density of about 1.3 under the same conditions. ZM4-MF2 also consumed glucose faster and yield higher ethanol; expression levels and key Entner-Doudoroff (ED) pathway enzymatic activities were also compared to control strain under furfural stress condition. Our results suggest that global transcription machinery engineering could potentially be used to improve stress tolerance and ethanol production in Z. mobilis. PMID:25895089

  11. The putative sigma factor KatF is regulated posttranscriptionally during carbon starvation.

    PubMed

    McCann, M P; Fraley, C D; Matin, A

    1993-04-01

    Transcriptional and translational 'lacZ reporter fusions were constructed to the katF gene, which encodes a putative sigma factor centrally involved in starvation-mediated general resistance in Escherichia coli. Transcription of katF was found to increase ca. twofold after carbon starvation in minimal medium. The protein fusion containing the longest fragment of katF induced ca. eightfold under the same conditions, whereas fusions to shorter segments showed only a twofold increase in expression. The protein fusion was expressed at higher levels in a strain containing a katF::Tn10 mutation, indicating katF autoregulation. The posttranscriptional regulation of katF by starvation did not require a component of the spent minimal medium. katF was also posttranscriptionally regulated during entry into late log phase in complex medium. This induction was coincident with an increase in katE transcription, suggesting that the cellular concentration of KatF directly followed the induction of the katF protein fusion. PMID:8458856

  12. Global Analysis of Salmonella Alternative Sigma Factor E on Protein Translation

    SciTech Connect

    Li, Jie; Nakayasu, Ernesto S.; Overall, Christopher C.; Johnson, Rudd C.; Kidwai, Afshan S.; McDermott, Jason E.; Ansong, Charles; Heffron, Fred; Cambronne, Eric D.; Adkins, Joshua N.

    2015-02-16

    The alternative sigma factor E (σE) is critical for response to extracytoplasmic stress in Salmonella. Extensive studies have been conducted on σE-regulated gene expression, particularly at the transcriptional level. Increasing evidence suggests however that σE may indirectly participate in post-transcriptional regulation. Here in this study, we conducted sample-matched global proteomic and transcriptomic analyses to determine the level of regulation mediated by σE in Salmonella. We analysed samples from wild type and isogenic rpoE mutant Salmonella cultivated in three different conditions; nutrient-rich and conditions that mimic early and late intracellular infection. We found that 30% of the observed proteome was regulated by σE combining all three conditions. In different growth conditions, σE affected the expression of a broad spectrum of Salmonella proteins required for miscellaneous functions. Those involved in transport and binding, protein synthesis, and stress response were particularly highlighted. By comparing transcriptomic and proteomic data, we identified genes post-transcriptionally regulated by σE and found that post-transcriptional regulation was responsible for a majority of changes observed in the σE-regulated proteome. Further, comparison of transcriptomic and proteomic data from hfq mutant of Salmonella demonstrated that σE–mediated post-transcriptional regulation was partially dependent on the RNA-binding protein Hfq.

  13. Global Analysis of Salmonella Alternative Sigma Factor E on Protein Translation

    DOE PAGESBeta

    Li, Jie; Nakayasu, Ernesto S.; Overall, Christopher C.; Johnson, Rudd C.; Kidwai, Afshan S.; McDermott, Jason E.; Ansong, Charles; Heffron, Fred; Cambronne, Eric D.; Adkins, Joshua N.

    2015-02-16

    The alternative sigma factor E (σE) is critical for response to extracytoplasmic stress in Salmonella. Extensive studies have been conducted on σE-regulated gene expression, particularly at the transcriptional level. Increasing evidence suggests however that σE may indirectly participate in post-transcriptional regulation. Here in this study, we conducted sample-matched global proteomic and transcriptomic analyses to determine the level of regulation mediated by σE in Salmonella. We analysed samples from wild type and isogenic rpoE mutant Salmonella cultivated in three different conditions; nutrient-rich and conditions that mimic early and late intracellular infection. We found that 30% of the observed proteome was regulatedmore » by σE combining all three conditions. In different growth conditions, σE affected the expression of a broad spectrum of Salmonella proteins required for miscellaneous functions. Those involved in transport and binding, protein synthesis, and stress response were particularly highlighted. By comparing transcriptomic and proteomic data, we identified genes post-transcriptionally regulated by σE and found that post-transcriptional regulation was responsible for a majority of changes observed in the σE-regulated proteome. Further, comparison of transcriptomic and proteomic data from hfq mutant of Salmonella demonstrated that σE–mediated post-transcriptional regulation was partially dependent on the RNA-binding protein Hfq.« less

  14. Global analysis of Salmonella alternative sigma factor E on protein translation

    SciTech Connect

    Li, Jie; Nakayasu, Ernesto S.; Overall, Christopher C.; Johnson, Rudd; Kidwai, Afshan S.; McDermott, Jason E.; Ansong, Charles; Heffron, Fred; Cambronne, Eric; Adkins, Joshua N.

    2015-04-03

    The alternative sigma factor E (σE) is critical for response to extracytoplasmic stress in Salmonella. Extensive studies have been conducted on σE-regulated gene expression, particularly at the transcriptional level. Increasing evidence suggests however that σE may indirectly participate in post-transcriptional regulation. In this study, we conducted sample-matched global proteomic and transcriptomic analyses to determine the level of regulation mediated by σE in Salmonella. Samples were analyzed from wild type and isogenic rpoE mutant Salmonella cultivated in three different conditions; nutrient-rich and conditions that mimic early and late intracellular infection. We found that 30% of the observed proteome was regulated by σE combining all three conditions. In different growth conditions, σE affected the expression of a broad spectrum of Salmonella proteins required for miscellaneous functions. Those involved in transport and binding, protein synthesis, and stress response were particularly highlighted. By comparing transcriptomic and proteomic data, we identified genes post-transcriptionally regulated by σE and found that post-transcriptional regulation was responsible for a majority of changes observed in the σE-regulated proteome. Further, comparison of transcriptomic and proteomic data from hfq mutant of Salmonella demonstrated that σE–mediated post-transcriptional regulation was partially dependent on the RNA-binding protein Hfq.

  15. Human Serum-Specific Activation of Alternative Sigma Factors, the Stress Responders in Aggregatibacter actinomycetemcomitans.

    PubMed

    Tang-Siegel, Gaoyan; Bumgarner, Roger; Ruiz, Teresa; Kittichotirat, Weerayuth; Chen, Weizhen; Chen, Casey

    2016-01-01

    Aggregatibacter actinomycetemcomitans, a known pathogen causing periodontal disease and infective endocarditis, is a survivor in the periodontal pocket and blood stream; both environments contain serum as a nutrient source. To screen for unknown virulence factors associated with this microorganism, A. actinomycetemcomitans was grown in serum-based media to simulate its in vivo environment. Different strains of A. actinomycetemcomitans showed distinct growth phenotypes only in the presence of human serum, and they were grouped into high- and low-responder groups. High-responders comprised mainly serotype c strains, and showed an unusual growth phenomenon, featuring a second, rapid increase in turbidity after 9-h incubation that reached a final optical density 2- to 7-fold higher than low-responders. Upon further investigation, the second increase in turbidity was not caused by cell multiplication, but by cell death. Whole transcriptomic analysis via RNA-seq identified 35 genes that were up-regulated by human serum, but not horse serum, in high-responders but not in low-responders, including prominently an alternative sigma factor rpoE (σE). A lacZ reporter construct driven by the 132-bp rpoE promoter sequence of A. actinomycetemcomitans responded dramatically to human serum within 90 min of incubation only when the construct was carried by a high responder strain. The rpoE promoter is 100% identical among high- and low-responder strains. Proteomic investigation showed potential interactions between human serum protein, e.g. apolipoprotein A1 (ApoA1) and A. actinomycetemcomitans. The data clearly indicated a different activation process for rpoE in high- versus low-responder strains. This differential human serum-specific activation of rpoE, a putative extra-cytoplasmic stress responder and global regulator, suggests distinct in vivo adaptations among different strains of A. actinomycetemcomitans. PMID:27490177

  16. Human Serum-Specific Activation of Alternative Sigma Factors, the Stress Responders in Aggregatibacter actinomycetemcomitans

    PubMed Central

    Tang-Siegel, Gaoyan; Bumgarner, Roger; Ruiz, Teresa; Kittichotirat, Weerayuth; Chen, Weizhen; Chen, Casey

    2016-01-01

    Aggregatibacter actinomycetemcomitans, a known pathogen causing periodontal disease and infective endocarditis, is a survivor in the periodontal pocket and blood stream; both environments contain serum as a nutrient source. To screen for unknown virulence factors associated with this microorganism, A. actinomycetemcomitans was grown in serum-based media to simulate its in vivo environment. Different strains of A. actinomycetemcomitans showed distinct growth phenotypes only in the presence of human serum, and they were grouped into high- and low-responder groups. High-responders comprised mainly serotype c strains, and showed an unusual growth phenomenon, featuring a second, rapid increase in turbidity after 9-h incubation that reached a final optical density 2- to 7-fold higher than low-responders. Upon further investigation, the second increase in turbidity was not caused by cell multiplication, but by cell death. Whole transcriptomic analysis via RNA-seq identified 35 genes that were up-regulated by human serum, but not horse serum, in high-responders but not in low-responders, including prominently an alternative sigma factor rpoE (σE). A lacZ reporter construct driven by the 132-bp rpoE promoter sequence of A. actinomycetemcomitans responded dramatically to human serum within 90 min of incubation only when the construct was carried by a high responder strain. The rpoE promoter is 100% identical among high- and low-responder strains. Proteomic investigation showed potential interactions between human serum protein, e.g. apolipoprotein A1 (ApoA1) and A. actinomycetemcomitans. The data clearly indicated a different activation process for rpoE in high- versus low-responder strains. This differential human serum-specific activation of rpoE, a putative extra-cytoplasmic stress responder and global regulator, suggests distinct in vivo adaptations among different strains of A. actinomycetemcomitans. PMID:27490177

  17. Increased bioplastic production with an RNA polymerase sigma factor SigE during nitrogen starvation in Synechocystis sp. PCC 6803.

    PubMed

    Osanai, Takashi; Numata, Keiji; Oikawa, Akira; Kuwahara, Ayuko; Iijima, Hiroko; Doi, Yoshiharu; Tanaka, Kan; Saito, Kazuki; Hirai, Masami Yokota

    2013-12-01

    Because cyanobacteria directly harvest CO2 and light energy, their carbon metabolism is important for both basic and applied sciences. Here, we show that overexpression of the sigma factor sigE in Synechocystis sp. PCC 6803 widely changes sugar catabolism and increases production of the biodegradable polyester polyhydroxybutyrate (PHB) during nitrogen starvation. sigE overexpression elevates the levels of proteins implicated in glycogen catabolism, the oxidative pentose phosphate pathway, and polyhydroxyalkanoate biosynthesis. PHB accumulation is enhanced by sigE overexpression under nitrogen-limited conditions, yet the molecular weights of PHBs synthesized by the parental glucose-tolerant and sigE overexpression strain are similar. Although gene expression induced by nitrogen starvation is changed and other metabolites (such as GDP-mannose and citrate) accumulate under sigE overexpression, genetic engineering of this sigma factor altered the metabolic pathway from glycogen to PHB during nitrogen starvation. PMID:23861321

  18. Elucidation of sigma factor-associated networks in Pseudomonas aeruginosa reveals a modular architecture with limited and function-specific crosstalk.

    PubMed

    Schulz, Sebastian; Eckweiler, Denitsa; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Dötsch, Andreas; Hornischer, Klaus; Bruchmann, Sebastian; Düvel, Juliane; Häussler, Susanne

    2015-03-01

    Sigma factors are essential global regulators of transcription initiation in bacteria which confer promoter recognition specificity to the RNA polymerase core enzyme. They provide effective mechanisms for simultaneously regulating expression of large numbers of genes in response to challenging conditions, and their presence has been linked to bacterial virulence and pathogenicity. In this study, we constructed nine his-tagged sigma factor expressing and/or deletion mutant strains in the opportunistic pathogen Pseudomonas aeruginosa. To uncover the direct and indirect sigma factor regulons, we performed mRNA profiling, as well as chromatin immunoprecipitation coupled to high-throughput sequencing. We furthermore elucidated the de novo binding motif of each sigma factor, and validated the RNA- and ChIP-seq results by global motif searches in the proximity of transcriptional start sites (TSS). Our integrated approach revealed a highly modular network architecture which is composed of insulated functional sigma factor modules. Analysis of the interconnectivity of the various sigma factor networks uncovered a limited, but highly function-specific, crosstalk which orchestrates complex cellular processes. Our data indicate that the modular structure of sigma factor networks enables P. aeruginosa to function adequately in its environment and at the same time is exploited to build up higher-level functions by specific interconnections that are dominated by a participation of RpoN. PMID:25780925

  19. Elucidation of Sigma Factor-Associated Networks in Pseudomonas aeruginosa Reveals a Modular Architecture with Limited and Function-Specific Crosstalk

    PubMed Central

    Schulz, Sebastian; Eckweiler, Denitsa; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Dötsch, Andreas; Hornischer, Klaus; Bruchmann, Sebastian; Düvel, Juliane; Häussler, Susanne

    2015-01-01

    Sigma factors are essential global regulators of transcription initiation in bacteria which confer promoter recognition specificity to the RNA polymerase core enzyme. They provide effective mechanisms for simultaneously regulating expression of large numbers of genes in response to challenging conditions, and their presence has been linked to bacterial virulence and pathogenicity. In this study, we constructed nine his-tagged sigma factor expressing and/or deletion mutant strains in the opportunistic pathogen Pseudomonas aeruginosa. To uncover the direct and indirect sigma factor regulons, we performed mRNA profiling, as well as chromatin immunoprecipitation coupled to high-throughput sequencing. We furthermore elucidated the de novo binding motif of each sigma factor, and validated the RNA- and ChIP-seq results by global motif searches in the proximity of transcriptional start sites (TSS). Our integrated approach revealed a highly modular network architecture which is composed of insulated functional sigma factor modules. Analysis of the interconnectivity of the various sigma factor networks uncovered a limited, but highly function-specific, crosstalk which orchestrates complex cellular processes. Our data indicate that the modular structure of sigma factor networks enables P. aeruginosa to function adequately in its environment and at the same time is exploited to build up higher-level functions by specific interconnections that are dominated by a participation of RpoN. PMID:25780925

  20. Region 4 of Rhizobium etli Primary Sigma Factor (SigA) Confers Transcriptional Laxity in Escherichia coli.

    PubMed

    Santillán, Orlando; Ramírez-Romero, Miguel A; Lozano, Luis; Checa, Alberto; Encarnación, Sergio M; Dávila, Guillermo

    2016-01-01

    Sigma factors are RNA polymerase subunits engaged in promoter recognition and DNA strand separation during transcription initiation in bacteria. Primary sigma factors are responsible for the expression of housekeeping genes and are essential for survival. RpoD, the primary sigma factor of Escherichia coli, a γ-proteobacteria, recognizes consensus promoter sequences highly similar to those of some α-proteobacteria species. Despite this resemblance, RpoD is unable to sustain transcription from most of the α-proteobacterial promoters tested so far. In contrast, we have found that SigA, the primary sigma factor of Rhizobium etli, an α-proteobacteria, is able to transcribe E. coli promoters, although it exhibits only 48% identity (98% coverage) to RpoD. We have called this the transcriptional laxity phenomenon. Here, we show that SigA partially complements the thermo-sensitive deficiency of RpoD285 from E. coli strain UQ285 and that the SigA region σ4 is responsible for this phenotype. Sixteen out of 74 residues (21.6%) within region σ4 are variable between RpoD and SigA. Mutating these residues significantly improves SigA ability to complement E. coli UQ285. Only six of these residues fall into positions already known to interact with promoter DNA and to comprise a helix-turn-helix motif. The remaining variable positions are located on previously unexplored sites inside region σ4, specifically into the first two α-helices of the region. Neither of the variable positions confined to these helices seem to interact directly with promoter sequence; instead, we adduce that these residues participate allosterically by contributing to correct region folding and/or positioning of the HTH motif. We propose that transcriptional laxity is a mechanism for ensuring transcription in spite of naturally occurring mutations from endogenous promoters and/or horizontally transferred DNA sequences, allowing survival and fast environmental adaptation of α-proteobacteria. PMID

  1. Region 4 of Rhizobium etli Primary Sigma Factor (SigA) Confers Transcriptional Laxity in Escherichia coli

    PubMed Central

    Santillán, Orlando; Ramírez-Romero, Miguel A.; Lozano, Luis; Checa, Alberto; Encarnación, Sergio M.; Dávila, Guillermo

    2016-01-01

    Sigma factors are RNA polymerase subunits engaged in promoter recognition and DNA strand separation during transcription initiation in bacteria. Primary sigma factors are responsible for the expression of housekeeping genes and are essential for survival. RpoD, the primary sigma factor of Escherichia coli, a γ-proteobacteria, recognizes consensus promoter sequences highly similar to those of some α-proteobacteria species. Despite this resemblance, RpoD is unable to sustain transcription from most of the α-proteobacterial promoters tested so far. In contrast, we have found that SigA, the primary sigma factor of Rhizobium etli, an α-proteobacteria, is able to transcribe E. coli promoters, although it exhibits only 48% identity (98% coverage) to RpoD. We have called this the transcriptional laxity phenomenon. Here, we show that SigA partially complements the thermo-sensitive deficiency of RpoD285 from E. coli strain UQ285 and that the SigA region σ4 is responsible for this phenotype. Sixteen out of 74 residues (21.6%) within region σ4 are variable between RpoD and SigA. Mutating these residues significantly improves SigA ability to complement E. coli UQ285. Only six of these residues fall into positions already known to interact with promoter DNA and to comprise a helix-turn-helix motif. The remaining variable positions are located on previously unexplored sites inside region σ4, specifically into the first two α-helices of the region. Neither of the variable positions confined to these helices seem to interact directly with promoter sequence; instead, we adduce that these residues participate allosterically by contributing to correct region folding and/or positioning of the HTH motif. We propose that transcriptional laxity is a mechanism for ensuring transcription in spite of naturally occurring mutations from endogenous promoters and/or horizontally transferred DNA sequences, allowing survival and fast environmental adaptation of α-proteobacteria. PMID

  2. Amplification of the housekeeping sigma factor in Pseudomonas fluorescens CHA0 enhances antibiotic production and improves biocontrol abilities.

    PubMed Central

    Schnider, U; Keel, C; Blumer, C; Troxler, J; Défago, G; Haas, D

    1995-01-01

    Pseudomonas fluorescens CHA0 produces a variety of secondary metabolites, in particular the antibiotics pyoluteorin and 2,4-diacetylphloroglucinol, and protects various plants from diseases caused by soilborne pathogenic fungi. The rpoD gene encoding the housekeeping sigma factor sigma 70 of P. fluorescens was sequenced. The deduced RpoD protein showed 83% identity with RpoD of Pseudomonas aeruginosa and 67% identity with RpoD of Escherichia coli. Attempts to inactivate the single chromosomal rpoD gene of strain CHA0 were unsuccessful, indicating an essential role of this gene. When rpoD was carried by an IncP vector in strain CHA0, the production of both antibiotics was increased severalfold and, in parallel, protection of cucumber against disease caused by Pythium ultimum was improved, in comparison with strain CHA0. PMID:7665535

  3. A method for the identification of promoters recognized by RNA polymerase containing a particular sigma factor: cloning of a developmentally regulated promoter and corresponding gene directed by the Streptomyces aureofaciens sigma factor RpoZ.

    PubMed

    Nováková, R; Sevcíková, B; Kormanec, J

    1998-02-16

    We have developed a method for the identification of promoters recognized by a particular sigma factor of RNA polymerase, based on a two-compatible plasmid system in Escherichia coli (Ec). Using the method, a DNA fragment containing the promoter, PREN40, recognized by sporulation-specific Streptomyces aureofaciens (Sa) sigma factor RpoZ, was cloned. High-resolution S1 nuclease mapping using RNA prepared from Ec, and Sa from various developmental stages has shown a high degree of similarity of PREN40 to consensus sequence of flagellar and chemotaxis promoters. The promoter was induced at the time of aerial mycelium formation, and was off in the Sa strain with the rpoZ-disrupted gene. A promoter-bearing DNA fragment was inserted into the promoter-probe plasmid pARC1 to give expression patterns consistent with the results of direct RNA analysis. The region downstream of the promoter was cloned in Sa. Sequence analysis revealed an open reading frame (ORF) of 283 amino acids (Mr 30006), encoding a highly basic (pI 12.35) protein with high percentage of serine, threonine and alanine (41.8%). PMID:9479043

  4. Loss of Sigma Factor RpoN Increases Intestinal Colonization of Vibrio parahaemolyticus in an Adult Mouse Model

    PubMed Central

    Whitaker, W. Brian; Richards, Gary P.

    2014-01-01

    Vibrio parahaemolyticus is the leading cause of bacterial seafood-borne gastroenteritis worldwide, yet little is known about how this pathogen colonizes the human intestine. The alternative sigma factor RpoN/sigma-54 is a global regulator that controls flagellar synthesis, as well as a wide range of nonflagellar genes. We constructed an in-frame deletion mutation in rpoN (VP2670) in V. parahaemolyticus RIMD2210633, a clinical serogroup O3:K6 isolate, and examined the effects in vivo using a streptomycin-treated mouse model of colonization. We confirmed that deletion of rpoN rendered V. parahaemolyticus nonmotile, and it caused reduced biofilm formation and an apparent defect in glutamine synthetase production. In in vivo competition assays between the rpoN mutant and a wild-type RIMD2210633 strain marked with the β-galactosidase gene lacZ (WBWlacZ), the mutant colonized significantly more proficiently. Intestinal persistence competition assays also demonstrated that the rpoN mutant had enhanced fitness and outcompeted WBWlacZ. Mutants defective in the polar flagellum biosynthesis FliAP sigma factor also outcompeted WBWlacZ but not to the same level as the rpoN mutant, which suggested that lack of motility is not the sole cause of the fitness effect. In an in vitro growth competition assay in mouse intestinal mucus, the rpoN mutant also outcompeted the wild type and exhibited faster doubling times when grown in mucus and on individual components of mucus. Genes in the pathways for the catabolism of mucus sugars also had significantly higher expression levels in a ΔrpoN mutant than in the wild type. These data suggest that in V. parahaemolyticus, RpoN plays an important role in carbon utilization regulation, which may significantly affect host colonization. PMID:24478070

  5. Dual-specificity anti-sigma factor reinforces control of cell-type specific gene expression in Bacillus subtilis.

    PubMed

    Serrano, Mónica; Gao, JinXin; Bota, João; Bate, Ashley R; Meisner, Jeffrey; Eichenberger, Patrick; Moran, Charles P; Henriques, Adriano O

    2015-04-01

    Gene expression during spore development in Bacillus subtilis is controlled by cell type-specific RNA polymerase sigma factors. σFand σE control early stages of development in the forespore and the mother cell, respectively. When, at an intermediate stage in development, the mother cell engulfs the forespore, σF is replaced by σG and σE is replaced by σK. The anti-sigma factor CsfB is produced under the control of σF and binds to and inhibits the auto-regulatory σG, but not σF. A position in region 2.1, occupied by an asparagine in σG and by a glutamate in οF, is sufficient for CsfB discrimination of the two sigmas, and allows it to delay the early to late switch in forespore gene expression. We now show that following engulfment completion, csfB is switched on in the mother cell under the control of σK and that CsfB binds to and inhibits σE but not σK, possibly to facilitate the switch from early to late gene expression. We show that a position in region 2.3 occupied by a conserved asparagine in σE and by a conserved glutamate in σK suffices for discrimination by CsfB. We also show that CsfB prevents activation of σG in the mother cell and the premature σG-dependent activation of σK. Thus, CsfB establishes negative feedback loops that curtail the activity of σE and prevent the ectopic activation of σG in the mother cell. The capacity of CsfB to directly block σE activity may also explain how CsfB plays a role as one of the several mechanisms that prevent σE activation in the forespore. Thus the capacity of CsfB to differentiate between the highly similar σF/σG and σE/σK pairs allows it to rinforce the cell-type specificity of these sigma factors and the transition from early to late development in B. subtilis, and possibly in all sporeformers that encode a CsfB orthologue. PMID:25835496

  6. Dual-Specificity Anti-sigma Factor Reinforces Control of Cell-Type Specific Gene Expression in Bacillus subtilis

    PubMed Central

    Serrano, Mónica; Gao, JinXin; Bota, João; Bate, Ashley R.; Meisner, Jeffrey; Eichenberger, Patrick; Moran, Charles P.; Henriques, Adriano O.

    2015-01-01

    Gene expression during spore development in Bacillus subtilis is controlled by cell type-specific RNA polymerase sigma factors. σFand σE control early stages of development in the forespore and the mother cell, respectively. When, at an intermediate stage in development, the mother cell engulfs the forespore, σF is replaced by σG and σE is replaced by σK. The anti-sigma factor CsfB is produced under the control of σF and binds to and inhibits the auto-regulatory σG, but not σF. A position in region 2.1, occupied by an asparagine in σG and by a glutamate in οF, is sufficient for CsfB discrimination of the two sigmas, and allows it to delay the early to late switch in forespore gene expression. We now show that following engulfment completion, csfB is switched on in the mother cell under the control of σK and that CsfB binds to and inhibits σE but not σK, possibly to facilitate the switch from early to late gene expression. We show that a position in region 2.3 occupied by a conserved asparagine in σE and by a conserved glutamate in σK suffices for discrimination by CsfB. We also show that CsfB prevents activation of σG in the mother cell and the premature σG-dependent activation of σK. Thus, CsfB establishes negative feedback loops that curtail the activity of σE and prevent the ectopic activation of σG in the mother cell. The capacity of CsfB to directly block σE activity may also explain how CsfB plays a role as one of the several mechanisms that prevent σE activation in the forespore. Thus the capacity of CsfB to differentiate between the highly similar σF/σG and σE/σK pairs allows it to rinforce the cell-type specificity of these sigma factors and the transition from early to late development in B. subtilis, and possibly in all sporeformers that encode a CsfB orthologue. PMID:25835496

  7. Calculated hydroxyl A2 sigma --> X2 pi (0, 0) band emission rate factors applicable to atmospheric spectroscopy

    NASA Technical Reports Server (NTRS)

    Cageao, R. P.; Ha, Y. L.; Jiang, Y.; Morgan, M. F.; Yung, Y. L.; Sander, S. P.

    1997-01-01

    A calculation of the A2 sigma --> X2 pi (0, 0) band emission rate factors and line center absorption cross sections of OH applicable to its measurement using solar resonant fluorescence in the terrestrial atmosphere is presented in this paper. The most accurate available line parameters have been used. Special consideration has been given to the solar input flux because of its highly structured Fraunhofer spectrum. The calculation for the OH atmospheric emission rate factor in the solar resonant fluorescent case is described in detail with examples and intermediate results. Results of this calculation of OH emission rate factors for individual rotational lines are on average 30% lower than the values obtained in an earlier work.

  8. The anti-sigma factor RsrA responds to oxidative stress by reburying its hydrophobic core

    PubMed Central

    Rajasekar, Karthik V.; Zdanowski, Konrad; Yan, Jun; Hopper, Jonathan T. S.; Francis, Marie-Louise R.; Seepersad, Colin; Sharp, Connor; Pecqueur, Ludovic; Werner, Jörn M.; Robinson, Carol V.; Mohammed, Shabaz; Potts, Jennifer R.; Kleanthous, Colin

    2016-01-01

    Redox-regulated effector systems that counteract oxidative stress are essential for all forms of life. Here we uncover a new paradigm for sensing oxidative stress centred on the hydrophobic core of a sensor protein. RsrA is an archetypal zinc-binding anti-sigma factor that responds to disulfide stress in the cytoplasm of Actinobacteria. We show that RsrA utilizes its hydrophobic core to bind the sigma factor σR preventing its association with RNA polymerase, and that zinc plays a central role in maintaining this high-affinity complex. Oxidation of RsrA is limited by the rate of zinc release, which weakens the RsrA–σR complex by accelerating its dissociation. The subsequent trigger disulfide, formed between specific combinations of RsrA's three zinc-binding cysteines, precipitates structural collapse to a compact state where all σR-binding residues are sequestered back into its hydrophobic core, releasing σR to activate transcription of anti-oxidant genes. PMID:27432510

  9. Functional characterization of the principal sigma factor RpoD of phytoplasmas via an in vitro transcription assay

    PubMed Central

    Miura, Chihiro; Komatsu, Ken; Maejima, Kensaku; Nijo, Takamichi; Kitazawa, Yugo; Tomomitsu, Tatsuya; Yusa, Akira; Himeno, Misako; Oshima, Kenro; Namba, Shigetou

    2015-01-01

    Phytoplasmas (class, Mollicutes) are insect-transmissible and plant-pathogenic bacteria that multiply intracellularly in both plants and insects through host switching. Our previous study revealed that phytoplasmal sigma factor rpoD of OY-M strain (rpoDOY) could be a key regulator of host switching, because the expression level of rpoDOY was higher in insect hosts than in plant hosts. In this study, we developed an in vitro transcription assay system to identify RpoDOY-dependent genes and the consensus promoter elements. The assay revealed that RpoDOY regulated some housekeeping, virulence, and host–phytoplasma interaction genes of OY-M strain. The upstream region of the transcription start sites of these genes contained conserved –35 and –10 promoter sequences, which were similar to the typical bacterial RpoD-dependent promoter elements, while the –35 promoter elements were variable. In addition, we searched putative RpoD-dependent genes based on these promoter elements on the whole genome sequence of phytoplasmas using in silico tools. The phytoplasmal RpoD seems to mediate the transcription of not only many housekeeping genes as the principal sigma factor, but also the virulence- and host-phytoplasma interaction-related genes exhibiting host-specific expression patterns. These results indicate that more complex mechanisms exist than previously thought regarding gene regulation enabling phytoplasmas to switch hosts. PMID:26150080

  10. Expanding the Regulatory Network Governed by the Extracytoplasmic Function Sigma Factor σH in Corynebacterium glutamicum

    PubMed Central

    Toyoda, Koichi; Teramoto, Haruhiko; Yukawa, Hideaki

    2014-01-01

    The extracytoplasmic function sigma factor σH is responsible for the heat and oxidative stress response in Corynebacterium glutamicum. Due to the hierarchical nature of the regulatory network, previous transcriptome analyses have not been able to discriminate between direct and indirect targets of σH. Here, we determined the direct genome-wide targets of σH using chromatin immunoprecipitation with microarray technology (ChIP-chip) for analysis of a deletion mutant of rshA, encoding an anti-σ factor of σH. Seventy-five σH-dependent promoters, including 39 new ones, were identified. σH-dependent, heat-inducible transcripts for several of the new targets, including ilvD encoding a labile Fe-S cluster enzyme, dihydroxy-acid dehydratase, were detected, and their 5′ ends were mapped to the σH-dependent promoters identified. Interestingly, functional internal σH-dependent promoters were found in operon-like gene clusters involved in the pentose phosphate pathway, riboflavin biosynthesis, and Zn uptake. Accordingly, deletion of rshA resulted in hyperproduction of riboflavin and affected expression of Zn-responsive genes, possibly through intracellular Zn overload, indicating new physiological roles of σH. Furthermore, sigA encoding the primary σ factor was identified as a new target of σH. Reporter assays demonstrated that the σH-dependent promoter upstream of sigA was highly heat inducible but much weaker than the known σA-dependent one. Our ChIP-chip analysis also detected the σH-dependent promoters upstream of rshA within the sigH-rshA operon and of sigB encoding a group 2 σ factor, supporting the previous findings of their σH-dependent expression. Taken together, these results reveal an additional layer of the sigma factor regulatory network in C. glutamicum. PMID:25404703

  11. Evolution of a Sigma Factor: An All-In-One of Gene Duplication, Horizontal Gene Transfer, Purifying Selection, and Promoter Differentiation

    PubMed Central

    López-Leal, Gamaliel; Cevallos, Miguel A.; Castillo-Ramírez, Santiago

    2016-01-01

    Sigma factors are an essential part of bacterial gene regulation and have been extensively studied as far as their molecular mechanisms and protein structure are concerned. However, their molecular evolution, especially for the alternative sigma factors, is poorly understood. Here, we analyze the evolutionary forces that have shaped the rpoH sigma factors within the alphaproteobacteria. We found that an ancient duplication gave rise to two major groups of rpoH sigma factors and that after this event horizontal gene transfer (HGT) occurred in rpoH1 group. We also noted that purifying selection has differentially affected distinct parts of the gene; singularly, the gene segment that encodes the region 4.2, which interacts with the −35 motif of the RpoH-dependent genes, has been under relaxed purifying selection. Furthermore, these two major groups are clearly differentiated from one another regarding their promoter selectivity, as rpoH1 is under the transcriptional control of σ70 and σ32, whereas rpoH2 is under the transcriptional control of σ24. Our results suggest a scenario in which HGT, gene loss, variable purifying selection and clear promoter specialization occurred after the ancestral duplication event. More generally, our study offers insights into the molecular evolution of alternative sigma factors and highlights the importance of analyzing not only the coding regions but also the promoter regions. PMID:27199915

  12. The ST-ECF ACS Grism Hubble Legacy Archive Project

    NASA Astrophysics Data System (ADS)

    Kümmel, M.; Kuntschner, H.; Walsh, J. R.; Lombardi, M.; Stoehr, F.; Haase, J.; Hook, R. N.; Rosati, P.; Micol, A.; Fosbury, R.; Freudling, W.

    2009-09-01

    In 2006 the Space Telescope - European Coordinating Facility (ST-ECF), together with its partners at the STScI and the CADC, started a project to build a Hubble Legacy Archive (HLA): a collection of high-level Hubble data products and access tools to ease scientific analysis in the age of the Virtual Observatory. The ST-ECF has focused on providing extracted spectra from slitless spectroscopy HST images. The slitless NICMOS G141 data were presented at previous ADASS meetings and have already been released. In this contribution we present an overview of the ongoing project of processing the ACS/WFC G800L data which cover a larger area and contain more spectra. There are around 150 ACS/WFC G800L datasets covering an area of ˜ 600 arcmin^2, and we expect to extract and publish about 20,000 fully-calibrated spectra. We discuss the techniques and methods that were developed to automatically extract the spectra from the observations and present a selection of ACS/WFC G800L spectra as examples.

  13. Cloning, disruption, and transcriptional analysis of three RNA polymerase sigma factor genes of Streptomyces coelicolor A3(2).

    PubMed Central

    Buttner, M J; Chater, K F; Bibb, M J

    1990-01-01

    The rpoD gene of Myxococcus xanthus was used as a probe to isolate three Streptomyces coelicolor genes, hrdB, hrdC, and hrdD, which appear to encode RNA polymerase sigma factors extremely similar to the sigma 70 polypeptide of Escherichia coli. Gene disruption experiments suggested that hrdB is essential in S. coelicolor A3(2) but showed that hrdC and hrdD mutants are viable and are apparently unaffected in differentiation, gross morphology, and antibiotic production. S1 nuclease mapping showed that hrdB and hrdD, but not hrdC, were transcribed in liquid culture. The most upstream of two hrdD promoters is internal to an open reading frame (ORF X) on the opposite strand. The predicted product of this gene is homologous to the phosphinothricin acetyltransferases of Streptomyces hygroscopicus and Streptomyces viridochromogenes. The possible significance of the overlapping and divergent transcription of hrdD and ORF X is discussed. A general method for in vivo gene replacement was developed that allowed a positive selection for the desired mutants even in the absence of a mutant phenotype; it was used to isolate a stable hrdC mutant. Images PMID:2160942

  14. Subfunctionalization of Sigma Factors during the Evolution of Land Plants Based on Mutant Analysis of Liverwort (Marchantia polymorpha L.) MpSIG1

    PubMed Central

    Ueda, Minoru; Takami, Tsuneaki; Peng, Lianwei; Ishizaki, Kimitsune; Kohchi, Takayuki; Shikanai, Toshiharu; Nishimura, Yoshiki

    2013-01-01

    Sigma factor is a subunit of plastid-encoded RNA polymerase that regulates the transcription of plastid-encoded genes by recognizing a set of promoters. Sigma factors have increased in copy number and have diversified during the evolution of land plants, but details of this process remain unknown. Liverworts represent the basal group of embryophytes and are expected to retain the ancestral features of land plants. In liverwort (Marchantia polymorpha L.), we isolated and characterized a T-DNA-tagged mutant (Mpsig1) of sigma factor 1 (MpSIG1). The mutant did not show any visible phenotypes, implying that MpSIG1 function is redundant with that of other sigma factors. However, quantitative reverse-transcription polymerase chain reaction and RNA gel blot analysis revealed that genes related to photosynthesis were downregulated, resulting in the minor reduction of some protein complexes. The transcript levels of genes clustered in the petL, psaA, psbB, psbK, and psbE operons of liverwort were lower than those in the wild type, a result similar to that in the SIG1 defective mutant in rice (Oryza sativa). Overexpression analysis revealed primitive functional divergence between the SIG1 and SIG2 proteins in bryophytes, whereas these proteins still retain functional redundancy. We also discovered that the predominant sigma factor for ndhF mRNA expression has been diversified in liverwort, Arabidopsis (Arabidopsis thaliana), and rice. Our study shows the ancestral function of SIG1 and the process of functional partitioning (subfunctionalization) of sigma factors during the evolution of land plants. PMID:24025801

  15. Role of the response regulator RssB in sigma recognition and initiation of sigma proteolysis in Escherichia coli.

    PubMed

    Klauck, E; Lingnau, M; Hengge-Aronis, R

    2001-06-01

    In growing Escherichia coli cells, the master regulator of the general stress response, sigmaS (RpoS), is subject to rapid proteolysis. In response to stresses such as sudden carbon starvation, osmotic upshift or shift to acidic pH, sigmaS degradation is inhibited, sigmaS accumulates and numerous sigmaS-dependent genes with stress-protective functions are activated. sigmaS proteolysis is dependent on ClpXP protease and the response regulator RssB, whose phosphorylated form binds directly to sigmaS in vitro. Here, we show that substitutions of aspartate 58 (D58) in RssB, which result in higher sigmaS levels in vivo, produce RssB variants unable to bind sigmaS in vitro. Thus, RssB is the direct substrate recognition factor in sigmaS proteolysis, whose affinity for sigmaS depends on phosphorylation of its D58 residue. RssB does not dimerize or oligomerize upon this phosphorylation and sigmaS binding, and RssB and sigmaS exhibit a 1:1 stoichiometry in the complex. The receiver as well as the output domain of RssB are required for sigmaS binding (as shown in vivo and in vitro) and for complementation of an rssB null mutation. Thus, the N-terminal receiver domain plays an active and positive role in RssB function. Finally, we demonstrate that RssB is not co-degraded with sigmaS, i.e. RssB has a catalytic role in the initiation of sigmaS turnover. A model is presented that integrates the details of RssB-sigmaS interaction, the RssB catalytic cycle and potential stress signal input in the control of sigmaS proteolysis. PMID:11442836

  16. Six sigma.

    PubMed

    Carter, Pam

    2010-12-01

    When I was first introduced to the Six Sigma process, I resisted it with every ounce of energy I had. I continuously fabricated reasons so that I was unable to complete the training that my company required. When it came time for my performance review, I could not hide the truth from my manager; I had not completed the required training. It was then that I began my journey into the world of Six Sigma. Once I understood that a black belt and a green belt certification had nothing to do with karate, I felt much better. PMID:21117529

  17. Hyperosmotic shock induces the sigma32 and sigmaE stress regulons of Escherichia coli.

    PubMed

    Bianchi, A A; Baneyx, F

    1999-12-01

    The rise in the levels of sigmaS that accompanies hyperosmotic shock plays an important role in Escherichia coli survival by increasing the transcription of genes involved in the synthesis and transport of osmoprotectants. To determine if other stress regulons collaborate with sigmaS in dealing with high osmolality, we used single copy fusions of lacZ to representative promoters induced by protein misfolding in the cytoplasm (dnaK and ibp ), extracytoplasmic stress [P3rpoH and htrA(degP )] and cold shock (cspA). Both the sigma32-dependent, dnaK and ibp, promoters, and the sigmaE-dependent, P3rpoH and htrA, promoters were rapidly but transiently induced when mid-exponential phase cells were treated with 0.464 M sucrose. The cspA promoter, however, did not respond to the same treatment. Overproduction of the cytoplasmic domain of the sigmaE anti-sigma factor, RseA, reduced the magnitude of osmotic induction in lambdaphi(P3rpoH:lacZ ) lysogens, but had no effect on the activation of the dnaK and ibp promoters. Similarly, induction of the dnaK:lacZ and ibp:lacZ fusions was not altered in either rpoS or ompR genetic backgrounds. Osmotic upshift led to a twofold increase in the enzymatic activity of the lambdaTLF247 rpoH:lacZ translational fusion whether or not the cells were treated with rifampicin, indicating that both heat shock and exposure to high osmolality trigger a transient increase in rpoH translation. Our results suggest that the sigma32, sigmaE and sigmaS regulons closely co-operate in the managment of hyperosmotic stress. Induction of the sigma32 and sigmaE regulons appears to be an emergency response required to repair protein misfolding and facilitate the proper folding of proteins that are rapidly synthesized following loss of turgor, while providing a mechanism to increase the activity of sigmaS, the primary stress factor in osmoadaptation. PMID:10594827

  18. Genome-scale reconstruction of the sigma factor network in Escherichia coli: topology and functional states

    PubMed Central

    2014-01-01

    Background At the beginning of the transcription process, the RNA polymerase (RNAP) core enzyme requires a σ-factor to recognize the genomic location at which the process initiates. Although the crucial role of σ-factors has long been appreciated and characterized for many individual promoters, we do not yet have a genome-scale assessment of their function. Results Using multiple genome-scale measurements, we elucidated the network of σ-factor and promoter interactions in Escherichia coli. The reconstructed network includes 4,724 σ-factor-specific promoters corresponding to transcription units (TUs), representing an increase of more than 300% over what has been previously reported. The reconstructed network was used to investigate competition between alternative σ-factors (the σ70 and σ38 regulons), confirming the competition model of σ substitution and negative regulation by alternative σ-factors. Comparison with σ-factor binding in Klebsiella pneumoniae showed that transcriptional regulation of conserved genes in closely related species is unexpectedly divergent. Conclusions The reconstructed network reveals the regulatory complexity of the promoter architecture in prokaryotic genomes, and opens a path to the direct determination of the systems biology of their transcriptional regulatory networks. PMID:24461193

  19. Escherichia coli FtsH is a membrane-bound, ATP-dependent protease which degrades the heat-shock transcription factor sigma 32.

    PubMed Central

    Tomoyasu, T; Gamer, J; Bukau, B; Kanemori, M; Mori, H; Rutman, A J; Oppenheim, A B; Yura, T; Yamanaka, K; Niki, H

    1995-01-01

    Escherichia coli FtsH is an essential integral membrane protein that has an AAA-type ATPase domain at its C-terminal cytoplasmic part, which is homologous to at least three ATPase subunits of the eukaryotic 26S proteasome. We report here that FtsH is involved in degradation of the heat-shock transcription factor sigma 32, a key element in the regulation of the E. coli heat-shock response. In the temperature-sensitive ftsH1 mutant, the amount of sigma 32 at a non-permissive temperature was higher than in the wild-type under certain conditions due to a reduced rate of degradation. In an in vitro system with purified components, FtsH catalyzed ATP-dependent degradation of biologically active histidine-tagged sigma 32. FtsH has a zinc-binding motif similar to the active site of zinc-metalloproteases. Protease activity of FtsH for histidine-tagged sigma 32 was stimulated by Zn2+ and strongly inhibited by the heavy metal chelating agent o-phenanthroline. We conclude that FtsH is a novel membrane-bound, ATP-dependent metalloprotease with activity for sigma 32. These findings indicate a new mechanism of gene regulation in E. coli. Images PMID:7781608

  20. The extra-cytoplasmic function sigma factor sigX modulates biofilm and virulence-related properties in Pseudomonas aeruginosa.

    PubMed

    Gicquel, Gwendoline; Bouffartigues, Emeline; Bains, Manjeet; Oxaran, Virginie; Rosay, Thibaut; Lesouhaitier, Olivier; Connil, Nathalie; Bazire, Alexis; Maillot, Olivier; Bénard, Magalie; Cornelis, Pierre; Hancock, Robert E W; Dufour, Alain; Feuilloley, Marc G J; Orange, Nicole; Déziel, Eric; Chevalier, Sylvie

    2013-01-01

    SigX, one of the 19 extra-cytoplasmic function sigma factors of P. aeruginosa, was only known to be involved in transcription of the gene encoding the major outer membrane protein OprF. We conducted a comparative transcriptomic study between the wildtype H103 strain and its sigX mutant PAOSX, which revealed a total of 307 differentially expressed genes that differed by more than 2 fold. Most dysregulated genes belonged to six functional classes, including the "chaperones and heat shock proteins", "antibiotic resistance and susceptibility", "energy metabolism", "protein secretion/export apparatus", and "secreted factors", and "motility and attachment" classes. In this latter class, the large majority of the affected genes were down-regulated in the sigX mutant. In agreement with the array data, the sigX mutant was shown to demonstrate substantially reduced motility, attachment to biotic and abiotic surfaces, and biofilm formation. In addition, virulence towards the nematode Caenorhabditis elegans was reduced in the sigX mutant, suggesting that SigX is involved in virulence-related phenotypes. PMID:24260387

  1. Tailoring of global transcription sigma D factor by random mutagenesis to improve Escherichia coli tolerance towards low-pHs.

    PubMed

    Gao, Xi; Jiang, Ling; Zhu, Liying; Xu, Qing; Xu, Xian; Huang, He

    2016-04-20

    Bioconversion processes of organic acid or acid hydrolysis of raw material for microbial metabolism often suffer limitations as a result of microbial sensitivity in low-pH conditions. We adopted a three-step method called RAndom Insertional-deletional Strand Exchange mutagenesis (RAISE) to engineer the components of global regulator Sigma D factor (RpoD) of Escherichia coli to improve its acid tolerance. The best strain Mutant VII was identified from random mutagenesis libraries based on the growth performance, which exhibited much higher growth rate than the control (0.22h(-1) vs. 0.15h(-1)) at pH as low as 3.17. Combined transcriptome and phenome analysis of E. coli was carried out to better understand the global effects of RpoD on the regulatory networks. Our analysis showed that 95 (2.1%) of all E. coli genes were induced and 178 (4.0%) genes were repressed, including those for trehalose biosynthesis, nucleotides biosynthesis, carbon metabolism, amino acid utilization, except for acid resistance. Also regulated were the master regulators (ArcA, EvgA, H-NS and RpoS) and gene/operon-specific transcription factors (GadX, GadW, AppY, YdeO, KdgR). These results demonstrated that RpoD acts as global regulator in the growth phase of E. coli and consequently improves acid tolerances. PMID:26971973

  2. Regulated proteolysis of the alternative sigma factor SigX in Streptococcus mutans: implication in the escape from competence

    PubMed Central

    2014-01-01

    Background SigX (σX), the alternative sigma factor of Streptococcus mutans, is the key regulator for transcriptional activation of late competence genes essential for taking up exogenous DNA. Recent studies reveal that adaptor protein MecA and the protease ClpC act as negative regulators of competence by a mechanism that involves MecA-mediated proteolysis of SigX by the ClpC in S. mutans. However, the molecular detail how MecA and ClpC negatively regulate competence in this species remains to be determined. Here, we provide evidence that adaptor protein MecA targets SigX for degradation by the protease complex ClpC/ClpP when S. mutans is grown in a complex medium. Results By analyzing the cellular levels of SigX, we demonstrate that the synthesis of SigX is transiently induced by competence-stimulating peptide (CSP), but the SigX is rapidly degraded during the escape from competence. A deletion of MecA, ClpC or ClpP results in the cellular accumulation of SigX and a prolonged competence state, while an overexpression of MecA enhances proteolysis of SigX and accelerates the escape from competence. In vitro protein-protein interaction assays confirm that MecA interacts with SigX via its N-terminal domain (NTD1–82) and with ClpC via its C-terminal domain (CTD123–240). Such an interaction mediates the formation of a ternary SigX-MecA-ClpC complex, triggering the ATP-dependent degradation of SigX in the presence of ClpP. A deletion of the N-terminal or C-terminal domain of MecA abolishes its binding to SigX or ClpC. We have also found that MecA-regulated proteolysis of SigX appears to be ineffective when S. mutans is grown in a chemically defined medium (CDM), suggesting the possibility that an unknown mechanism may be involved in negative regulation of MecA-mediated proteolysis of SigX under this condition. Conclusion Adaptor protein MecA in S. mutans plays a crucial role in recognizing and targeting SigX for degradation by the protease ClpC/ClpP. Thus, Mec

  3. Sigma Factor SigB Is Crucial to Mediate Staphylococcus aureus Adaptation during Chronic Infections

    PubMed Central

    Tuchscherr, Lorena; Bischoff, Markus; Lattar, Santiago M.; Noto Llana, Mariangeles; Pförtner, Henrike; Niemann, Silke; Geraci, Jennifer; Van de Vyver, Hélène; Fraunholz, Martin J.; Cheung, Ambrose L.; Herrmann, Mathias; Völker, Uwe; Sordelli, Daniel O.; Peters, Georg; Löffler, Bettina

    2015-01-01

    Staphylococcus aureus is a major human pathogen that causes a range of infections from acute invasive to chronic and difficult-to-treat. Infection strategies associated with persisting S. aureus infections are bacterial host cell invasion and the bacterial ability to dynamically change phenotypes from the aggressive wild-type to small colony variants (SCVs), which are adapted for intracellular long-term persistence. The underlying mechanisms of the bacterial switching and adaptation mechanisms appear to be very dynamic, but are largely unknown. Here, we analyzed the role and the crosstalk of the global S. aureus regulators agr, sarA and SigB by generating single, double and triple mutants, and testing them with proteome analysis and in different in vitro and in vivo infection models. We were able to demonstrate that SigB is the crucial factor for adaptation in chronic infections. During acute infection, the bacteria require the simultaneous action of the agr and sarA loci to defend against invading immune cells by causing inflammation and cytotoxicity and to escape from phagosomes in their host cells that enable them to settle an infection at high bacterial density. To persist intracellularly the bacteria subsequently need to silence agr and sarA. Indeed agr and sarA deletion mutants expressed a much lower number of virulence factors and could persist at high numbers intracellularly. SigB plays a crucial function to promote bacterial intracellular persistence. In fact, ΔsigB-mutants did not generate SCVs and were completely cleared by the host cells within a few days. In this study we identified SigB as an essential factor that enables the bacteria to switch from the highly aggressive phenotype that settles an acute infection to a silent SCV-phenotype that allows for long-term intracellular persistence. Consequently, the SigB-operon represents a possible target to develop preventive and therapeutic strategies against chronic and therapy-refractory infections. PMID

  4. Structural Basis of DNA Recognition by the Alternative Sigma-Factor, σ54

    PubMed Central

    Doucleff, Michaeleen; Pelton, Jeffrey G.; Lee, Peter S.; Nixon, B. Tracy; Wemmer, David E.

    2007-01-01

    The σ subunit of bacterial RNA polymerase (RNAP) regulates gene expression by directing RNAP to specific promoters. Unlike σ70-type proteins, the alternative σ factor, σ54, requires interaction with an ATPase to open DNA. We present the solution structure of the C-terminal domain of σ54 bound to the –24 promoter element, in which the conserved RpoN box motif inserts into the major groove of the DNA. This structure elucidates the basis for sequence specific recognition of the –24 element, orients σ54 on the promoter, and suggests how the C-terminal domain of σ54 interacts with RNAP. PMID:17481658

  5. ATP-dependent Conformational Changes Trigger Substrate Capture and Release by an ECF-type Biotin Transporter*

    PubMed Central

    Finkenwirth, Friedrich; Sippach, Michael; Landmesser, Heidi; Kirsch, Franziska; Ogienko, Anastasia; Grunzel, Miriam; Kiesler, Cornelia; Steinhoff, Heinz-Jürgen; Schneider, Erwin; Eitinger, Thomas

    2015-01-01

    Energy-coupling factor (ECF) transporters for vitamins and metal ions in prokaryotes consist of two ATP-binding cassette-type ATPases, a substrate-specific transmembrane protein (S component) and a transmembrane protein (T component) that physically interacts with the ATPases and the S component. The mechanism of ECF transporters was analyzed upon reconstitution of a bacterial biotin transporter into phospholipid bilayer nanodiscs. ATPase activity was not stimulated by biotin and was only moderately reduced by vanadate. A non-hydrolyzable ATP analog was a competitive inhibitor. As evidenced by cross-linking of monocysteine variants and by site-specific spin labeling of the Q-helix followed by EPR-based interspin distance analyses, closure and reopening of the ATPase dimer (BioM2) was a consequence of ATP binding and hydrolysis, respectively. A previously suggested role of a stretch of small hydrophobic amino acid residues within the first transmembrane segment of the S units for S unit/T unit interactions was structurally and functionally confirmed for the biotin transporter. Cross-linking of this segment in BioY (S) using homobifunctional thiol-reactive reagents to a coupling helix of BioN (T) indicated a reorientation rather than a disruption of the BioY/BioN interface during catalysis. Fluorescence emission of BioY labeled with an environmentally sensitive fluorophore was compatible with an ATP-induced reorientation and consistent with a hypothesized toppling mechanism. As demonstrated by [3H]biotin capture assays, ATP binding stimulated substrate capture by the transporter, and subsequent ATP hydrolysis led to substrate release. Our study represents the first experimental insight into the individual steps during the catalytic cycle of an ECF transporter in a lipid environment. PMID:25991724

  6. Expression of Clostridium difficile Toxins A and B and Their Sigma Factor TcdD Is Controlled by Temperature

    PubMed Central

    Karlsson, Sture; Dupuy, Bruno; Mukherjee, Kakoli; Norin, Elisabeth; Burman, Lars G.; Åkerlund, Thomas

    2003-01-01

    Growth temperature was found to control the expression of toxins A and B in Clostridium difficile VPI 10463, with a maximum at 37°C and low levels at 22 and 42°C in both peptone yeast (PY) and defined media. The up-regulation of toxin A and B mRNA and protein levels upon temperature upshift from 22 to 37°C followed the same kinetics, showing that temperature control occurred at the level of transcription. Experiments with Clostridium perfringens using gusA as a reporter gene demonstrated that both toxin gene promoters were temperature controlled and that their high activity at 37°C was dependent on the alternative sigma factor TcdD. Furthermore, tcdD was found to be autoinduced at 37°C. Glucose down-regulated all these responses in the C. perfringens constructs, similar to its impact on toxin production in C. difficile PY broth cultures. C. difficile proteins induced at 37°C and thus coregulated with the toxins by temperature were demonstrated by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and identified as enzymes involved in butyric acid production and as electron carriers in oxidation-reduction reactions. The regulation of toxin production in C. difficile by temperature is a novel finding apparently reflecting an adaptation of the expression of its virulence to mammalian hosts. PMID:12654792

  7. The Extra-Cytoplasmic Function Sigma Factor SigX Modulates Biofilm and Virulence-Related Properties in Pseudomonas aeruginosa

    PubMed Central

    Gicquel, Gwendoline; Bouffartigues, Emeline; Bains, Manjeet; Oxaran, Virginie; Rosay, Thibaut; Lesouhaitier, Olivier; Connil, Nathalie; Bazire, Alexis; Maillot, Olivier; Bénard, Magalie; Cornelis, Pierre; Hancock, Robert E. W.; Dufour, Alain; Feuilloley, Marc G. J.; Orange, Nicole; Déziel, Eric; Chevalier, Sylvie

    2013-01-01

    SigX, one of the 19 extra-cytoplasmic function sigma factors of P. aeruginosa, was only known to be involved in transcription of the gene encoding the major outer membrane protein OprF. We conducted a comparative transcriptomic study between the wildtype H103 strain and its sigX mutant PAOSX, which revealed a total of 307 differentially expressed genes that differed by more than 2 fold. Most dysregulated genes belonged to six functional classes, including the “chaperones and heat shock proteins”, “antibiotic resistance and susceptibility”, “energy metabolism”, “protein secretion/export apparatus”, and “secreted factors”, and “motility and attachment” classes. In this latter class, the large majority of the affected genes were down-regulated in the sigX mutant. In agreement with the array data, the sigX mutant was shown to demonstrate substantially reduced motility, attachment to biotic and abiotic surfaces, and biofilm formation. In addition, virulence towards the nematode Caenorhabditis elegans was reduced in the sigX mutant, suggesting that SigX is involved in virulence-related phenotypes. PMID:24260387

  8. The Key Sigma Factor of Transition Phase, SigH, Controls Sporulation, Metabolism, and Virulence Factor Expression in Clostridium difficile▿†

    PubMed Central

    Saujet, Laure; Monot, Marc; Dupuy, Bruno; Soutourina, Olga; Martin-Verstraete, Isabelle

    2011-01-01

    Toxin synthesis in Clostridium difficile increases as cells enter into stationary phase. We first compared the expression profiles of strain 630E during exponential growth and at the onset of stationary phase and showed that genes involved in sporulation, cellular division, and motility, as well as carbon and amino acid metabolism, were differentially expressed under these conditions. We inactivated the sigH gene, which encodes an alternative sigma factor involved in the transition to post-exponential phase in Bacillus subtilis. Then, we compared the expression profiles of strain 630E and the sigH mutant after 10 h of growth. About 60% of the genes that were differentially expressed between exponential and stationary phases, including genes involved in motility, sporulation, and metabolism, were regulated by SigH, which thus appears to be a key regulator of the transition phase in C. difficile. SigH positively controls several genes required for sporulation. Accordingly, sigH inactivation results in an asporogeneous phenotype. The spo0A and CD2492 genes, encoding the master regulator of sporulation and one of its associated kinases, and the spoIIA operon were transcribed from a SigH-dependent promoter. The expression of tcdA and tcdB, encoding the toxins, and of tcdR, encoding the sigma factor required for toxin production, increased in a sigH mutant. Finally, SigH regulates the expression of genes encoding surface-associated proteins, such as the Cwp66 adhesin, the S-layer precursor, and the flagellum components. Among the 286 genes positively regulated by SigH, about 40 transcriptional units presenting a SigH consensus in their promoter regions are good candidates for direct SigH targets. PMID:21572003

  9. Decoding Biomass-Sensing Regulons of Clostridium thermocellum Alternative Sigma-I Factors in a Heterologous Bacillus subtilis Host System

    PubMed Central

    Rozman Grinberg, Inna; Garty, Yuval; Bayer, Edward A.; Shoham, Yuval; Lamed, Raphael; Borovok, Ilya

    2016-01-01

    The Gram-positive, anaerobic, cellulolytic, thermophile Clostridium (Ruminiclostridium) thermocellum secretes a multi-enzyme system called the cellulosome to solubilize plant cell wall polysaccharides. During the saccharolytic process, the enzymatic composition of the cellulosome is modulated according to the type of polysaccharide(s) present in the environment. C. thermocellum has a set of eight alternative RNA polymerase sigma (σ) factors that are activated in response to extracellular polysaccharides and share sequence similarity to the Bacillus subtilis σI factor. The aim of the present work was to demonstrate whether individual C. thermocellum σI-like factors regulate specific cellulosomal genes, focusing on C. thermocellum σI6 and σI3 factors. To search for putative σI6- and σI3-dependent promoters, bioinformatic analysis of the upstream regions of the cellulosomal genes was performed. Because of the limited genetic tools available for C. thermocellum, the functionality of the predicted σI6- and σI3-dependent promoters was studied in B. subtilis as a heterologous host. This system enabled observation of the activation of 10 predicted σI6-dependent promoters associated with the C. thermocellum genes: sigI6 (itself, Clo1313_2778), xyn11B (Clo1313_0522), xyn10D (Clo1313_0177), xyn10Z (Clo1313_2635), xyn10Y (Clo1313_1305), cel9V (Clo1313_0349), cseP (Clo1313_2188), sigI1 (Clo1313_2174), cipA (Clo1313_0627), and rsgI5 (Clo1313_0985). Additionally, we observed the activation of 4 predicted σI3-dependent promoters associated with the C. thermocellum genes: sigI3 (itself, Clo1313_1911), pl11 (Clo1313_1983), ce12 (Clo1313_0693) and cipA. Our results suggest possible regulons of σI6 and σI3 in C. thermocellum, as well as the σI6 and σI3 promoter consensus sequences. The proposed -35 and -10 promoter consensus elements of σI6 are CNNAAA and CGAA, respectively. Additionally, a less conserved CGA sequence next to the C in the -35 element and a highly

  10. Decoding Biomass-Sensing Regulons of Clostridium thermocellum Alternative Sigma-I Factors in a Heterologous Bacillus subtilis Host System.

    PubMed

    Muñoz-Gutiérrez, Iván; Ortiz de Ora, Lizett; Rozman Grinberg, Inna; Garty, Yuval; Bayer, Edward A; Shoham, Yuval; Lamed, Raphael; Borovok, Ilya

    2016-01-01

    The Gram-positive, anaerobic, cellulolytic, thermophile Clostridium (Ruminiclostridium) thermocellum secretes a multi-enzyme system called the cellulosome to solubilize plant cell wall polysaccharides. During the saccharolytic process, the enzymatic composition of the cellulosome is modulated according to the type of polysaccharide(s) present in the environment. C. thermocellum has a set of eight alternative RNA polymerase sigma (σ) factors that are activated in response to extracellular polysaccharides and share sequence similarity to the Bacillus subtilis σI factor. The aim of the present work was to demonstrate whether individual C. thermocellum σI-like factors regulate specific cellulosomal genes, focusing on C. thermocellum σI6 and σI3 factors. To search for putative σI6- and σI3-dependent promoters, bioinformatic analysis of the upstream regions of the cellulosomal genes was performed. Because of the limited genetic tools available for C. thermocellum, the functionality of the predicted σI6- and σI3-dependent promoters was studied in B. subtilis as a heterologous host. This system enabled observation of the activation of 10 predicted σI6-dependent promoters associated with the C. thermocellum genes: sigI6 (itself, Clo1313_2778), xyn11B (Clo1313_0522), xyn10D (Clo1313_0177), xyn10Z (Clo1313_2635), xyn10Y (Clo1313_1305), cel9V (Clo1313_0349), cseP (Clo1313_2188), sigI1 (Clo1313_2174), cipA (Clo1313_0627), and rsgI5 (Clo1313_0985). Additionally, we observed the activation of 4 predicted σI3-dependent promoters associated with the C. thermocellum genes: sigI3 (itself, Clo1313_1911), pl11 (Clo1313_1983), ce12 (Clo1313_0693) and cipA. Our results suggest possible regulons of σI6 and σI3 in C. thermocellum, as well as the σI6 and σI3 promoter consensus sequences. The proposed -35 and -10 promoter consensus elements of σI6 are CNNAAA and CGAA, respectively. Additionally, a less conserved CGA sequence next to the C in the -35 element and a highly

  11. Stress sigma factor RpoS degradation and translation are sensitive to the state of central metabolism.

    PubMed

    Battesti, Aurelia; Majdalani, Nadim; Gottesman, Susan

    2015-04-21

    RpoS, the stationary phase/stress sigma factor of Escherichia coli, regulates a large cohort of genes important for the cell to deal with suboptimal conditions. Its level increases quickly in the cell in response to many stresses and returns to low levels when growth resumes. Increased RpoS results from increased translation and decreased RpoS degradation. Translation is positively regulated by small RNAs (sRNAs). Protein stability is positively regulated by anti-adaptors, which prevent the RssB adaptor-mediated degradation of RpoS by the ClpXP protease. Inactivation of aceE, a subunit of pyruvate dehydrogenase (PDH), was found to increase levels of RpoS by affecting both translation and protein degradation. The stabilization of RpoS in aceE mutants is dependent on increased transcription and translation of IraP and IraD, two known anti-adaptors. The aceE mutation also leads to a significant increase in rpoS translation. The sRNAs known to positively regulate RpoS are not responsible for the increased translation; sequences around the start codon are sufficient for the induction of translation. PDH synthesizes acetyl-CoA; acetate supplementation allows the cell to synthesize acetyl-CoA by an alternative, less favored pathway, in part dependent upon RpoS. Acetate addition suppressed the effects of the aceE mutant on induction of the anti-adaptors, RpoS stabilization, and rpoS translation. Thus, the bacterial cell responds to lowered levels of acetyl-CoA by inducing RpoS, allowing reprogramming of E. coli metabolism. PMID:25847996

  12. Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope

    PubMed Central

    Tsai, Shang-Yi A.; Chuang, Jian-Ying; Tsai, Meng-Shan; Wang, Xiao-fei; Hung, Jan-Jong; Chang, Wen-Chang; Bonci, Antonello; Su, Tsung-Ping

    2015-01-01

    The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER–mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal. PMID:26554014

  13. Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope.

    PubMed

    Tsai, Shang-Yi A; Chuang, Jian-Ying; Tsai, Meng-Shan; Wang, Xiao-Fei; Xi, Zheng-Xiong; Hung, Jan-Jong; Chang, Wen-Chang; Bonci, Antonello; Su, Tsung-Ping

    2015-11-24

    The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER-mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal. PMID:26554014

  14. The Sigma Factor AlgU Plays a Key Role in Formation of Robust Biofilms by Nonmucoid Pseudomonas aeruginosa▿

    PubMed Central

    Bazire, Alexis; Shioya, Kouki; Soum-Soutéra, Emmanuelle; Bouffartigues, Emeline; Ryder, Cynthia; Guentas-Dombrowsky, Linda; Hémery, Gaëlle; Linossier, Isabelle; Chevalier, Sylvie; Wozniak, Daniel J.; Lesouhaitier, Olivier; Dufour, Alain

    2010-01-01

    The extracytoplasmic function sigma factor AlgU of Pseudomonas aeruginosa is responsible for alginate overproduction, leading to mucoidy and chronic infections of cystic fibrosis patients. We investigated here the role of AlgU in the formation of nonmucoid biofilms. The algU mutant of P. aeruginosa PAO1 (PAOU) showed a dramatic impairment in biofilm formation under dynamic conditions. PAOU was defective both in cell attachment to glass and in development of robust, shear-resistant biofilms. This was explained by an impaired production of extracellular matrix, specifically of the exopolysaccharide Psl, as revealed by microscopy and enzyme-linked immunosorbent assay. Complementing the algU mutation with a plasmid-borne algU gene restored wild-type phenotypes. Compared with that in PAO1, expression of the psl operon was reduced in the PAOU strain, and the biofilm formation ability of this strain was partially restored by inducing the transcription of the psl operon. Furthermore, expression of the lectin-encoding lecA and lecB genes was reduced in the PAOU strain. In agreement with the requirement of LecB for type IV pilus biogenesis, PAOU displayed impaired twitching motility. Collectively, these genetic downregulation events explain the biofilm formation defect of the PAOU mutant. Promoter mapping indicated that AlgU is probably not directly responsible for transcription of the psl operon and the lec genes, but AlgU is involved in the expression of the ppyR gene, whose product was reported to positively control psl expression. Expressing the ppyR gene in PAOU partially restored the formation of robust biofilms. PMID:20348252

  15. Stress sigma factor RpoS degradation and translation are sensitive to the state of central metabolism

    PubMed Central

    Battesti, Aurelia; Majdalani, Nadim; Gottesman, Susan

    2015-01-01

    RpoS, the stationary phase/stress sigma factor of Escherichia coli, regulates a large cohort of genes important for the cell to deal with suboptimal conditions. Its level increases quickly in the cell in response to many stresses and returns to low levels when growth resumes. Increased RpoS results from increased translation and decreased RpoS degradation. Translation is positively regulated by small RNAs (sRNAs). Protein stability is positively regulated by anti-adaptors, which prevent the RssB adaptor-mediated degradation of RpoS by the ClpXP protease. Inactivation of aceE, a subunit of pyruvate dehydrogenase (PDH), was found to increase levels of RpoS by affecting both translation and protein degradation. The stabilization of RpoS in aceE mutants is dependent on increased transcription and translation of IraP and IraD, two known anti-adaptors. The aceE mutation also leads to a significant increase in rpoS translation. The sRNAs known to positively regulate RpoS are not responsible for the increased translation; sequences around the start codon are sufficient for the induction of translation. PDH synthesizes acetyl-CoA; acetate supplementation allows the cell to synthesize acetyl-CoA by an alternative, less favored pathway, in part dependent upon RpoS. Acetate addition suppressed the effects of the aceE mutant on induction of the anti-adaptors, RpoS stabilization, and rpoS translation. Thus, the bacterial cell responds to lowered levels of acetyl-CoA by inducing RpoS, allowing reprogramming of E. coli metabolism. PMID:25847996

  16. Self-cleavage of the Pseudomonas aeruginosa Cell-surface Signaling Anti-sigma Factor FoxR Occurs through an N-O Acyl Rearrangement.

    PubMed

    Bastiaansen, Karlijn C; van Ulsen, Peter; Wijtmans, Maikel; Bitter, Wilbert; Llamas, María A

    2015-05-01

    The Fox system of Pseudomonas aeruginosa is a cell-surface signaling (CSS) pathway employed by the bacterium to sense and respond to the presence of the heterologous siderophore ferrioxamine in the environment. This regulatory pathway controls the transcription of the foxA ferrioxamine receptor gene through the extracytoplasmic function sigma factor σ(FoxI). In the absence of ferrioxamine, the activity of σ(FoxI) is inhibited by the transmembrane anti-sigma factor FoxR. Upon binding of ferrioxamine by the FoxA receptor, FoxR is processed by a complex proteolytic cascade leading to the release and activation of σ(FoxI). Interestingly, we have recently shown that FoxR undergoes self-cleavage between the periplasmic Gly-191 and Thr-192 residues independent of the perception of ferrioxamine. This autoproteolytic event, which is widespread among CSS anti-sigma factors, produces two distinct domains that interact and function together to transduce the presence of the signal. In this work, we provide evidence that the self-cleavage of FoxR is not an enzyme-dependent process but is induced by an N-O acyl rearrangement. Mutation analysis showed that the nucleophilic side chain of the Thr-192 residue at +1 of the cleavage site is required for an attack on the preceding Gly-191, after which the resulting ester bond is likely hydrolyzed. Because the cleavage site is well preserved and the hydrolysis of periplasmic CSS anti-sigma factors is widely observed, we hypothesize that cleavage via an N-O acyl rearrangement is a conserved feature of these proteins. PMID:25809487

  17. Global Repression of Host-Associated Genes of the Lyme Disease Spirochete through Post-Transcriptional Modulation of the Alternative Sigma Factor RpoS

    PubMed Central

    Dulebohn, Daniel P.; Hayes, Beth M.; Rosa, Patricia A.

    2014-01-01

    Borrelia burgdorferi, the agent of Lyme disease, is a vector-borne pathogen that transits between Ixodes ticks and vertebrate hosts. During the natural infectious cycle, spirochetes must globally adjust their transcriptome to survive in these dissimilar environments. One way B. burgdorferi accomplishes this is through the use of alternative sigma factors to direct transcription of specific genes. RpoS, one of only three sigma factors in B. burgdorferi, controls expression of genes required during tick-transmission and infection of the mammalian host. How spirochetes switch between different sigma factors during the infectious cycle has remained elusive. Here we establish a role for a novel protein, BBD18, in the regulation of the virulence-associated sigma factor RpoS. Constitutive expression of BBD18 repressed transcription of RpoS-dependent genes to levels equivalent to those observed in an rpoS mutant. Consistent with the global loss of RpoS-dependent transcripts, we were unable to detect RpoS protein. However, constitutive expression of BBD18 did not diminish the amount of rpoS transcript, indicating post-transcriptional regulation of RpoS by BBD18. Interestingly, BBD18-mediated repression of RpoS is independent of both the rpoS promoter and the 5’ untranslated region, suggesting a mechanism of protein destabilization rather than translational control. We propose that BBD18 is a novel regulator of RpoS and its activity likely represents a first step in the transition from an RpoS-ON to an RpoS-OFF state, when spirochetes transition from the host to the tick vector. PMID:24671196

  18. Self-cleavage of the Pseudomonas aeruginosa Cell-surface Signaling Anti-sigma Factor FoxR Occurs through an N-O Acyl Rearrangement*

    PubMed Central

    Bastiaansen, Karlijn C.; van Ulsen, Peter; Wijtmans, Maikel; Bitter, Wilbert; Llamas, María A.

    2015-01-01

    The Fox system of Pseudomonas aeruginosa is a cell-surface signaling (CSS) pathway employed by the bacterium to sense and respond to the presence of the heterologous siderophore ferrioxamine in the environment. This regulatory pathway controls the transcription of the foxA ferrioxamine receptor gene through the extracytoplasmic function sigma factor σFoxI. In the absence of ferrioxamine, the activity of σFoxI is inhibited by the transmembrane anti-sigma factor FoxR. Upon binding of ferrioxamine by the FoxA receptor, FoxR is processed by a complex proteolytic cascade leading to the release and activation of σFoxI. Interestingly, we have recently shown that FoxR undergoes self-cleavage between the periplasmic Gly-191 and Thr-192 residues independent of the perception of ferrioxamine. This autoproteolytic event, which is widespread among CSS anti-sigma factors, produces two distinct domains that interact and function together to transduce the presence of the signal. In this work, we provide evidence that the self-cleavage of FoxR is not an enzyme-dependent process but is induced by an N-O acyl rearrangement. Mutation analysis showed that the nucleophilic side chain of the Thr-192 residue at +1 of the cleavage site is required for an attack on the preceding Gly-191, after which the resulting ester bond is likely hydrolyzed. Because the cleavage site is well preserved and the hydrolysis of periplasmic CSS anti-sigma factors is widely observed, we hypothesize that cleavage via an N-O acyl rearrangement is a conserved feature of these proteins. PMID:25809487

  19. Crystallization and preliminary X-ray diffraction studies of two domains of a bilobed extra-cytoplasmic function sigma factor SigC from Mycobacterium tuberculosis

    SciTech Connect

    Thakur, Krishan Gopal; Gopal, B.

    2005-08-01

    Expression, purification and preliminary X-ray diffraction studies of the two domains of the sigma factor SigC from M. tuberculosis are reported. Sigma factors are transcription-regulatory proteins that bind to RNA polymerase and facilitate promoter recognition. The so-called extracytoplasmic function sigma factors help a bacterium to respond to environmental conditions. Mycobacterium tuberculosis SigC (σ{sup C}) is an extracytoplasmic sigma factor that is essential for lethality in a mouse model of infection and is conserved in all pathogenic mycobacterial species. This protein consists of two domains that are connected by an ∼25-amino-acid linker. The N-terminal domain contains the σ{sub 2} DNA-binding motif, whereas the σ{sub 4} motif is located in the C-terminal domain. Native σ{sup C} did not yield diffraction-quality crystals. However, two of its domains have been cloned, expressed and crystallized: σ{sub 2}{sup C} (12.3 kDa) and σ{sub c}{sup C} (7.5 kDa). The σ{sub c}{sup C} crystals belong to the hexagonal space group P6{sub 1}, with unit-cell parameters a = b = 85.28, c = 79.63 Å, and native X-ray diffraction data were collected from this domain to 2.7 Å on an in-house X-ray home source. The σ{sub 4}{sup C} crystals belong to the cubic space group F23, with unit-cell parameters a = b = c = 161.21 Å. X-ray diffraction data were collected from this domain to 3.1 Å, also on an in-house X-ray source.

  20. 14-3-3 sigma and 14-3-3 zeta plays an opposite role in cell growth inhibition mediated by transforming growth factor-beta 1.

    PubMed

    Hong, Hye-Young; Jeon, Woo-Kwang; Bae, Eun-Jin; Kim, Shin-Tae; Lee, Ho-Jae; Kim, Seong-Jin; Kim, Byung-Chul

    2010-03-01

    The expression of 14-3-3 proteins is dysregulated in various types of cancer. This study was undertaken to investigate the effects of 14-3-3 zeta and 14-3-3 sigma on cell growth inhibition mediated by transforming growth factor-beta 1 (TGF-beta1). Mouse mammary epithelial cells (Eph4) that are transformed with oncogenic c-H-Ras (EpRas) and no longer sensitive to TGF-beta1-mediated growth inhibition displayed increased expression of 14-3-3 zeta and decreased expression of 14-3-3 sigma compared with parental Eph4 cells. Using small interfering RNA-mediated knockdown and overexpression of 14-3-3 sigma or 14-3-3 zeta, we showed that 14-3-3 sigma is required for TGF-beta1-mediated growth inhibition whereas 14-3-3 zeta negatively modulates this growth inhibitory response. Notably, overexpression of 14-3-3 zeta increased the level of Smad3 protein that is phosphorylated at linker regions and cannot mediate the TGF-beta1 growth inhibitory response. Consistent with this finding, mutation of the 14-3-3 zeta phosphorylation sites in Smad3 markedly reduced the 14-3-3 zeta-mediated inhibition of TGF-beta1-induced p15 promoter-reporter activity and cell cycle arrest, suggesting that these residues are critical targets of 14-3-3 zeta in the suppression of TGF-beta1-mediated growth. Taken together, our findings indicate that dysregulation of 14-3-3 sigma or 14-3-3 zeta contributes to TGF-beta1 resistance in cancer cells. PMID:20082218

  1. Mutations in the Primary Sigma Factor σA and Termination Factor Rho That Reduce Susceptibility to Cell Wall Antibiotics

    PubMed Central

    Lee, Yong Heon

    2014-01-01

    Combinations of glycopeptides and β-lactams exert synergistic antibacterial activity, but the evolutionary mechanisms driving resistance to both antibiotics remain largely unexplored. By repeated subculturing with increasing vancomycin (VAN) and cefuroxime (CEF) concentrations, we isolated an evolved strain of the model bacterium Bacillus subtilis with reduced susceptibility to both antibiotics. Whole-genome sequencing revealed point mutations in genes encoding the major σ factor of RNA polymerase (sigA), a cell shape-determining protein (mreB), and the ρ termination factor (rho). Genetic-reconstruction experiments demonstrated that the G-to-C substitution at position 336 encoded by sigA (sigAG336C), in the domain that recognizes the −35 promoter region, is sufficient to reduce susceptibility to VAN and works cooperatively with the rhoG56C substitution to increase CEF resistance. Transcriptome analyses revealed that the sigAG336C substitution has wide-ranging effects, including elevated expression of the general stress σ factor (σB) regulon, which is required for CEF resistance, and decreased expression of the glpTQ genes, which leads to fosfomycin (FOS) resistance. Our findings suggest that mutations in the core transcriptional machinery may facilitate the evolution of resistance to multiple cell wall antibiotics. PMID:25112476

  2. An Aromatic Cap Seals the Substrate Binding Site in an ECF-Type S Subunit for Riboflavin.

    PubMed

    Karpowich, Nathan K; Song, Jinmei; Wang, Da-Neng

    2016-07-31

    ECF transporters are a family of active membrane transporters for essential micronutrients, such as vitamins and trace metals. Found exclusively in archaea and bacteria, these transporters are composed of four subunits: an integral membrane substrate-binding subunit (EcfS), a transmembrane coupling subunit (EcfT), and two ATP-binding cassette ATPases (EcfA and EcfA'). We have characterized the structural basis of substrate binding by the EcfS subunit for riboflavin from Thermotoga maritima, TmRibU. TmRibU binds riboflavin with high affinity, and the protein-substrate complex is exceptionally stable in solution. The crystal structure of riboflavin-bound TmRibU reveals an electronegative binding pocket at the extracellular surface in which the substrate is completely buried. Analysis of the intermolecular contacts indicates that nearly every available substrate hydrogen bond is satisfied. A conserved aromatic residue at the extracellular end of TM5, Tyr130, caps the binding site to generate a substrate-bound, occluded state, and non-conservative mutation of Tyr130 reduces the stability of this conformation. Using a novel fluorescence binding assay, we find that an aromatic residue at this position is essential for high-affinity substrate binding. Comparison with other S subunit structures suggests that TM5 and Loop5-6 contain a dynamic, conserved motif that plays a key role in gating substrate entry and release by S subunits of ECF transporters. PMID:27312125

  3. Responsibility Factors of Reducing Inefficiencies in Information System Processes and Their Role on Intention to Acquire Six Sigma Certification

    ERIC Educational Resources Information Center

    Hejazi, Sara

    2009-01-01

    Organizations worldwide have been turning to Six Sigma program (SSP) to eliminate the defects in their products or drive out the variability in their processes to attain a competitive advantage in their marketplace. An effective certification program has been touted as a major contributor to successful implementation of SSP. An effective…

  4. 75 FR 43801 - Airworthiness Directives; Eurocopter France (ECF) Model EC225LP Helicopters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-27

    ...We are adopting a new airworthiness directive (AD) for the specified ECF Model EC225LP helicopters. This AD results from a mandatory continuing airworthiness information (MCAI) AD issued by the aviation authority of the European Aviation Safety Agency (EASA), which is the Technical Agent for the Member States of the European Community. The MCAI AD states there have been a ``few'' reports of......

  5. Group 3 sigma factor gene, sigJ, a key regulator of desiccation tolerance, regulates the synthesis of extracellular polysaccharide in cyanobacterium Anabaena sp. strain PCC 7120

    PubMed Central

    Yoshimura, Hidehisa; Okamoto, Shinobu; Tsumuraya, Yoichi; Ohmori, Masayuki

    2007-01-01

    Abstract The changes in the expression of sigma factor genes during dehydration in terrestrial Nostoc HK-01 and aquatic Anabaena PCC 7120 were determined. The expression of the sigJ gene in terrestrial Nostoc HK-01, which is homologous to sigJ (alr0277) in aquatic Anabaena PCC 7120, was significantly induced in the mid-stage of dehydration. We constructed a higher-expressing transformant of the sigJ gene (HE0277) in Anabaena PCC 7120, and the transformant acquired desiccation tolerance. The results of Anabaena oligonucleotide microarray experiments showed that a comparatively large number of genes relating to polysaccharide biosynthesis were upregulated in the HE0277 cells. The extracellular polysaccharide released into the culture medium of the HE0277 cells was as much as 3.2-fold more than that released by the control cells. This strongly suggests that the group 3 sigma factor gene sigJ is fundamental and conducive to desiccation tolerance in these cyanobacteria. PMID:17376888

  6. Indirect positive effects of a sigma factor RpoN deletion on the lactate-based polymer production in Escherichia coli.

    PubMed

    Kadoya, Ryosuke; Kodama, Yu; Matsumoto, Ken'ichiro; Taguchi, Seiichi

    2015-01-01

    The production of bacterial polyesters, polyhydroxyalkanoates (PHAs), has been improved by several rational approaches such as overexpression and/or engineering of the enzymes directly related to PHA biosynthetic pathways. In this study, a new approach at transcription level has been applied to a new category of the copolymer of lactate (LA) and 3-hydroxybutyrate (3HB), P(LA-co-3HB). When the 4 disrupting mutants of sigma factors in Escherichia coli, rpoN, rpoS, fliA, fecI, were used as platforms for production of P(LA-co-3HB), increases in the production level and LA fraction of the copolymer were observed for the mutant strain with rpoN disruption. These positive impacts on the polymer production were caused in an "indirect manner" via changes in the multiple genes governed by RpoN. A genome-wide engineering by sigma factors would be a versatile approach for the production of value-added products of interest and available for combination with the other beneficial tools. PMID:26218242

  7. Indirect positive effects of a sigma factor RpoN deletion on the lactate-based polymer production in Escherichia coli

    PubMed Central

    Kadoya, Ryosuke; Kodama, Yu; Matsumoto, Ken'ichiro; Taguchi, Seiichi

    2015-01-01

    The production of bacterial polyesters, polyhydroxyalkanoates (PHAs), has been improved by several rational approaches such as overexpression and/or engineering of the enzymes directly related to PHA biosynthetic pathways. In this study, a new approach at transcription level has been applied to a new category of the copolymer of lactate (LA) and 3-hydroxybutyrate (3HB), P(LA-co-3HB). When the 4 disrupting mutants of sigma factors in Escherichia coli, rpoN, rpoS, fliA, fecI, were used as platforms for production of P(LA-co-3HB), increases in the production level and LA fraction of the copolymer were observed for the mutant strain with rpoN disruption. These positive impacts on the polymer production were caused in an “indirect manner” via changes in the multiple genes governed by RpoN. A genome-wide engineering by sigma factors would be a versatile approach for the production of value-added products of interest and available for combination with the other beneficial tools. PMID:26218242

  8. Sigma factor selectivity in Borrelia burgdorferi: RpoS recognition of the ospE/ospF/elp promoters is dependent on the sequence of the -10 region.

    PubMed

    Eggers, Christian H; Caimano, Melissa J; Radolf, Justin D

    2006-03-01

    Members of the ospE/ospF/elp lipoprotein gene families of Borrelia burgdorferi, the Lyme disease agent, are transcriptionally upregulated in response to the influx of blood into the midgut of an infected tick. We recently have demonstrated that despite the high degree of similarity between the promoters of the ospF (P(ospF)) and ospE (P(ospE)) genes of B. burgdorferi strain 297, the differential expression of ospF is RpoS-dependent, while ospE is controlled by sigma(70). Herein we used wild-type and RpoS-deficient strains of B. burgdorferi and Escherichia coli to analyse transcriptional reporters consisting of a green fluorescent protein (gfp) gene fused to P(ospF), P(ospE), or two hybrid promoters in which the -10 regions of P(ospF) and P(ospE) were switched [P(ospF ) ((E - 10)) and P(ospE) ((F - 10)) respectively]. We found that the P(ospF)-10 region is both necessary and sufficient for RpoS-dependent recognition in B. burgdorferi, while sigma(70) specificity for P(ospE) is dependent on elements outside of the -10 region. In E. coli, sigma factor selectivity for these promoters was much more permissive, with expression of each being primarily due to sigma(70). Alignment of the sequences upstream of each of the ospE/ospF/elp genes from B. burgdorferi strains 297 and B31 revealed that two B31 ospF paralogues [erpK (BBM38) and erpL (BBO39)] have -10 regions virtually identical to that of P(ospF). Correspondingly, expression of gfp reporters based on the erpK and erpL promoters was RpoS-dependent. Thus, the sequence of the P(ospF)-10 region appears to serve as a motif for RpoS recognition, the first described for any B. burgdorferi promoter. Taken together, our data support the notion that B. burgdorferi utilizes sequence differences at the -10 region as one mechanism for maintaining the transcriptional integrity of RpoS-dependent and -independent genes activated at the onset of tick feeding. PMID:16553889

  9. The Rsb Phosphoregulatory Network Controls Availability of the Primary Sigma Factor in Chlamydia trachomatis and Influences the Kinetics of Growth and Development

    PubMed Central

    Thompson, Christopher C.; Griffiths, Cherry; Nicod, Sophie S.; Lowden, Nicole M.; Wigneshweraraj, Sivaramesh; Fisher, Derek J.; McClure, Myra O.

    2015-01-01

    Chlamydia trachomatis is an obligate intracellular human pathogen that exhibits stage-specific gene transcription throughout a biphasic developmental cycle. The mechanisms that control modulation in transcription and associated phenotypic changes are poorly understood. This study provides evidence that a switch-protein kinase regulatory network controls availability of σ66, the main sigma subunit for transcription in Chlamydia. In vitro analysis revealed that a putative switch-protein kinase regulator, RsbW, is capable of interacting directly with σ66, as well as phosphorylating its own antagonist, RsbV1, rendering it inactive. Conversely, the putative PP2C-like phosphatase domain of chlamydial RsbU was capable of reverting RsbV1 into its active state. Recent advances in genetic manipulation of Chlamydia were employed to inactivate rsbV1, as well as to increase the expression levels of rsbW or rsbV1, in vivo. Representative σ66-dependent gene transcription was repressed in the absence of rsbV1 or upon increased expression of RsbW, and increased upon elevated expression of RsbV1. These effects on housekeeping transcription were also correlated to several measures of growth and development. A model is proposed where the relative levels of active antagonist (RsbV1) and switch-protein anti-sigma factor (RsbW) control the availability of σ66 and subsequently act as a molecular 'throttle' for Chlamydia growth and development. PMID:26313645

  10. The associated factors to endometrial cavity fluid and the relevant impact on the IVF-ET outcome

    PubMed Central

    2010-01-01

    Background Endometrial cavity fluid (ECF) is a fluid accumulation within the endometrial cavity. The significance of ECF remains unclear during the program of in vitro fertilization-embryo transfer (IVF-ET). The aim of the present study was to investigate the associated factors to ECF, visualized through ultrasound at the day of oocyte retrieval, and the relevant impact on the outcome of IVF-ET. Methods From the clinical data of 1557 infertility patients for IVF-ET program, 46 ECF patients were retrospectively selected as the ECF group; and another 134 patients with a bilateral salpingectomy and without ECF, selected as the control group. The demographics and the outcome of IVF-ET were compared between the two groups. Results The incidence of ECF was 2.95% (46/1557). Over half (28/46, 60.87%) of ECF patients had tubal infertility. Only 12 Of 46 ECF patients (26.09%) had visible hydrosalpinx on ultrasonography before ovarian stimulation. The cycle cancellation rate (4/46, 8.69%) of ECF group was not significantly higher than that of the control group (6/134, 4.48%; P > 0.05). Reasons for cycle cancellation in both groups were all the high risk of ovarian hyperstimulation syndrome (OHSS). No significant difference was found in clinical pregnancy rate between the patients with their ECF <3.5 mm in the anterior-posterior diameter (APD) and the control group (35.48% versus 30.47%; P > 0.05). No clinical pregnancy was found among those patients with their ECF equal or higher 3.5 mm in APD. Conclusions It was tubal infertility, not hydrosalpinx, which was related to the development of ECF. Excessive ECF (equal or higher 3.5 mm in APD) at the day of oocyte retrieval would have a negative impact on the outcome of IVF-ET. PMID:20465847

  11. ςBldN, an Extracytoplasmic Function RNA Polymerase Sigma Factor Required for Aerial Mycelium Formation in Streptomyces coelicolor A3(2)

    PubMed Central

    Bibb, Maureen J.; Molle, Virginie; Buttner, Mark J.

    2000-01-01

    Sporulation mutants of Streptomyces coelicolor appear white because they are defective in the synthesis of the gray polyketide spore pigment, and such white (whi) mutants have been used to define 13 sporulation loci. whiN, one of five new whi loci identified in a recent screen of NTG (N-methyl-N′-nitro-N-nitrosoguanidine)-induced whi strains (N. J. Ryding et al., J. Bacteriol. 181:5419–5425, 1999), was defined by two mutants, R112 and R650. R650 produced frequent spores that were longer than those of the wild type. In contrast, R112 produced long, straight, undifferentiated hyphae, although rare spore chains were observed, sometimes showing highly irregular septum placement. Subcloning and sequencing showed that whiN encodes a member of the extracytoplasmic function subfamily of RNA polymerase sigma factors and that the sigma factor has an unusual N-terminal extension of approximately 86 residues that is not present in other sigma factors. A constructed whiN null mutant failed to form aerial mycelium (the “bald” phenotype) and, as a consequence, whiN was renamed bldN. This observation was not totally unexpected because, on some media, the R112 point mutant produced substantially less aerial mycelium than its parent, M145. The bldN null mutant did not fit simply into the extracellular signaling cascade proposed for S. coelicolor bld mutants. Expression of bldN was analyzed during colony development in wild-type and aerial mycelium-deficient bld strains. bldN was transcribed from a single promoter, bldNp. bldN transcription was developmentally regulated, commencing approximately at the time of aerial mycelium formation, and depended on bldG and bldH, but not on bldA, bldB, bldC, bldF, bldK, or bldJ or on bldN itself. Transcription from the p1 promoter of the response-regulator gene bldM depended on bldN in vivo, and the bldMp1 promoter was shown to be a direct biochemical target for ςBldN holoenzyme in vitro. PMID:10913095

  12. The Sigma Factor AlgU (AlgT) Controls Exopolysaccharide Production and Tolerance towards Desiccation and Osmotic Stress in the Biocontrol Agent Pseudomonas fluorescens CHA0

    PubMed Central

    Schnider-Keel, Ursula; Lejbølle, Kirsten Bang; Baehler, Eric; Haas, Dieter; Keel, Christoph

    2001-01-01

    A variety of stress situations may affect the activity and survival of plant-beneficial pseudomonads added to soil to control root diseases. This study focused on the roles of the sigma factor AlgU (synonyms, AlgT, RpoE, and ς22) and the anti-sigma factor MucA in stress adaptation of the biocontrol agent Pseudomonas fluorescens CHA0. The algU-mucA-mucB gene cluster of strain CHA0 was similar to that of the pathogens Pseudomonas aeruginosa and Pseudomonas syringae. Strain CHA0 is naturally nonmucoid, whereas a mucA deletion mutant or algU-overexpressing strains were highly mucoid due to exopolysaccharide overproduction. Mucoidy strictly depended on the global regulator GacA. An algU deletion mutant was significantly more sensitive to osmotic stress than the wild-type CHA0 strain and the mucA mutant were. Expression of an algU′-′lacZ reporter fusion was induced severalfold in the wild type and in the mucA mutant upon exposure to osmotic stress, whereas a lower, noninducible level of expression was observed in the algU mutant. Overexpression of algU did not enhance tolerance towards osmotic stress. AlgU was found to be essential for tolerance of P. fluorescens towards desiccation stress in a sterile vermiculite-sand mixture and in a natural sandy loam soil. The size of the population of the algU mutant declined much more rapidly than the size of the wild-type population at soil water contents below 5%. In contrast to its role in pathogenic pseudomonads, AlgU did not contribute to tolerance of P. fluorescens towards oxidative and heat stress. In conclusion, AlgU is a crucial determinant in the adaptation of P. fluorescens to dry conditions and hyperosmolarity, two major stress factors that limit bacterial survival in the environment. PMID:11722923

  13. Domain movements of the enhancer-dependent sigma factor drive DNA delivery into the RNA polymerase active site: insights from single molecule studies

    PubMed Central

    Sharma, Amit; Leach, Robert N.; Gell, Christopher; Zhang, Nan; Burrows, Patricia C.; Shepherd, Dale A.; Wigneshweraraj, Sivaramesh; Smith, David Alastair; Zhang, Xiaodong; Buck, Martin; Stockley, Peter G.; Tuma, Roman

    2014-01-01

    Recognition of bacterial promoters is regulated by two distinct classes of sequence-specific sigma factors, σ70 or σ54, that differ both in their primary sequence and in the requirement of the latter for activation via enhancer-bound upstream activators. The σ54 version controls gene expression in response to stress, often mediating pathogenicity. Its activator proteins are members of the AAA+ superfamily and use adenosine triphosphate (ATP) hydrolysis to remodel initially auto-inhibited holoenzyme promoter complexes. We have mapped this remodeling using single-molecule fluorescence spectroscopy. Initial remodeling is nucleotide-independent and driven by binding both ssDNA during promoter melting and activator. However, DNA loading into the RNA polymerase active site depends on co-operative ATP hydrolysis by the activator. Although the coupled promoter recognition and melting steps may be conserved between σ70 and σ54, the domain movements of the latter have evolved to require an activator ATPase. PMID:24553251

  14. Domain movements of the enhancer-dependent sigma factor drive DNA delivery into the RNA polymerase active site: insights from single molecule studies.

    PubMed

    Sharma, Amit; Leach, Robert N; Gell, Christopher; Zhang, Nan; Burrows, Patricia C; Shepherd, Dale A; Wigneshweraraj, Sivaramesh; Smith, David Alastair; Zhang, Xiaodong; Buck, Martin; Stockley, Peter G; Tuma, Roman

    2014-04-01

    Recognition of bacterial promoters is regulated by two distinct classes of sequence-specific sigma factors, σ(70) or σ(54), that differ both in their primary sequence and in the requirement of the latter for activation via enhancer-bound upstream activators. The σ(54) version controls gene expression in response to stress, often mediating pathogenicity. Its activator proteins are members of the AAA+ superfamily and use adenosine triphosphate (ATP) hydrolysis to remodel initially auto-inhibited holoenzyme promoter complexes. We have mapped this remodeling using single-molecule fluorescence spectroscopy. Initial remodeling is nucleotide-independent and driven by binding both ssDNA during promoter melting and activator. However, DNA loading into the RNA polymerase active site depends on co-operative ATP hydrolysis by the activator. Although the coupled promoter recognition and melting steps may be conserved between σ(70) and σ(54), the domain movements of the latter have evolved to require an activator ATPase. PMID:24553251

  15. Preparation and preliminary X-ray diffraction analysis of crystals of bacterial flagellar sigma factor σ{sup 28} in complex with the σ{sup 28}-binding region of its antisigma factor, FlgM

    SciTech Connect

    Okada, Kengo; Ichihara, Hisako; Takahashi, Hiroyuki; Fujita, Nobuyuki; Ishihama, Akira; Hakoshima, Toshio

    2007-03-01

    A complex of E. coli flagellar and chemotaxis-specific sigma factor σ{sup 28} bound to the σ{sup 28}-binding region of its antisigma factor FlgM was crystallized. Diffraction data were collected to a resolution of 2.7 Å. The sigma 28 kDa (σ{sup 28}) factor is a transcription factor specific for the expression of bacterial flagellar and chemotaxis genes. Its antisigma factor, FlgM, binds σ{sup 28} factor and inhibits its activity as a transcription factor. In this study, crystals of the complex between Escherichia coli σ{sup 28} and the C-terminal σ{sup 28}-binding region of FlgM were obtained. The crystals belong to space group P3{sub 1}21 or P3{sub 2}21, with unit-cell parameters a = b = 106.7 (2), c = 51.74 (3) Å, containing one complex in the crystallographic asymmetric unit. An X-ray intensity data set was collected to a resolution of 2.7 Å.

  16. Expression of the translocator protein (TSPO) from Pseudomonas fluorescens Pf0-1 requires the stress regulatory sigma factors AlgU and RpoH.

    PubMed

    Leneveu-Jenvrin, Charlène; Bouffartigues, Emeline; Maillot, Olivier; Cornelis, Pierre; Feuilloley, Marc G J; Connil, Nathalie; Chevalier, Sylvie

    2015-01-01

    The translocator protein (TSPO), previously designated as peripheral-type benzodiazepine receptor, is an evolutionary conserved protein that is found in many Eukarya, Archae, and Bacteria, in which it plays several important functions including for example membrane biogenesis, signaling, and stress response. A tspo homolog gene has been identified in several members of the Pseudomonas genus, among which the soil bacterium P. fluorescens Pf0-1. In this bacterium, the tspo gene is located in the vicinity of a putative hybrid histidine kinase-encoding gene. Since tspo has been involved in water stress related response in plants, we explored the effects of hyperosmolarity and temperature on P. fluorescens Pf0-1 tspo expression using a strategy based on lux-reporter fusions. We show that the two genes Pfl01_2810 and tspo are co-transcribed forming a transcription unit. The expression of this operon is growth phase-dependent and is increased in response to high concentrations of NaCl, sucrose and to a D-cycloserine treatment, which are conditions leading to activity of the major cell wall stress responsive extracytoplasmic sigma factor AlgU. Interestingly, the promoter region activity is strongly lowered in a P. aeruginosa algU mutant, suggesting that AlgU may be involved at least partly in the molecular mechanism leading to Pfl01_2810-tspo expression. In silico analysis of this promoter region failed to detect an AlgU consensus binding site; however, a putative binding site for the heat shock response RpoH sigma factor was detected. Accordingly, the promoter activity of the region containing this sequence is increased in response to high growth temperature and slightly lowered in a P. aeruginosa rpoH mutant strain. Taken together, our data suggest that P. fluorescens tspo gene may belong at least partly to the cell wall stress response. PMID:26441945

  17. Expression of the translocator protein (TSPO) from Pseudomonas fluorescens Pf0-1 requires the stress regulatory sigma factors AlgU and RpoH

    PubMed Central

    Leneveu-Jenvrin, Charlène; Bouffartigues, Emeline; Maillot, Olivier; Cornelis, Pierre; Feuilloley, Marc G. J.; Connil, Nathalie; Chevalier, Sylvie

    2015-01-01

    The translocator protein (TSPO), previously designated as peripheral-type benzodiazepine receptor, is an evolutionary conserved protein that is found in many Eukarya, Archae, and Bacteria, in which it plays several important functions including for example membrane biogenesis, signaling, and stress response. A tspo homolog gene has been identified in several members of the Pseudomonas genus, among which the soil bacterium P. fluorescens Pf0-1. In this bacterium, the tspo gene is located in the vicinity of a putative hybrid histidine kinase-encoding gene. Since tspo has been involved in water stress related response in plants, we explored the effects of hyperosmolarity and temperature on P. fluorescens Pf0-1 tspo expression using a strategy based on lux-reporter fusions. We show that the two genes Pfl01_2810 and tspo are co-transcribed forming a transcription unit. The expression of this operon is growth phase-dependent and is increased in response to high concentrations of NaCl, sucrose and to a D-cycloserine treatment, which are conditions leading to activity of the major cell wall stress responsive extracytoplasmic sigma factor AlgU. Interestingly, the promoter region activity is strongly lowered in a P. aeruginosa algU mutant, suggesting that AlgU may be involved at least partly in the molecular mechanism leading to Pfl01_2810-tspo expression. In silico analysis of this promoter region failed to detect an AlgU consensus binding site; however, a putative binding site for the heat shock response RpoH sigma factor was detected. Accordingly, the promoter activity of the region containing this sequence is increased in response to high growth temperature and slightly lowered in a P. aeruginosa rpoH mutant strain. Taken together, our data suggest that P. fluorescens tspo gene may belong at least partly to the cell wall stress response. PMID:26441945

  18. SIGffRid: A tool to search for sigma factor binding sites in bacterial genomes using comparative approach and biologically driven statistics

    PubMed Central

    Touzain, Fabrice; Schbath, Sophie; Debled-Rennesson, Isabelle; Aigle, Bertrand; Kucherov, Gregory; Leblond, Pierre

    2008-01-01

    Background Many programs have been developed to identify transcription factor binding sites. However, most of them are not able to infer two-word motifs with variable spacer lengths. This case is encountered for RNA polymerase Sigma (σ) Factor Binding Sites (SFBSs) usually composed of two boxes, called -35 and -10 in reference to the transcription initiation point. Our goal is to design an algorithm detecting SFBS by using combinational and statistical constraints deduced from biological observations. Results We describe a new approach to identify SFBSs by comparing two related bacterial genomes. The method, named SIGffRid (SIGma Factor binding sites Finder using R'MES to select Input Data), performs a simultaneous analysis of pairs of promoter regions of orthologous genes. SIGffRid uses a prior identification of over-represented patterns in whole genomes as selection criteria for potential -35 and -10 boxes. These patterns are then grouped using pairs of short seeds (of which one is possibly gapped), allowing a variable-length spacer between them. Next, the motifs are extended guided by statistical considerations, a feature that ensures a selection of motifs with statistically relevant properties. We applied our method to the pair of related bacterial genomes of Streptomyces coelicolor and Streptomyces avermitilis. Cross-check with the well-defined SFBSs of the SigR regulon in S. coelicolor is detailed, validating the algorithm. SFBSs for HrdB and BldN were also found; and the results suggested some new targets for these σ factors. In addition, consensus motifs for BldD and new SFBSs binding sites were defined, overlapping previously proposed consensuses. Relevant tests were carried out also on bacteria with moderate GC content (i.e. Escherichia coli/Salmonella typhimurium and Bacillus subtilis/Bacillus licheniformis pairs). Motifs of house-keeping σ factors were found as well as other SFBSs such as that of SigW in Bacillus strains. Conclusion We demonstrate

  19. Effect of hot-water extraction (HWE) severity on bleached pulp based biorefinery performance of eucalyptus during the HWE-Kraft-ECF bleaching process.

    PubMed

    Liu, Jing; Li, Meng; Luo, Xiaolin; Chen, Lihui; Huang, Liulian

    2015-04-01

    The effectiveness of a biorefinery based on an HWE-Kraft-ECF bleaching process and the end use of pulp was systematically evaluated. Using a P-factor of 198, nearly 30% of xylan-based sugars were recovered. The resulting pulp and paper properties were found to be comparable with the control. A maximum xylan-based sugar recovery of nearly 50% was achieved at a P-factor of 738. Although the strength of this P-factor induced handsheet was lower than that of the control by about 20%, the corresponding pulp was sufficient for dissolving pulp application. However, once the P-factor rose above 1189, hemicellulose sugars were significantly degraded into furans; pulp and paper properties were also deteriorated due to cellulose degradation, lignin deposition and condensation. Thus, considering the different end use of pulps, the performance of an HWE-based biorefinery could be balanced by its HWE severity. PMID:25647029

  20. Quality of life in patients with advanced gastric cancer: a randomized trial comparing docetaxel, cisplatin, 5-FU (TCF) with epirubicin, cisplatin, 5-FU (ECF)

    PubMed Central

    Sadighi, Sanambar; Mohagheghi, Mohammad Ali; Montazeri, Ali; Sadighi, Zahra

    2006-01-01

    Background Health related quality of life (HRQOL) is an important outcome after treatment for upper gastrointestinal carcinoma. This study aimed to compare HRQOL in patients with advanced gastric cancer (GC) receiving either a standard or an experimental treatment. Methods Seventy-one patients have been treated in Cancer Institute (Tehran, Iran) with docetaxel, cisplatin, 5 FU (TCF) or epirubicin, cisplatin, 5-FU (ECF) and were followed from Jan 2002 to Jan 2005. End points were response rate, HRQOL and survival. HRQOL was assessed using the EORCT QLQ-C30 at baseline and after the third cycle of chemotherapy. Results The baseline HRQOL scores were comparable between two groups. After treatment improvement was seen in a number of items and domains except for cognitive functioning, and diarrhoea. Pain decreased and physical functioning improved in both groups. However, only the TCF group showed statistically and clinically meaningful improvement in global QOL (P = 0.001). Surgical and pathologic response was better with TCF but there was no difference in survival rate between two groups. Conclusion Docetaxel based treatment (TCF) showed better palliation and improvement of global QOL as compared with epirubicin based treatment (ECF). However, it seems that regardless of treatment offered, effective chemotherapy was the most important factor affecting QOL in these patients. PMID:17147808

  1. Comparative Sigma Factor-mRNA Levels in Mycobacterium marinum under Stress Conditions and during Host Infection.

    PubMed

    Pettersson, B M Fredrik; Das, Sarbashis; Behra, Phani Rama Krishna; Jordan, Heather R; Ramesh, Malavika; Mallick, Amrita; Root, Kate M; Cheramie, Martin N; de la Cruz Melara, Irma; Small, Pamela L C; Dasgupta, Santanu; Ennis, Don G; Kirsebom, Leif A

    2015-01-01

    We have used RNASeq and qRT-PCR to study mRNA levels for all σ-factors in different Mycobacterium marinum strains under various growth and stress conditions. We also studied their levels in M. marinum from infected fish and mosquito larvae. The annotated σ-factors were expressed and transcripts varied in relation to growth and stress conditions. Some were highly abundant such as sigA, sigB, sigC, sigD, sigE and sigH while others were not. The σ-factor mRNA profiles were similar after heat stress, during infection of fish and mosquito larvae. The similarity also applies to some of the known heat shock genes such as the α-crystallin gene. Therefore, it seems probable that the physiological state of M. marinum is similar when exposed to these different conditions. Moreover, the mosquito larvae data suggest that this is the state that the fish encounter when infected, at least with respect to σ-factor mRNA levels. Comparative genomic analysis of σ-factor gene localizations in three M. marinum strains and Mycobacterium tuberculosis H37Rv revealed chromosomal rearrangements that changed the localization of especially sigA, sigB, sigD, sigE, sigF and sigJ after the divergence of these two species. This may explain the variation in species-specific expression upon exposure to different growth conditions. PMID:26445268

  2. Comparative Sigma Factor-mRNA Levels in Mycobacterium marinum under Stress Conditions and during Host Infection

    PubMed Central

    Pettersson, B. M. Fredrik; Das, Sarbashis; Behra, Phani Rama Krishna; Jordan, Heather R.; Ramesh, Malavika; Mallick, Amrita; Root, Kate M.; Cheramie, Martin N.; de la Cruz Melara, Irma; Small, Pamela L. C.; Dasgupta, Santanu; Ennis, Don G.; Kirsebom, Leif A.

    2015-01-01

    We have used RNASeq and qRT-PCR to study mRNA levels for all σ-factors in different Mycobacterium marinum strains under various growth and stress conditions. We also studied their levels in M. marinum from infected fish and mosquito larvae. The annotated σ-factors were expressed and transcripts varied in relation to growth and stress conditions. Some were highly abundant such as sigA, sigB, sigC, sigD, sigE and sigH while others were not. The σ-factor mRNA profiles were similar after heat stress, during infection of fish and mosquito larvae. The similarity also applies to some of the known heat shock genes such as the α-crystallin gene. Therefore, it seems probable that the physiological state of M. marinum is similar when exposed to these different conditions. Moreover, the mosquito larvae data suggest that this is the state that the fish encounter when infected, at least with respect to σ-factor mRNA levels. Comparative genomic analysis of σ-factor gene localizations in three M. marinum strains and Mycobacterium tuberculosis H37Rv revealed chromosomal rearrangements that changed the localization of especially sigA, sigB, sigD, sigE, sigF and sigJ after the divergence of these two species. This may explain the variation in species-specific expression upon exposure to different growth conditions. PMID:26445268

  3. The Extracytoplasmic Function Sigma Factor SigY Is Important for Efficient Maintenance of the Spβ Prophage That Encodes Sublancin in Bacillus subtilis

    PubMed Central

    Mendez, Rebecca; Gutierrez, Alba; Reyes, Jasmin

    2012-01-01

    Many strains of the soil bacterium Bacillus subtilis are capable of producing and being resistant to the antibiotic sublancin because they harbor the Spβ prophage. This 135 kb viral genome is integrated into the circular DNA chromosome of B. subtilis, and contains genes for the production of and resistance to sublancin. We investigated the role of SigY in sublancin production and resistance, finding that it is important for efficient maintenance of the Spβ prophage. We were unable to detect the prophage in mutants lacking SigY. Additionally, these mutants were no longer able to produce sublancin, were sensitive to killing by this factor, and displayed a delay in sporulation. Wild-type cells with normal SigY activity were found to partially lose the Spβ prophage during growth and early sporulation, suggesting a mechanism for the bistable outcome of sibling cells capable of killing and of being killed. The appropriate regulation of SigY appears to be essential for growth as evidenced by the inability to disrupt the gene for its putative antisigma. Our results confirm a role for SigY in antibiotic production and resistance, as has been found for other members of the extracytoplasmic function sigma factor family in B. subtilis, and shows that this role is achieved by affecting maintenance of the Spβ prophage. PMID:22400495

  4. The Staphylococcus aureus Alternative Sigma Factor ςB Controls the Environmental Stress Response but Not Starvation Survival or Pathogenicity in a Mouse Abscess Model

    PubMed Central

    Chan, Pan F.; Foster, Simon J.; Ingham, Eileen; Clements, Mark O.

    1998-01-01

    The role of ςB, an alternative sigma factor of Staphylococcus aureus, has been characterized in response to environmental stress, starvation-survival and recovery, and pathogenicity. ςB was mainly expressed during the stationary phase of growth and was repressed by 1 M sodium chloride. A sigB insertionally inactivated mutant was created. In stress resistance studies, ςB was shown to be involved in recovery from heat shock at 54°C and in acid and hydrogen peroxide resistance but not in resistance to ethanol or osmotic shock. Interestingly, S. aureus acquired increased acid resistance when preincubated at a sublethal pH 4 prior to exposure to a lethal pH 2. This acid-adaptive response resulting in tolerance was mediated via sigB. However, ςB was not vital for the starvation-survival or recovery mechanisms. ςB does not have a major role in the expression of the global regulator of virulence determinant biosynthesis, staphylococcal accessory regulator (sarA), the production of a number of representative virulence factors, and pathogenicity in a mouse subcutaneous abscess model. However, SarA upregulates sigB expression in a growth-phase-dependent manner. Thus, ςB expression is linked to the processes controlling virulence determinant production. The role of ςB as a major regulator of the stress response, but not of starvation-survival, is discussed. PMID:9829915

  5. Manage your human sigma.

    PubMed

    Fleming, John H; Coffman, Curt; Harter, James K

    2005-01-01

    If sales and service organizations are to improve, they must learn to measure and manage the quality of the employee-customer encounter. Quality improvement methodologies such as Six Sigma are extremely useful in manufacturing contexts, but they're less useful when it comes to human interactions. To address this problem, the authors have developed a quality improvement approach they refer to as Human Sigma. It weaves together a consistent method for assessing the employee-customer encounter and a disciplined process for managing and improving it. There are several core principles for measuring and managing the employee-customer encounter: It's important not to think like an economist or an engineer when assessing interactions because emotions inform both sides' judgments and behavior. The employee-customer encounter must be measured and managed locally, because there are enormous variations in quality at the work-group and individual levels. And to improve the quality of the employee-customer interaction, organizations must conduct both short-term, transactional interventions and long-term, transformational ones. Employee engagement and customer engagement are intimately connected--and, taken together, they have an outsized effect on financial performance. They therefore need to be managed holistically. That is, the responsibility for measuring and monitoring the health of employee-customer relationships must reside within a single organizational structure, with an executive champion who has the authority to initiate and manage change. Nevertheless, the local manager remains the single most important factor in local group performance. A local manager whose work group shows suboptimal performance should be encouraged to conduct interventions, such as targeted training, performance reviews, action learning, and individual coaching. PMID:16028821

  6. Roles of Group 2 Sigma Factors in Acclimation of the Cyanobacterium Synechocystis sp. PCC 6803 to Nitrogen Deficiency.

    PubMed

    Antal, Taras; Kurkela, Juha; Parikainen, Marjaana; Kårlund, Anna; Hakkila, Kaisa; Tyystjärvi, Esa; Tyystjärvi, Taina

    2016-06-01

    Acclimation of cyanobacteria to environmental conditions is mainly controlled at the transcriptional level, and σ factors of the RNA polymerase have a central role in this process. The model cyanobacterium Synechocystis sp. PCC 6803 has four non-essential group 2 σ factors (SigB, SigC, SigD and SigE) that regulate global metabolic responses to various adverse environmental conditions. Here we show that although none of the group 2 σ factors is essential for the major metabolic realignments induced by a short period of nitrogen starvation, the quadruple mutant without any group 2 σ factors and triple mutants missing both SigB and SigD grow slowly in BG-11 medium containing only 5% of the nitrate present in standard BG-11. These ΔsigBCDE, ΔsigBCD and ΔsigBDE strains lost PSII activity rapidly in low nitrogen and accumulated less glycogen than the control strain. An abnormally high glycogen content was detected in ΔsigBCE (SigD is active), while the carotenoid content became high in ΔsigCDE (SigB is active), indicating that SigB and SigD regulate the partitioning of carbon skeletons in low nitrogen. Long-term survival and recovery of the cells after nitrogen deficiency was strongly dependent on group 2 σ factors. The quadruple mutant and the ΔsigBDE strain (only SigC is active) recovered more slowly from nitrogen deficiency than the control strain, and ΔsigBCDE in particular lost viability during nitrogen starvation. Nitrogen deficiency-induced changes in the pigment content of the control strain recovered essentially in 1 d in nitrogen-replete medium, but little recovery occurred in ΔsigBCDE and ΔsigBDE. PMID:27095737

  7. Evaluation of early conception factor lateral flow test to determine nonpregnancy in dairy cattle.

    PubMed

    Ambrose, Divakar J; Radke, Brian; Pitney, Phyllis A; Goonewardene, Laksiri A

    2007-08-01

    The early conception factor (ECF) lateral flow test was evaluated for its ability to accurately determine nonpregnant status in dairy cattle. Results of 2 field trials involving 191 cows and 832 tests indicated the probability that a cow can be correctly diagnosed as nonpregnant by using the ECF test is only about 50%. Agreement of test results between milk and serum obtained from the same cow was 57.5%. The ECF test was not consistent in identifying nonpregnancy when the same cows were tested repeatedly over a period of 4 weeks. We conclude that the ECF lateral flow test does not accurately identify nonpregnancy in dairy cattle. PMID:17824326

  8. ECFS: A decentralized, distributed and fault-tolerant FUSE filesystem for the LHCb online farm

    NASA Astrophysics Data System (ADS)

    Rybczynski, Tomasz; Bonaccorsi, Enrico; Neufeld, Niko

    2014-06-01

    The LHCb experiment records millions of proton collisions every second, but only a fraction of them are useful for LHCb physics. In order to filter out the "bad events" a large farm of x86-servers (~2000 nodes) has been put in place. These servers boot from and run from NFS, however they use their local disk to temporarily store data, which cannot be processed in real-time ("data-deferring"). These events are subsequently processed, when there are no live-data coming in. The effective CPU power is thus greatly increased. This gain in CPU power depends critically on the availability of the local disks. For cost and power-reasons, mirroring (RAID-1) is not used, leading to a lot of operational headache with failing disks and disk-errors or server failures induced by faulty disks. To mitigate these problems and increase the reliability of the LHCb farm, while at same time keeping cost and power-consumption low, an extensive research and study of existing highly available and distributed file systems has been done. While many distributed file systems are providing reliability by "file replication", none of the evaluated ones supports erasure algorithms. A decentralised, distributed and fault-tolerant "write once read many" file system has been designed and implemented as a proof of concept providing fault tolerance without using expensive - in terms of disk space - file replication techniques and providing a unique namespace as a main goals. This paper describes the design and the implementation of the Erasure Codes File System (ECFS) and presents the specialised FUSE interface for Linux. Depending on the encoding algorithm ECFS will use a certain number of target directories as a backend to store the segments that compose the encoded data. When target directories are mounted via nfs/autofs - ECFS will act as a file-system over network/block-level raid over multiple servers.

  9. Determinants of redox sensitivity in RsrA, a zinc-containing anti-sigma factor for regulating thiol oxidative stress response

    PubMed Central

    Jung, Yong-Gyun; Cho, Yoo-Bok; Kim, Min-Sik; Yoo, Ji-Sun; Hong, Seok-Hyeon; Roe, Jung-Hye

    2011-01-01

    Various environmental oxidative stresses are sensed by redox-sensitive regulators through cysteine thiol oxidation or modification. A few zinc-containing anti-sigma (ZAS) factors in actinomycetes have been reported to respond sensitively to thiol oxidation, among which RsrA from Streptomyces coelicolor is best characterized. It forms disulfide bonds upon oxidation and releases bound SigR to activate thiol oxidative stress response genes. Even though numerous ZAS proteins exist in bacteria, features that confer redox sensitivity to a subset of these have been uncharacterized. In this study, we identified seven additional redox-sensitive ZAS factors from actinomycetes. Comparison with redox-insensitive ZAS revealed characteristic sequence patterns. Domain swapping demonstrated the significance of the region K33FEHH37FEEC41SPC44LEK47 that encompass the conserved HX3CX2C (HCC) motif. Mutational effect of each residue on diamide responsive induction of SigR target genes in vivo demonstrated that several residues, especially those that flank two cysteines (E39, E40, L45, E46), contribute to redox sensitivity. These residues are well conserved among redox-sensitive ZAS factors, and hence are proposed as redox-determinants in sensitive ZAS. H37A, C41A, C44A and F38A mutations, in contrast, compromised SigR-binding activity significantly, apparently affecting structural integrity of RsrA. The residue pattern around HCC motif could therefore serve as an indicator to predict redox-sensitive ZAS factors from sequence information. PMID:21685450

  10. Genotoxicity and toxicity evaluations of ECF cellulose bleaching effluents using the Allium cepa L. test.

    PubMed

    Roa, O; Yeber, M C; Venegas, W

    2012-08-01

    Toxicity and genotoxicity tests were performed on root cells of Allium cepa in order to evaluate wastewater quality following an ECF cellulose bleaching process. The results revealed a toxic effect of the effluent, with inhibition of meristem growth and generally lower values of metaphase, anaphase and telophase indices at pH 10.5 than pH 7 for all effluent concentrations. The genotoxicity effect was different from the toxic effect given that the micronucleus and the chromosomal aberration tests in anaphase-telophase cells were low over all ranges of the studied effluent concentrations. PMID:22990817

  11. The nuclear-encoded sigma factor SIG4 directly activates transcription of chloroplast psbA and ycf17 genes in the unicellular red alga Cyanidioschyzon merolae.

    PubMed

    Fujii, Gaku; Imamura, Sousuke; Era, Atsuko; Miyagishima, Shin-ya; Hanaoka, Mitsumasa; Tanaka, Kan

    2015-05-01

    The plant organelle chloroplast originated from the endosymbiosis of a cyanobacterial-like photosynthetic bacterium, and still retains its own genome derived from this ancestor. We have been focusing on a unicellular red alga, Cyanidioschyzon merolae, as a model photosynthetic eukaryote. In this study, we analyzed the transcriptional specificity of SIG4, which is one of four nuclear-encoded chloroplast RNA polymerase sigma factors in this alga. Accumulation of the SIG4 protein was observed in response to nitrogen depletion or high light conditions. By comparing the chloroplast transcriptomes under nitrogen depletion and SIG4-overexpressing conditions, we identified several candidate genes as SIG4 targets. Together with the results of chromatin immunoprecipitation analysis, the promoters of the psbA (encoding the D1 protein of the photosystem II reaction center) and ycf17 (encoding a protein of the early light-inducible protein family) genes were shown to be direct activation targets. The phycobilisome (PBS) CpcB protein was decreased by SIG4 overexpression, which suggests the negative involvement of SIG4 in PBS accumulation. PMID:25883111

  12. Resilience in the Face of Uncertainty: Sigma Factor B Fine-Tunes Gene Expression To Support Homeostasis in Gram-Positive Bacteria.

    PubMed

    Guldimann, Claudia; Boor, Kathryn J; Wiedmann, Martin; Guariglia-Oropeza, Veronica

    2016-08-01

    Gram-positive bacteria are ubiquitous and diverse microorganisms that can survive and sometimes even thrive in continuously changing environments. The key to such resilience is the ability of members of a population to respond and adjust to dynamic conditions in the environment. In bacteria, such responses and adjustments are mediated, at least in part, through appropriate changes in the bacterial transcriptome in response to the conditions encountered. Resilience is important for bacterial survival in diverse, complex, and rapidly changing environments and requires coordinated networks that integrate individual, mechanistic responses to environmental cues to enable overall metabolic homeostasis. In many Gram-positive bacteria, a key transcriptional regulator of the response to changing environmental conditions is the alternative sigma factor σ(B) σ(B) has been characterized in a subset of Gram-positive bacteria, including the genera Bacillus, Listeria, and Staphylococcus Recent insight from next-generation-sequencing results indicates that σ(B)-dependent regulation of gene expression contributes to resilience, i.e., the coordination of complex networks responsive to environmental changes. This review explores contributions of σ(B) to resilience in Bacillus, Listeria, and Staphylococcus and illustrates recently described regulatory functions of σ(B). PMID:27208112

  13. The anti-sigma factor TcdC modulates hypervirulence in an epidemic BI/NAP1/027 clinical isolate of Clostridium difficile.

    PubMed

    Carter, Glen P; Douce, Gillian R; Govind, Revathi; Howarth, Pauline M; Mackin, Kate E; Spencer, Janice; Buckley, Anthony M; Antunes, Ana; Kotsanas, Despina; Jenkin, Grant A; Dupuy, Bruno; Rood, Julian I; Lyras, Dena

    2011-10-01

    Nosocomial infections are increasingly being recognised as a major patient safety issue. The modern hospital environment and associated health care practices have provided a niche for the rapid evolution of microbial pathogens that are well adapted to surviving and proliferating in this setting, after which they can infect susceptible patients. This is clearly the case for bacterial pathogens such as Methicillin Resistant Staphylococcus aureus (MRSA) and Vancomycin Resistant Enterococcus (VRE) species, both of which have acquired resistance to antimicrobial agents as well as enhanced survival and virulence properties that present serious therapeutic dilemmas for treating physicians. It has recently become apparent that the spore-forming bacterium Clostridium difficile also falls within this category. Since 2000, there has been a striking increase in C. difficile nosocomial infections worldwide, predominantly due to the emergence of epidemic or hypervirulent isolates that appear to possess extended antibiotic resistance and virulence properties. Various hypotheses have been proposed for the emergence of these strains, and for their persistence and increased virulence, but supportive experimental data are lacking. Here we describe a genetic approach using isogenic strains to identify a factor linked to the development of hypervirulence in C. difficile. This study provides evidence that a naturally occurring mutation in a negative regulator of toxin production, the anti-sigma factor TcdC, is an important factor in the development of hypervirulence in epidemic C. difficile isolates, presumably because the mutation leads to significantly increased toxin production, a contentious hypothesis until now. These results have important implications for C. difficile pathogenesis and virulence since they suggest that strains carrying a similar mutation have the inherent potential to develop a hypervirulent phenotype. PMID:22022270

  14. Three Good Reasons for Celebrating at the ESO/ST-ECF Science Archive Facility

    NASA Astrophysics Data System (ADS)

    2000-12-01

    Great Demand for Data from New "Virtual Observatory" Summary Due to a happy coincidence, the ESO/ST-ECF Science Archive Facility is celebrating three different milestones at the same time: * its 10th anniversary since the establishment in 1991 * the 10,000th request for data , and * the signing-up of active user number 2000 . This Archive contains over 8 Terabytes (1 Terabyte = 1 million million bytes) of valuable observational data from the NASA/ESA Hubble Space Telescope (HST), the ESO Very Large Telescope (VLT) and other ESO telescopes . Its success paves the way for the establishment of "Virtual Observatories" from which first-class data can be obtained by astronomers all over the world. This greatly enhances the opportunities for more (young) scientists to participate in front-line research. PR Photo 34/00 : Front-page of a new brochure, describing the ESO/ST-ECF Science Archive Facility. Just 10 years ago, on the 1st of January 1991, the ESO/ST-ECF (European Southern Observatory/Space Telescope-European Coordinating Facility) Science Archive Facility opened. It has since served the astronomical community with gigabyte after gigabyte of high-quality astronomical data from some of the world's leading telescopes. The Archive, which is located in Garching, just outside Munich (Germany), contains data from the 2.4-m NASA/ESA Hubble Space Telescope , as well as from several ESO telescopes: the four 8.2-m Unit Telescopes of the Very Large Telescope (VLT) at the Paranal Observatory , and the 3.5-m New Technology Telescope (NTT) , the 3.6-m telescope and the MPG/ESO 2.2-m telescope at La Silla. The Archive is a continuously developing project - in terms of amounts of data stored, the number of users and in particular because of the current dramatic development of innovative techniques for data handling and storage. In the year 2000 more than 2 Terabytes (2000 Gigabytes) of data were distributed to users worldwide. The archiving of VLT data has been described in ESO PR

  15. The Anti-sigma Factor RsiV Is a Bacterial Receptor for Lysozyme: Co-crystal Structure Determination and Demonstration That Binding of Lysozyme to RsiV Is Required for σV Activation.

    PubMed

    Hastie, Jessica L; Williams, Kyle B; Bohr, Lindsey L; Houtman, Jon C; Gakhar, Lokesh; Ellermeier, Craig D

    2016-09-01

    σ factors provide RNA polymerase with promoter specificity in bacteria. Some σ factors require activation in order to interact with RNA polymerase and transcribe target genes. The Extra-Cytoplasmic Function (ECF) σ factor, σV, is encoded by several Gram-positive bacteria and is specifically activated by lysozyme. This activation requires the proteolytic destruction of the anti-σ factor RsiV via a process of regulated intramembrane proteolysis (RIP). In many cases proteases that cleave at site-1 are thought to directly sense a signal and initiate the RIP process. We previously suggested binding of lysozyme to RsiV initiated the proteolytic destruction of RsiV and activation of σV. Here we determined the X-ray crystal structure of the RsiV-lysozyme complex at 2.3 Å which revealed that RsiV and lysozyme make extensive contacts. We constructed RsiV mutants with altered abilities to bind lysozyme. We find that mutants that are unable to bind lysozyme block site-1 cleavage of RsiV and σV activation in response to lysozyme. Taken together these data demonstrate that RsiV is a receptor for lysozyme and binding of RsiV to lysozyme is required for σV activation. In addition, the co-structure revealed that RsiV binds to the lysozyme active site pocket. We provide evidence that in addition to acting as a sensor for the presence of lysozyme, RsiV also inhibits lysozyme activity. Thus we have demonstrated that RsiV is a protein with multiple functions. RsiV inhibits σV activity in the absence of lysozyme, RsiV binds lysozyme triggering σV activation and RsiV inhibits the enzymatic activity of lysozyme. PMID:27602573

  16. Alternative Sigma Factors SigF, SigE, and SigG Are Essential for Sporulation in Clostridium botulinum ATCC 3502

    PubMed Central

    Kirk, David G.; Zhang, Zhen; Korkeala, Hannu

    2014-01-01

    Clostridium botulinum produces heat-resistant endospores that may germinate and outgrow into neurotoxic cultures in foods. Sporulation is regulated by the transcription factor Spo0A and the alternative sigma factors SigF, SigE, SigG, and SigK in most spore formers studied to date. We constructed mutants of sigF, sigE, and sigG in C. botulinum ATCC 3502 and used quantitative reverse transcriptase PCR and electron microscopy to assess their expression of the sporulation pathway on transcriptional and morphological levels. In all three mutants the expression of spo0A was disrupted. The sigF and sigE mutants failed to induce sigG and sigK beyond exponential-phase levels and halted sporulation during asymmetric cell division. In the sigG mutant, peak transcription of sigE was delayed and sigK levels remained lower than that in the parent strain. The sigG mutant forespore was engulfed by the mother cell and possessed a spore coat but no peptidoglycan cortex. The findings suggest that SigF and SigE of C. botulinum ATCC 3502 are essential for early sporulation and late-stage induction of sigK, whereas SigG is essential for spore cortex formation but not for coat formation, as opposed to previous observations in B. subtilis sigG mutants. Our findings add to a growing body of evidence that regulation of sporulation in C. botulinum ATCC 3502, and among the clostridia, differs from the B. subtilis model. PMID:24928875

  17. Phosphotransferase system-dependent extracellular growth of listeria monocytogenes is regulated by alternative sigma factors σL and σH.

    PubMed

    Wang, Siyun; Orsi, Renato H; Tang, Silin; Zhang, Wei; Wiedmann, Martin; Boor, Kathryn J

    2014-12-01

    Alternative sigma (σ) factors and phosphotransferase systems (PTSs) play pivotal roles in the environmental adaptation and virulence of Listeria monocytogenes. The growth of the L. monocytogenes parent strain 10403S and 15 isogenic alternative σ factor mutants was assessed in defined minimal medium (DM) with PTS-dependent or non-PTS-dependent carbon sources at 25°C or 37°C. Overall, our results suggested that the regulatory effect of alternative σ factors on the growth of L. monocytogenes is dependent on the temperature and the carbon source. One-way analysis of variance (one-way ANOVA) showed that the factor "strain" had a significant effect on the maximum growth rate (μmax), lag phase duration (λ), and maximum optical density (ODmax) in PTS-dependent carbon sources (P < 0.05) but not in a non-PTS-dependent carbon source. Also, the ODmax was not affected by strain for any of the three PTS-dependent carbon sources at 25°C but was affected by strain at 37°C. Monitoring by quantitative real-time PCR (qRT-PCR) showed that transcript levels for lmo0027, a glucose-glucoside PTS permease (PTS(Glc)-1)-encoding gene, were higher in the absence of σ(L), and lower in the absence of σ(H), than in the parent strain. Our data thus indicate that σ(L) negatively regulates lmo0027 and that the increased μmax observed for the ΔsigL strain in DM with glucose may be associated with increased expression of PTS(Glc)-1 encoded by lmo0027. Our findings suggest that σ(H) and σ(L) mediate the PTS-dependent growth of L. monocytogenes through complex transcriptional regulations and fine-tuning of the expression of specific pts genes, including lmo0027. Our findings also reveal a more important and complex role of alternative σ factors in the regulation of growth in different sugar sources than previously assumed. PMID:25281379

  18. Supersymmetric sigma models

    SciTech Connect

    Bagger, J.A.

    1984-09-01

    We begin to construct the most general supersymmetric Lagrangians in one, two and four dimensions. We find that the matter couplings have a natural interpretation in the language of the nonlinear sigma model.

  19. MexCD-OprJ multidrug efflux system of Pseudomonas aeruginosa: involvement in chlorhexidine resistance and induction by membrane-damaging agents dependent upon the AlgU stress response sigma factor.

    PubMed

    Fraud, Sebastien; Campigotto, Aaron J; Chen, Zhilin; Poole, Keith

    2008-12-01

    The biocide chlorhexidine (CHX) as well as additional membrane-active agents were shown to induce expression of the mexCD-oprJ multidrug efflux operon, dependent upon the AlgU stress response sigma factor. Hyperexpression of this efflux system in nfxB mutants was also substantially AlgU dependent. CHX resistance correlated with efflux gene expression in various mutants, consistent with MexCD-OprJ being a determinant of CHX resistance. PMID:18838593

  20. microRNA (miRNA) speciation in Alzheimer's disease (AD) cerebrospinal fluid (CSF) and extracellular fluid (ECF).

    PubMed

    Alexandrov, Peter N; Dua, Prerna; Hill, James M; Bhattacharjee, Surjyadipta; Zhao, Yuhai; Lukiw, Walter J

    2012-01-01

    Human cerebrospinal fluid (CSF), produced by the choroid plexus and secreted into the brain ventricles and subarachnoid space, plays critical roles in intra-cerebral transport and the biophysical and immune protection of the brain. CSF composition provides valuable insight into soluble pathogenic bio-markers that may be diagnostic for brain disease. In these experiments we analyzed amyloid beta (Aβ) peptide and micro RNA (miRNA) abundance in CSF and in short post-mortem interval (PMI <2.1 hr) brain tissue-derived extracellular fluid (ECF) from Alzheimer's disease (AD) and age-matched control neocortex. There was a trend for decreased abundance of Aβ42 in the CSF and ECF in AD but it did not reach statistical significance (mean age ~72 yr; N=12; p~0.06, ANOVA). The most abundant nucleic acids in AD CSF and ECF were miRNAs, and their speciation and inducibility were studied further. Fluorescent miRNA-array-based analysis indicated significant increases in miRNA-9, miRNA-125b, miRNA-146a, miRNA-155 in AD CSF and ECF (N=12; p<0.01, ANOVA). Primary human neuronal-glial (HNG) cell co-cultures stressed with AD-derived ECF also displayed an up-regulation of these miRNAs, an effect that was quenched using the anti-NF-кB agents caffeic acid phenethyl ester (CAPE) or 1-fluoro-2-[2-(4-methoxy-phenyl)-ethenyl]-benzene (CAY10512). Increases in miRNAs were confirmed independently using a highly sensitive LED-Northern dot-blot assay. Several of these NF-кB-sensitive miRNAs are known to be up-regulated in AD brain, and associate with the progressive spreading of inflammatory neurodegeneration. The results indicate that miRNA-9, miRNA-125b, miRNA-146a and miRNA-155 are CSF- and ECF-abundant, NF-кB-sensitive pro-inflammatory miRNAs, and their enrichment in circulating CSF and ECF suggest that they may be involved in the modulation or proliferation of miRNA-triggered pathogenic signaling throughout the brain and central nervous system (CNS). PMID:23301201

  1. Two stress sensor proteins for the expression of sigmaE regulon: DegS and RseB.

    PubMed

    Kim, Dong Young

    2015-05-01

    In E. coli, sigmaE-dependent transcription is controlled by regulated-proteolysis of RseA. RseA, which holds sigmaE as an anti-sigma factor, is sequentially digested by DegS, RseP and cytoplasmic proteases to liberate sigmaE in response to dysfunction in outer-membrane biogenesis. Additionally, the sequential proteolysis is regulated by RseB binding to RseA (Fig. 1A). Direct interaction between RseA and RseB inhibits RseA-cleavage by DegS. Both proteolytic activation of DegS and binding disruption of RseB are thus required to initiate sigmaE-stress response. For the induction of sigmaEstress response, DegS and RseB recognize the states of OMP and LPS for outer-membrane biogenesis. DegS is activated by binding of unfolded OMPs and RseB binding to RseA is antagonized by LPS accumulated in periplasm. In this regard, DegS and RseB are proposed to be stress sensor proteins for sigmaE signal transduction. Interestingly, biogenesis of OMP and LPS appears to cross-talk with each other, indicating that dysfunction of either OMP or LPS can initiate RseA proteolysis. This review aims to briefly introduce two stress sensor proteins, DegS and RseB, which regulate sigmaEdependent transcription. PMID:25935301

  2. Negative regulation of Germination-Arrest Factor (GAF) production in Pseudomonas fluorescens WH6 by a putative extracytoplasmic function sigma factor

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pseudomonas fluorescens WH6 secretes a Germination-Arrest Factor (GAF) that we have previously identified as 4-formylaminooxyvinylglycine. GAF irreversibly inhibits germination of the seeds of numerous grassy weed species and selectively inhibits growth of the bacterial plant pathogen Erwinia amylo...

  3. Induction of Fibronectin Adhesins in Quinolone-Resistant Staphylococcus aureus by Subinhibitory Levels of Ciprofloxacin or by Sigma B Transcription Factor Activity Is Mediated by Two Separate Pathways

    PubMed Central

    Li, Dongmei; Renzoni, Adriana; Estoppey, Tristan; Bisognano, Carmelo; Francois, Patrice; Kelley, William L.; Lew, Daniel P.; Schrenzel, Jacques; Vaudaux, Pierre

    2005-01-01

    We recently reported on the involvement of a RecA-LexA-dependent pathway in the ciprofloxacin-triggered upregulation of fibronectin-binding proteins (FnBPs) by fluoroquinolone-resistant Staphylococcus aureus. The potential additional contribution of the transcription factor sigma B (SigB) to the ciprofloxacin-triggered upregulation of FnBPs was studied in isogenic mutants of fluoroquinolone-resistant strain RA1 (a topoisomerase IV gyrase double mutant of S. aureus NCTC strain 8325), which exhibited widely different levels of SigB activity, as assessed by quantitative reverse transcription-PCR of their respective sigB and SigB-dependent asp23 transcript levels. These mutants were Tn551 insertion sigB strain TE1 and rsbU+ complemented strain TE2, which exhibited a wild-type SigB operon. Levels of FnBP surface display and fibronectin-mediated adhesion were lower in sigB mutant TE1 or higher in the rsbU+-restored strain TE2 compared to their sigB+ but rsbU parent, strain RA1, exhibiting low levels of SigB activity. Steady-state fnbA and fnbB transcripts levels were similar in strains TE1 and RA1 but increased by 4- and 12-fold, respectively, in strain TE2 compared to those in strain RA1. In contrast, fibronectin-mediated adhesion of strains TE1, RA1, and TE2 was similarly enhanced by growth in the presence of one-eighth the MIC of ciprofloxacin, which led to a significantly higher increase in their fnbB transcript levels compared to the increase in their fnbA transcript levels. Increased SigB levels led to a significant reduction in agr RNAIII; in contrast, it led to a slight increase in sarA transcript levels. In conclusion, upregulation of FnBPs by increased SigB levels and ciprofloxacin exposure in fluoroquinolone-resistant S. aureus occurs via independent pathways whose concerted actions may significantly promote bacterial adhesion and colonization. PMID:15728884

  4. Structural insight in the toppling mechanism of an energy-coupling factor transporter

    PubMed Central

    Swier, Lotteke J. Y. M.; Guskov, Albert; Slotboom, Dirk J.

    2016-01-01

    Energy-coupling factor (ECF) transporters mediate uptake of micronutrients in prokaryotes. The transporters consist of an S-component that binds the transported substrate and an ECF module (EcfAA′T) that binds and hydrolyses ATP. The mechanism of transport is poorly understood but presumably involves an unusual step in which the membrane-embedded S-component topples over to carry the substrate across the membrane. In many ECF transporters, the S-component dissociates from the ECF module after transport. Subsequently, substrate-bound S-components out-compete the empty proteins for re-binding to the ECF module in a new round of transport. Here we present crystal structures of the folate-specific transporter ECF–FolT from Lactobacillus delbrueckii. Interaction of the ECF module with FolT stabilizes the toppled state, and simultaneously destroys the high-affinity folate-binding site, allowing substrate release into the cytosol. We hypothesize that differences in the kinetics of toppling can explain how substrate-loaded FolT out-competes apo-FolT for association with the ECF module. PMID:27026363

  5. Study ofe+e- to Lambda anti-Lambda, Lambda anti-Sigma^0,Sigma^0 anti-Sigma^0 using Initial State Radiation with BaBar

    SciTech Connect

    Aubert, B.

    2007-09-14

    We study the e+e- --> Lambda anti-Lambda gamma, Lambda anti-Sigma0 gamma, Sigma0 anti-Sigma0 gamma processes using 230 fb-1 of integrated luminosity collected by the BaBar detector at e+e- center-of-mass energy of 10.58 GeV. From the analysis of the baryon-antibaryon mass spectra the cross sections for e+e- --> Lambda anti-Lambda, Lambda anti-Sigma0, Sigma0 anti-Sigma0 are measured in the dibaryon mass range from threshold up to 3 GeV/c{sup 2}. The ratio of electric and magnetic form factors, |G{sub E}/G{sub M}|, is measured for e+e- --> Lambda anti-Lambda, and limits on the relative phase between Lambda form factors are obtained. We also measure the J/psi --> Lambda anti-Lambda, Sigma0 anti-Sigma0 and psi(2S) --> Lambda anti-Lambda branching fractions.

  6. The Architects of Modern Physics & Sigma Pi Sigma Heritage

    NASA Astrophysics Data System (ADS)

    White, Gary

    2004-10-01

    While the tools of modern physics were being honed throughout the last century, physicist Marsh W. White (no relation) served as the installation officer for over 200 chapters of the physics honor society, Sigma Pi Sigma. Years earlier, though, his 1926 thesis ``The Energy of High Velocity Electrons'' served as a direct test of one of Einstein's most radical 1905 ideas. The ``red books'' of Sigma Pi Sigma, into which all inductees pen their names, include some of the most talented quantum mechanics of the 20th century, such as Edward Teller and George Gamow. In this talk, I will review these and other links between Sigma Pi Sigma and some of the architects of modern physics.

  7. An esterase gene from Lactobacillus casei cotranscribed with genes encoding a phosphoenolpyruvate:sugar phosphotransferase system and regulated by a LevR-like activator and sigma54 factor.

    PubMed

    Yebra, María J; Viana, Rosa; Monedero, Vicente; Deutscher, Josef; Pérez-Martínez, Gaspar

    2004-01-01

    A new esterase-encoding gene was found in the draft genome sequence of Lactobacillus casei BL23 (CECT5275). It is located in an operon together with genes encoding the EIIA, EIIB, EIIC, and EIID proteins of a mannose class phosphoenolpyruvate:sugar phosphotransferase system. After overproduction in Escherichia coli and purification, the esterase could hydrolyze acetyl sugars, hence the operon was named esu for esterase-sugar uptake genes. Upstream of the genes encoding the EII components (esuABCD) and the esterase (esuE), two genes transcribed in the opposite sense were found which encode a Bacillus subtilis LevR-like transcriptional activator (esuR) and a sigma54-like transcriptional factor (rpoN). As compared with the wild-type strain, elevated fructose phosphorylation was detected in L. casei mutants constitutively expressing the esu operon. However, none of the many sugars tested could induce the esu operon. The fact that EsuE exhibits esterase activity on acetyl sugars suggests that this operon could be involved in the uptake and metabolism of esterified sugars. Expression of the esu operon is similar to that of the B. subtilis lev operon: it contains a -12,-24 consensus promoter typical of sigma54-regulated genes, and EsuR and RpoN are essential for its transcription which is negatively regulated by EIIB(Esu). The esuABCDE transcription unit represents the first sigma54-regulated operon in lactobacilli. Furthermore, replacement of His852 in the phosphoenolpyruvate:sugar phosphotransferase system regulation domain II of EsuR with Ala indicated that the transcription activator function of EsuR is inhibited by EIIB(Esu)-mediated phosphorylation at His852. PMID:15925903

  8. Regulation of sigma S degradation in Salmonella enterica var typhimurium: in vivo interactions between sigma S, the response regulator MviA(RssB) and ClpX.

    PubMed

    Moreno, M; Audia, J P; Bearson, S M; Webb, C; Foster, J W

    2000-04-01

    The alternate sigma factor sigmaS plays an important role in the survival of Salmonella typhimurium following sudden encounters with a variety of stress conditions. The level of sigmaS is very low in rapidly growing cells but dramatically increases as those cells encounter environmental stress or enter into stationary phase. This increase is due in large measure to the stabilization of sigmaS protein against degradation by the ClpXP protease. The MviA protein, also known as RssB or SprE in Escherichia coli, is a putative member of a two component signal transduction system that plays a central role in facilitating sigmaS degradation by ClpXP. In contrast to most two-component systems, MviA does not appear to regulate gene expression but is believed to interact directly with sigmaS and somehow facilitate degradation. We now provide evidence that MviA(RssB) directly interacts both with sigmaS and ClpX in vivo, presumably enabling presentation of sigmaS to the ClpP protease. Interactions were demonstrated using a bacterial two-hybrid system in which sigmaS, MviA, and ClpX were fused to separate moieties of Bordetella pertussis CyaA (adenylate cyclase). Paired hybrid plasmids containing Cya'-MviA/RpoS-'Cya or Cya'-MviA/ClpX-'Cya successfully reconstituted adenylate cyclase activity in both S. typhimurium and E. coli. However, no direct interactions were detected between ClpX and RpoS. A second series of experiments has indicated that the interaction between MviA and sigmaS requires the N-terminus but not the C-terminus of MviA. Cellular levels of MviA appear to be very low in the cell based on lacZ fusion, Western blot and Northern blot analyses suggesting a catalytic role for MviA in sigmaS degradation. Mutagenesis of MviA residue D58, a canonical residue subject to phosphorylation in many two-component systems, decreased the ability of MviA to facilitate sigmaS turnover in vivo confirming that phosphorylation of MviA increases MviA activity. PMID:10939250

  9. Identification of a putative alternate sigma factor and characterization of a multicomponent regulatory cascade controlling the expression of Pseudomonas syringae pv. syringae Pss61 hrp and hrmA genes.

    PubMed Central

    Xiao, Y; Heu, S; Yi, J; Lu, Y; Hutcheson, S W

    1994-01-01

    The Pseudomonas syringae hrp and hrmA genes controlling pathogenicity and elicitation of the hypersensitive response and the avr genes controlling host range have been shown previously to be regulated by carbon, nitrogen, pH, osmolarity, and hypothetical plant factors. In P. syringae pv. syringae Pss61, inactivation of hrp complementation groups II and XIII reduced expression of a plasmid-borne hrmA'-lacZ fusion. The hrp regions II and XIII were cloned on separate plasmids and shown to enhance the activity of the hrmA promoter in Escherichia coli MC4100 transformants at least 100-fold. The nucleotide sequence of region XIII revealed two open reading frames (hrpR and hrpS) whose deduced products share homology with P. syringae pv. phaseolicola NPS3121 HrpS and are both related to the NtrC family of two-component signal transduction systems. HrpR and HrpS differ from most members of the protein family by lacking an amino-terminal domain which modulates the regulatory activity. A single open reading frame, hrpL, whose product shares homology with AlgU, a putative alternate sigma factor of P. aeruginosa, as well as with the related alternate sigma factors was identified within region II. Key domains are partially conserved. Inactivation of hrpS in Pss61 repressed expression of a plasmid-borne hrpL'-lacZ fusion carried by pYXPL1R, and transformation of MC4100(pYXPL1R) with a plasmid carrying hrpRS increased hrpL promoter activity at least 200-fold. Neither hrpS nor hrpR, when cloned on separate plasmids, activated the hrpL promoter activity individually. The expression of hrpL when directed by a lac promoter was sufficient to express a set of plasmid-borne hrmA'-, hrpJ'-, and hrpZ'-lacZ fusions independently of other hrp genes. The results indicate that hrpRS and hrpL are part of a regulatory cascade in which HrpR and HrpS activate expression of hrpL and HrpL, a putative sigma factor, induces expression of HrpL-responsive genes. Images PMID:8106313

  10. Expression of the chaplin and rodlin hydrophobic sheath proteins in Streptomyces venezuelae is controlled by σ(BldN) and a cognate anti-sigma factor, RsbN.

    PubMed

    Bibb, Maureen J; Domonkos, Agota; Chandra, Govind; Buttner, Mark J

    2012-06-01

    The chaplin and rodlin proteins together constitute the major components of the hydrophobic sheath that coats the aerial hyphae and spores in Streptomyces, and mutants lacking the chaplins are unable to erect aerial hyphae and differentiate on minimal media. We have gained insight into the developmental regulation of the chaplin (chp) and rodlin (rdl) genes by exploiting a new model species, Streptomyces venezuelae, which sporulates in liquid culture. Using microarrays, the chaplin and rodlin genes were found to be highly induced during submerged sporulation in a bldN-dependent manner. Using σ(BldN) ChIP-chip, we show that this dependence arises because the chaplin and rodlin genes are direct biochemical targets of σ(BldN) . sven3186 (here named rsbN for regulator of sigma BldN), the gene lying immediately downstream of bldN, was also identified as a target of σ(BldN) . Disruption of rsbN causes precocious sporulation and biochemical experiments demonstrate that RsbN functions as a σ(BldN) -specific anti-sigma factor. PMID:22582857

  11. Genetic evidence for interaction of sigma E with the spoIIID promoter in Bacillus subtilis.

    PubMed Central

    Tatti, K M; Jones, C H; Moran, C P

    1991-01-01

    During sporulation in Bacillus subtilis, new RNA polymerase sigma factors are produced. These sigma factors direct the transcription of genes that are required for this cellular differentiation. In order to determine the role of each sigma factor in this process, it is necessary to know which promoters are recognized by each sigma factor. The spoIIID gene product plays an important role in the establishment of mother cell-specific gene expression during sporulation. We found that substitution of an alanine at position 124 of the sporulation-specific sigma factor sigma E suppressed the effect of a single-base-pair transition at position -13 of the spoIIID promoter. This alanine substitution in sigma E did not suppress the effect of a transversion at position -12 of the spoIIID promoter. The allele specificity of the interaction between sigma E and the spoIIID promoter is strong evidence that sigma E directs transcription from the spoIIID promoter during sporulation. Position 124 in sigma E is located within a region that is highly conserved among the regions in other sigma factors that probably interact with the -10 regions of their cognate promoters. Images FIG. 1 PMID:1744038

  12. Observation of the Heavy Baryons Sigma b and Sigma b*.

    PubMed

    Aaltonen, T; Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Behari, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carillo, S; Carlsmith, D; Carosi, R; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Cilijak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; DaRonco, S; Datta, M; D'Auria, S; Davies, T; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; De Lorenzo, G; Dell'Orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Dörr, C; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Forrest, R; Forrester, S; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jeon, E J; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kraan, A C; Kraus, J; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kulkarni, N P; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis, A; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moon, C S; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Tesarek, R J; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tsuno, S; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vazquez, F; Velev, G; Vellidis, C; Veramendi, G; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

    2007-11-16

    We report an observation of new bottom baryons produced in pp collisions at the Tevatron. Using 1.1 fb(-1) of data collected by the CDF II detector, we observe four Lambda b 0 pi+/- resonances in the fully reconstructed decay mode Lambda b 0-->Lambda c + pi-, where Lambda c+-->pK* pi+. We interpret these states as the Sigma b(*)+/- baryons and measure the following masses: m Sigma b+=5807.8 -2.2 +2.0(stat.)+/-1.7(syst.) MeV/c2, m Sigma b- =5815.2+/-1.0(stat.)+/-1.7(syst.) MeV/c2, and m(Sigma b*)-m(Sigma b)=21.2-1.9 +2.0(stat.)-0.3+0.4(syst.) MeV/c2. PMID:18233134

  13. sigma(B) and sigma(L) contribute to Listeria monocytogenes 10403S response to the antimicrobial peptides SdpC and nisin.

    PubMed

    Palmer, M Elizabeth; Wiedmann, Martin; Boor, Kathryn J

    2009-11-01

    The ability of the foodborne pathogen Listeria monocytogenes to survive antimicrobial treatments is a public health concern; therefore, this study was designed to investigate genetic mechanisms contributing to antimicrobial response in L. monocytogenes. In previous studies, the putative bacteriocin immunity gene lmo2570 was predicted to be regulated by the stress responsive alternative sigma factor, sigma(B). As the alternative sigma factor sigma(L) controls expression of genes important for resistance to some antimicrobial peptides, we hypothesized roles for lmo2570, sigma(B), and sigma(L) in L. monocytogenes antimicrobial response. Results from phenotypic characterization of a L. monocytogenes lmo2570 null mutant suggested that this gene does not contribute to resistance to nisin or to SdpC, an antimicrobial peptide produced by some strains of Bacillus subtilis. While lmo2570 transcript levels were confirmed to be sigma(B) dependent, they were sigma(L) independent and were not affected by the presence of nisin under the conditions used in this study. In spot-on-lawn assays with the SdpC-producing B. subtilis EG351, the L. monocytogenes DeltasigB, DeltasigL, and DeltasigB/DeltasigL strains all showed increased sensitivity to SdpC, indicating that both sigma(B) and sigma(L) regulate genes contributing to SdpC resistance. Nisin survival assays showed that sigma(B) and sigma(L) both affect L. monocytogenes sensitivity to nisin in broth survival assays; that is, a sigB null mutant is more resistant than the parent strain to nisin, while a sigB null mutation in DeltasigL background leads to reduced nisin resistance. In summary, while the sigma(B)-dependent lmo2570 does not contribute to resistance of L. monocytogenes to nisin or SdpC, both sigma(B) and sigma(L) contribute to the L. monocytogenes antimicrobial response. PMID:19642919

  14. Sigma receptors and cocaine abuse.

    PubMed

    Narayanan, Sanju; Mesangeau, Christophe; Poupaert, Jacques H; McCurdy, Christopher R

    2011-01-01

    Sigma receptors have been well documented as a protein target for cocaine and have been shown to be involved in the toxic and stimulant actions of cocaine. Strategies to reduce the access of cocaine to sigma receptors have included antisense oligonucleotides to the sigma-1 receptor protein as well as small molecule ligand with affinity for sigma receptor sites. These results have been encouraging as novel protein targets that can attenuate the actions of cocaine are desperately needed as there are currently no medications approved for treatment of cocaine toxicity or addiction. Many years of research in this area have yet to produce an effective treatment and much focus was on dopamine systems. A flurry of research has been carried out to elucidate the role of sigma receptors in the blockade of cocaine effects but this research has yet to yield a clinical agent. This review summarizes the work to date on the linkage of sigma receptors and the actions of cocaine and the progress that has been made with regard to small molecules. Although there is still a lack of an agent in clinical trials with a sigma receptor mechanism of action, work is progressing and the ligands are becoming more selective for sigma systems and the potential remains high. PMID:21050176

  15. The Activity of the Pseudomonas aeruginosa Virulence Regulator σ(VreI) Is Modulated by the Anti-σ Factor VreR and the Transcription Factor PhoB.

    PubMed

    Quesada, Jose M; Otero-Asman, Joaquín R; Bastiaansen, Karlijn C; Civantos, Cristina; Llamas, María A

    2016-01-01

    Gene regulation in bacteria is primarily controlled at the level of transcription initiation by modifying the affinity of the RNA polymerase (RNAP) for the promoter. This control often occurs through the substitution of the RNAP sigma (σ) subunit. Next to the primary σ factor, most bacteria contain a variable number of alternative σ factors of which the extracytoplasmic function group (σ(ECF)) is predominant. Pseudomonas aeruginosa contains nineteen σ(ECF), including the virulence regulator σ(VreI). σ(VreI) is encoded by the vreAIR operon, which also encodes a receptor-like protein (VreA) and an anti-σ factor (VreR). These three proteins form a signal transduction pathway known as PUMA3, which controls expression of P. aeruginosa virulence functions. Expression of the vreAIR operon occurs under inorganic phosphate (Pi) limitation and requires the PhoB transcription factor. Intriguingly, the genes of the σ(VreI) regulon are also expressed in low Pi despite the fact that the σ(VreI) repressor, the anti-σ factor VreR, is also produced in this condition. Here we show that although σ(VreI) is partially active under Pi starvation, maximal transcription of the σ(VreI) regulon genes requires the removal of VreR. This strongly suggests that an extra signal, probably host-derived, is required in vivo for full σ(VreI) activation. Furthermore, we demonstrate that the activity of σ(VreI) is modulated not only by VreR but also by the transcription factor PhoB. Presence of this regulator is an absolute requirement for σ(VreI) to complex the DNA and initiate transcription of the PUMA3 regulon. The potential DNA binding sites of these two proteins, which include a pho box and -10 and -35 elements, are proposed. PMID:27536271

  16. The Activity of the Pseudomonas aeruginosa Virulence Regulator σVreI Is Modulated by the Anti-σ Factor VreR and the Transcription Factor PhoB

    PubMed Central

    Quesada, Jose M.; Otero-Asman, Joaquín R.; Bastiaansen, Karlijn C.; Civantos, Cristina; Llamas, María A.

    2016-01-01

    Gene regulation in bacteria is primarily controlled at the level of transcription initiation by modifying the affinity of the RNA polymerase (RNAP) for the promoter. This control often occurs through the substitution of the RNAP sigma (σ) subunit. Next to the primary σ factor, most bacteria contain a variable number of alternative σ factors of which the extracytoplasmic function group (σECF) is predominant. Pseudomonas aeruginosa contains nineteen σECF, including the virulence regulator σVreI. σVreI is encoded by the vreAIR operon, which also encodes a receptor-like protein (VreA) and an anti-σ factor (VreR). These three proteins form a signal transduction pathway known as PUMA3, which controls expression of P. aeruginosa virulence functions. Expression of the vreAIR operon occurs under inorganic phosphate (Pi) limitation and requires the PhoB transcription factor. Intriguingly, the genes of the σVreI regulon are also expressed in low Pi despite the fact that the σVreI repressor, the anti-σ factor VreR, is also produced in this condition. Here we show that although σVreI is partially active under Pi starvation, maximal transcription of the σVreI regulon genes requires the removal of VreR. This strongly suggests that an extra signal, probably host-derived, is required in vivo for full σVreI activation. Furthermore, we demonstrate that the activity of σVreI is modulated not only by VreR but also by the transcription factor PhoB. Presence of this regulator is an absolute requirement for σVreI to complex the DNA and initiate transcription of the PUMA3 regulon. The potential DNA binding sites of these two proteins, which include a pho box and −10 and −35 elements, are proposed. PMID:27536271

  17. Protein level identification of the Listeria monocytogenes Sigma H, Sigma L, and Sigma C regulons

    PubMed Central

    2013-01-01

    Background Transcriptional regulation by alternative sigma (σ) factors represents an important mechanism that allows bacteria to rapidly regulate transcript and protein levels in response to changing environmental conditions. While the role of the alternative σ factor σB has been comparatively well characterized in L. monocytogenes, our understanding of the roles of the three other L. monocytogenes alternative σ factors is still limited. In this study, we employed a quantitative proteomics approach using Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) to characterize the L. monocytogenes σL, σH, and σC protein regulons. Proteomic comparisons used a quadruple alternative σ factor mutant strain (ΔBCHL) and strains expressing a single alternative σ factor (i.e., σL, σH, and σC; strains ΔBCH, ΔBCL, and ΔBHL) to eliminate potential redundancies between σ factors. Results Among the three alternative σ factors studied here, σH provides positive regulation for the largest number of proteins, consistent with previous transcriptomic studies, while σL appears to contribute to negative regulation of a number of proteins. σC was found to regulate a small number of proteins in L. monocytogenes grown to stationary phase at 37°C. Proteins identified as being regulated by multiple alternative σ factors include MptA, which is a component of a PTS system with a potential role in regulation of PrfA activity. Conclusions This study provides initial insights into global regulation of protein production by the L. monocytogenes alternative σ factors σL, σH, and σC. While, among these σ factors, σH appears to positively regulate the largest number of proteins, we also identified PTS systems that appear to be co-regulated by multiple alternative σ factors. Future studies should not only explore potential roles of alternative σ factors in activating a “cascade” of PTS systems that potentially regulate PrfA, but also may want to explore the

  18. Interaction of a Partially Disordered Antisigma Factor with Its Partner, the Signaling Domain of the TonB-Dependent Transporter HasR

    PubMed Central

    Malki, Idir; Simenel, Catherine; Wojtowicz, Halina; Cardoso de Amorim, Gisele; Prochnicka-Chalufour, Ada; Hoos, Sylviane; Raynal, Bertrand; England, Patrick; Chaffotte, Alain; Delepierre, Muriel; Delepelaire, Philippe; Izadi-Pruneyre, Nadia

    2014-01-01

    Bacteria use diverse signaling pathways to control gene expression in response to external stimuli. In Gram-negative bacteria, the binding of a nutrient is sensed by an outer membrane transporter. This signal is then transmitted to an antisigma factor and subsequently to the cytoplasm where an ECF sigma factor induces expression of genes related to the acquisition of this nutrient. The molecular interactions involved in this transmembrane signaling are poorly understood and structural data on this family of antisigma factor are rare. Here, we present the first structural study of the periplasmic domain of an antisigma factor and its interaction with the transporter. The study concerns the signaling in the heme acquisition system (Has) of Serratia marcescens. Our data support unprecedented partially disordered periplasmic domain of an anti-sigma factor HasS in contact with a membrane-mimicking environment. We solved the 3D structure of the signaling domain of HasR transporter and identified the residues at the HasS−HasR interface. Their conservation in several bacteria suggests wider significance of the proposed model for the understanding of bacterial transmembrane signaling. PMID:24727671

  19. Sigma-model aether

    SciTech Connect

    Carroll, Sean M.; Dulaney, Timothy R.; Gresham, Moira I.; Tam, Heywood

    2009-03-15

    Theories of low-energy Lorentz violation by a fixed-norm 'aether' vector field with two-derivative kinetic terms have a globally bounded Hamiltonian and are perturbatively stable only if the vector is timelike and the kinetic term in the action takes the form of a sigma model. Here we investigate the phenomenological properties of this theory. We first consider the propagation of modes in the presence of gravity and show that there is a unique choice of curvature coupling that leads to a theory without superluminal modes. Experimental constraints on this theory come from a number of sources, and we examine bounds in a two-dimensional parameter space. We then consider the cosmological evolution of the aether, arguing that the vector will naturally evolve to be orthogonal to constant-density hypersurfaces in a Friedmann-Robertson-Walker cosmology. Finally, we examine cosmological evolution in the presence of an extra compact dimension of space, concluding that a vector can maintain a constant projection along the extra dimension in an expanding universe only when the expansion is exponential.

  20. {sigma} Hyperons in the Nucleus

    SciTech Connect

    Bart, S.; Chrien, R. E.; Franklin, W. A.; Fukuda, T.; Hayano, R. S.; Hicks, K.; Hungerford, E. V.; Michael, R.; Miyachi, T.; Nagae, T.

    1999-12-20

    A search for {sigma} hypernuclear states in p -shell hypernuclei has been performed with the Moby Dick spectrometer and the low energy separated beam (LESB-2) at the Brookhaven Alternating Gradient Synchrotron (BNL AGS). Unlike some previously published reports, no narrow states have been observed for targets of {sup 6}Li and {sup 9}Be in (K{sup -}, {pi}{sup {+-}}) reactions, either for bound state or continuum regions. Together with the previously reported J=0 , T=1/2 bound state in {sup 4}{sub {sigma}} He , these results demonstrate the crucial role of isospin in {sigma} hypernuclei. (c) 1999 The American Physical Society.

  1. Alternate Sigma Factor RpoS Is Required for the In Vivo-Specific Repression of Borrelia burgdorferi Plasmid lp54-Borne ospA and lp6.6 Genes

    PubMed Central

    Caimano, Melissa J.; Eggers, Christian H.; Gonzalez, Cynthia A.; Radolf, Justin D.

    2005-01-01

    While numerous positively regulated loci have been characterized during the enzootic cycle of Borrelia burgdorferi, very little is known about the mechanism(s) involved in the repression of borrelial loci either during tick feeding or within the mammalian host. Here, we report that the alternative sigma factor RpoS is required for the in vivo-specific repression of at least two RpoD-dependent B. burgdorferi loci, ospA and lp6.6. The downregulation of ospA and Ip6.6 appears to require either a repressor molecule whose expression is RpoS dependent or an accessory factor which enables RpoS to directly interact with the ospA and Ip6.6 promoter elements, thereby blocking transcription by RpoD. The central role for RpoS during the earliest stages of host adaptation suggests that tick feeding imparts signals to spirochetes that trigger the RpoS-dependent repression, as well as expression, of in vivo-specific virulence factors critical for the tick-to-mammalian host transition. PMID:16267308

  2. Running Head: Implementing Six Sigma Efforts

    ERIC Educational Resources Information Center

    Lindsay, Jamie Eleaitia Mae

    2005-01-01

    Six Sigma is an organization wide program that provides common set of goals, language, and methodology for improving the overall quality of the processes within the organization (Davis & Heineke 2004). Six Sigma main concern is for the customer. What will the customers want? Need? Six Sigma has a model that helps Sigma get implemented DMAIC model…

  3. Statistical software for microcomputers: SigmaPlot 2000 and SigmaStat2

    PubMed

    Kornbrot

    2000-11-01

    I cannot see any advantages for SigmaStat. SigmaPlot does indeed have many excellent features and any psychologist could feel proud of many of the graphs it produces (not the box plots). As to the competition, JMP-IN produces a similar rage of graphs (and a rotating 3D plot for factor analysis), but has much less flexibility about appearance in terms of colours, fills and other features of graph elements. It can also be difficult to make different graphs the same size appear neatly on the page. STATVIEW produces less graph forms, and does not perform the non-linear regression, but has similar excellent control of the colour, form and sizing of different graph elements. Both STATIVEW and JMP-IN have well implemented 'by variable' facilities and produce graphs well linked to their associated statistical analyses. SigmaPlot wins on the flexibility of its error bars. However, EXCEL and other spreadsheets are also well worth considering, as they produce the same range of graphics and are equally flexible over error bars. An experimenter would have to be very sure that the slight advantages in flexibility of presentation from SigmaPlot outweighed the hassle of having to totally re-organize their data. PMID:11109711

  4. An evaluation of the rate of absorption of solar radiation in the O2(X3Sigma-g - b1Sigma-g) transition

    NASA Astrophysics Data System (ADS)

    Mlynczak, Martin G.

    1993-07-01

    The rate at which molecular oxygen absorbs radiation in the O2(X3Sigma-g - b1Sigma-g) transition is calculated using a line-by-line radiative transfer model. This rate is critical to the determination of the population of the O2(b1Sigma-g) state required for studies of the O2(b1Sigma-g - X3Sigma-g) dayglow, the O2(a1Delta-g - X3Sigma-g) dayglow, and possibly the rates of oxidation of H2 and N2O. Previous evaluations of this rate (which is sometimes called the g-factor) have significantly overestimated its value. The rate is tabulated as a function of altitude, pressure, and solar zenith angle.

  5. An evaluation of the rate of absorption of solar radiation in the O2(X3Sigma-g - b1Sigma-g) transition

    NASA Technical Reports Server (NTRS)

    Mlynczak, Martin G.

    1993-01-01

    The rate at which molecular oxygen absorbs radiation in the O2(X3Sigma-g - b1Sigma-g) transition is calculated using a line-by-line radiative transfer model. This rate is critical to the determination of the population of the O2(b1Sigma-g) state required for studies of the O2(b1Sigma-g - X3Sigma-g) dayglow, the O2(a1Delta-g - X3Sigma-g) dayglow, and possibly the rates of oxidation of H2 and N2O. Previous evaluations of this rate (which is sometimes called the g-factor) have significantly overestimated its value. The rate is tabulated as a function of altitude, pressure, and solar zenith angle.

  6. Transition probabilities of the B-prime 1Sigma(u)(+) to X 1Sigma(g)(+) system of molecular hydrogen

    NASA Technical Reports Server (NTRS)

    Kwok, T. L.; Dalgarno, A.; Posen, A.

    1985-01-01

    From published potential energy curves and transition dipole moments, there are obtained by numerical integration of the equations of nuclear motion the vibrational eigenfunctions of the X 1Sigma(g)(+) and B-prime 1Sigma(u)(+) states of H2. The probabilities of radiative transitions from the discrete vibrational levels of the excited B-prime 1Sigma(u)(+) electronic state of H2 to the discrete and continuum vibrational levels of the ground X 1Sigma(g)(+) electronic state are calculated. The Franck-Condon factors are also presented.

  7. Ribosomal Protein S1 Specifically Binds to the 5′ Untranslated Region of the Pseudomonas aeruginosa Stationary-Phase Sigma Factor rpoS mRNA in the Logarithmic Phase of Growth

    PubMed Central

    Ševo, Milica; Buratti, Emanuele; Venturi, Vittorio

    2004-01-01

    The rpoS gene encodes the stationary-phase sigma factor (RpoS or σs), which was identified in several gram-negative bacteria as a central regulator controlling the expression of genes involved in cell survival in response to cessation of growth (stationary phase) and providing cross-protection against various stresses. In Pseudomonas aeruginosa, the levels of σs increase dramatically at the onset of the stationary phase and are regulated at the transcriptional and posttranscriptional levels. The P. aeruginosa rpoS gene is transcribed as a monocistronic rpoS mRNA transcript comprised of an unusually long 373-bp 5′ untranslated region (5′ UTR). In this study, the 5′ UTR and total protein extracts from P. aeruginosa logarithmic and stationary phases of growth were used in order to investigate the protein-RNA interactions that may modulate the translational process. It was observed that a 69-kDa protein, which corresponded to ribosomal protein S1, preferentially binds the 5′ UTR of the rpoS mRNA in the logarithmic phase and not in the stationary phase. This is the first report of a protein-rpoS mRNA 5′ UTR interaction in P. aeruginosa, and the possible involvement of protein S1 in translation regulation of rpoS is discussed. PMID:15262927

  8. Characterization of the genes coding for the putative sigma factor AlgU and its regulators MucA, MucB, MucC, and MucD in Azotobacter vinelandii and evaluation of their roles in alginate biosynthesis.

    PubMed Central

    Martínez-Salazar, J M; Moreno, S; Nájera, R; Boucher, J C; Espín, G; Soberón-Chávez, G; Deretic, V

    1996-01-01

    The study of the biosynthesis of alginate, the exopolysaccharide produced by Azotobacter vinelandii and Pseudomonas aeruginosa, has biotechnological and medical significance. We report here the identification of the A. vinelandii genes coding for the putative sigma factor AlgU and its negative regulators MucA and MucB through the suppression of the highly mucoid phenotype of an A. vinelandii strain by a plasmid encoding MucA and MucB. The sequences of the A. vinelandii algU, mucA, and mucB genes are highly homologous to those of the corresponding P. aeruginosa genes, AlgU shows 93% identity, and MucA and MucB are 64.4 and 63.9% identical, respectively. Forming part of the same operon as algU, mucA, and mucB, two additional genes (mucC and mucD) were identified and sequenced; the product of the former gene is homologous to ORF4 of Photobacterium sp. strain SS9, and that of the latter gene belongs to the HtrA serine protease family. Interestingly, the nonmucoid A. vinelandii UW136 had a 0.9-kb insertion within the algU gene. A strong correlation between AlgU activity and alginate production by A. vinelandii was also found, as reflected in the level of algD transcription. PMID:8606151

  9. Machine Process Capability Information Through Six Sigma

    SciTech Connect

    Lackner, M.F.

    1998-03-13

    A project investigating details concerning machine process capability information and its accessibility has been conducted. The thesis of the project proposed designing a part (denoted as a machine capability workpiece) based on the major machining features of a given machine. Parts are machined and measured to gather representative production, short-term variation. The information is utilized to predict the expected defect rate, expressed in terms of a composite sigma level process capability index, for a production part. Presently, decisions concerning process planning, particularly what machine will statistically produce the minimum amount of defects based on machined features and associated tolerances, are rarely made. Six sigma tools and methodology were employed to conduct this investigation at AlliedSignal FM and T. Tools such as the thought process map, factor relationship diagrams, and components of variance were used. This study is progressing toward completion. This research study was an example of how machine process capability information may be gathered for milling planar faces (horizontal) and slot features. The planning method used to determine where and how to gather variation for the part to be designed is known as factor relationship diagramming. Components-of-variation is then applied to the gathered data to arrive at the contributing level of variation illustrated within the factor relationship diagram. The idea of using this capability information beyond process planning to the other business enterprise operations is proposed.

  10. Crystal Structure of a Group I Energy Coupling Factor Vitamin Transporter S Component in Complex with Its Cognate Substrate.

    PubMed

    Josts, Inokentijs; Almeida Hernandez, Yasser; Andreeva, Antonina; Tidow, Henning

    2016-07-21

    Energy coupling factor (ECF) transporters are responsible for the uptake of essential scarce nutrients in prokaryotes. This ATP-binding cassette transporter family comprises two subgroups that share a common architecture forming a tripartite membrane protein complex consisting of a translocation component and ATP hydrolyzing module and a substrate-capture (S) component. Here, we present the crystal structure of YkoE from Bacillus subtilis, the S component of the previously uncharacterized group I ECF transporter YkoEDC. Structural and biochemical analyses revealed the constituent residues of the thiamine-binding pocket as well as an unexpected mode of vitamin recognition. In addition, our experimental and bioinformatics data demonstrate major differences between YkoE and group II ECF transporters and indicate how group I vitamin transporter S components have diverged from other group I and group II ECF transporters. PMID:27447050

  11. The C-Terminal RpoN Domain of sigma54 Forms an unpredictedHelix-Turn-Helix Motif Similar to domains of sigma70

    SciTech Connect

    Doucleff, Michaeleen; Malak, Lawrence T.; Pelton, Jeffrey G.; Wemmer, David E.

    2005-11-01

    The ''{delta}'' subunit of prokaryotic RNA-polymerase allows gene-specific transcription initiation. Two {sigma} families have been identified, {sigma}{sup 70} and {sigma}{sup 54}, which use distinct mechanisms to initiate transcription and share no detectable sequence homology. Although the {sigma}{sup 70}-type factors have been well characterized structurally by x-ray crystallography, no high-resolution structural information is available for the {sigma}{sup 54}-type factors. Here we present the NMR derived structure of the C-terminal domain of {sigma}{sup 54} from Aquifex aeolicus. This domain (Thr323 to Gly389), which contains the highly conserved RpoN box sequence, consists of a poorly structured N-terminal tail followed by a three-helix bundle, which is surprisingly similar to domains of the {sigma}{sup 70}-type proteins. Residues of the RpoN box, which have previously been shown to be critical for DNA binding, form the second helix of an unpredicted helix-turn-helix motif. This structure's homology with other DNA binding proteins, combined with previous biochemical data, suggest how the C-terminal domain of {sigma}{sup 54} binds to DNA.

  12. The sausage sigma model revisited

    NASA Astrophysics Data System (ADS)

    Suneeta, Vardarajan

    2015-06-01

    Fateev’s sausage sigma models in two and three dimensions are known to be integrable. We study their stability under renormalization group (RG) flow in the target space by using results from the mathematics of Ricci flow. We show that the three-dimensional sausage is unstable, whereas the two-dimensional sausage appears to be stable at least at leading order as it approaches the sphere. We speculate that the stability results obtained are linked to the classification of ancient solutions to Ricci flow (i.e., sigma models that are nonperturbative in the infrared regime) in two and three dimensions. We also describe a class of perturbations of the three-dimensional sausage (with the same continuous symmetries) which remarkably decouple. This indicates that there could be a new solution to RG flow, which is described at least perturbatively as a deformation of the sausage.

  13. Transcription of Ehrlichia chaffeensis Genes Is Accomplished by RNA Polymerase Holoenzyme Containing either Sigma 32 or Sigma 70

    PubMed Central

    Liu, Huitao; Von Ohlen, Tonia; Cheng, Chuanmin; Faburay, Bonto; Ganta, Roman R.

    2013-01-01

    Bacterial gene transcription is initiated by RNA polymerase containing a sigma factor. To understand gene regulation in Ehrlichia chaffeensis, an important tick-transmitted rickettsiae responsible for human monocytic ehrlichiosis, we initiated studies evaluating the transcriptional machinery of several genes of this organism. We mapped the transcription start sites of 10 genes and evaluated promoters of five genes (groE, dnaK, hup, p28-Omp14 and p28-Omp19 genes). We report here that the RNA polymerase binding elements of E. chaffeensis gene promoters are highly homologous for its only two transcription regulators, sigma 32 and sigma 70, and that gene expression is accomplished by either of the transcription regulators. RNA analysis revealed that although transcripts for both sigma 32 and sigma 70 are upregulated during the early replicative stage, their expression patterns remained similar for the entire replication cycle. We further present evidence demonstrating that the organism’s -35 motifs are essential to transcription initiations. The data suggest that E. chaffeensis gene regulation has evolved to support the organism’s growth, possibly to facilitate its intraphagosomal growth. Considering the limited availability of genetic tools, this study offers a novel alternative in defining gene regulation in E. chaffeensis and other related intracellular pathogens. PMID:24278458

  14. An ergonomics investigation into human thermal comfort using an automobile seat heated with encapsulated carbonized fabric (ECF).

    PubMed

    Brooks, J E; Parsons, K C

    1999-05-01

    This report presents the results of an ergonomics investigation into human thermal comfort using an automobile seat heated with an encapsulated carbonized fabric (ECF). Subjective and objective thermal comfort data were recorded while participants sat for 90 min in a heated and a non-heated automobile seat in an environmental chamber. Eight male participants each completed eight experimental sessions in a balanced order repeated measures experimental design. The conditions in the chamber were representative of a range of cool vehicle thermal environments (5, 10, 15 and 20 degrees C; in the 20 degrees C trial participants sat beside a 5 degrees C 'cold wall'). Participants in the heated seat condition used the heating controller with separate temperature control over the back of the seat (squab) and bottom of the seat (cushion) in an effort to maintain their thermal comfort while wearing the provided clothing, which had an estimated insulation value of 0.9 Clo. The trials showed that participants' overall sensations remained higher than 'slightly cool' in the heated seat at all temperatures. Participants' overall discomfort remained lower (i.e. more comfortable) than 'slightly uncomfortable' at temperatures ranging down to nearly 5 degrees C in the heated seat. Hand and foot comfort, sensation and temperature were similar in both seats. Asymmetric torso and thigh skin temperatures were higher in the heated seat although no significant discomfort was found in the front and back of the torso and thigh in either seat. Participants reported no significant difference in alertness between the control and heated seat. PMID:10327890

  15. Synthesis of sigma 29, an RNA polymerase specificity determinant, is a developmentally regulated event in Bacillus subtilis.

    PubMed Central

    Trempy, J E; Morrison-Plummer, J; Haldenwang, W G

    1985-01-01

    Using an immunological probe, we have determined that the synthesis of the Bacillus subtilis RNA polymerase promoter specificity determinant sigma 29 is a developmentally regulated event. sigma 29 is absent from vegetatively growing cells but is abundant in sporulating cells for a restricted (2-h) period during differentiation (hour 2 to hour 4 into the sporeforming process). The narrowness of this period suggests that sigma 29 is a regulatory factor that directs the transcription of a subpopulation of genes at a precise, intermediate stage of spore formation. This view predicts that sigma 29 should be dispensable for early sporulation events. We verified this prediction by an analysis of sigma 29 accumulation in mutants that are blocked at different stages of sporulation in which we show that cells can advance to at least an intermediate point in development (stage III) in the absence of detectable sigma 29. Lastly, our anti-sigma 29 antibody probe detected a second, previously unrecognized protein in Bacillus cell extracts that may be a precursor to sigma 29. This protein, P31 (molecular weight, 31,000) is synthesized earlier in sporulation than is sigma 29. It has a peptide profile that is similar to sigma 29 and is present in all Bacillus subtilis Spo- mutants that were tested and found to still be able to accumulate sigma 29. Images PMID:3918005

  16. Use of a promiscuous, constitutively-active bacterial enhancer-binding protein to define the Sigma54 (RpoN) regulon of Salmonella Typhimurium LT2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Sigma54, or RpoN, is an alternative s factor found widely in eubacteria. A significant complication in analysis of the global sigma54 regulon in a bacterium is that the sigma54 RNA polymerase holoenzyme requires interaction with an active bacterial enhancer-binding protein (bEBP) to init...

  17. Structural determinants of sigma receptor affinity

    SciTech Connect

    Largent, B.L.; Wikstroem, H.G.; Gundlach, A.L.; Snyder, S.H.

    1987-12-01

    The structural determinants of sigma receptor affinity have been evaluated by examining a wide range of compounds related to opioids, neuroleptics, and phenylpiperidine dopaminergic structures for affinity at sigma receptor-binding sites labeled with (+)-(/sup 3/H)3-PPP. Among opioid compounds, requirements for sigma receptor affinity differ strikingly from the determinants of affinity for conventional opiate receptors. Sigma sites display reverse stereoselectivity to classical opiate receptors. Multi-ringed opiate-related compounds such as morphine and naloxone have negligible affinity for sigma sites, with the highest sigma receptor affinity apparent for benzomorphans which lack the C ring of opioids. Highest affinity among opioids and other compounds occurs with more lipophilic N-substituents. This feature is particularly striking among the 3-PPP derivatives as well as the opioids. The butyrophenone haloperidol is the most potent drug at sigma receptors we have detected. Among the series of butyrophenones, receptor affinity is primarily associated with the 4-phenylpiperidine moiety. Conformational calculations for various compounds indicate a fairly wide range of tolerance for distances between the aromatic ring and the amine nitrogen, which may account for the potency at sigma receptors of structures of considerable diversity. Among the wide range of structures that bind to sigma receptor-binding sites, the common pharmacophore associated with high receptor affinity is a phenylpiperidine with a lipophilic N-substituent.

  18. Optimization of steel bar manufacturing process using six sigma

    NASA Astrophysics Data System (ADS)

    Naeem, Khawar; Ullah, Misbah; Tariq, Adnan; Maqsood, Shahid; Akhtar, Rehman; Nawaz, Rashid; Hussain, Iftikhar

    2016-03-01

    Optimization of a manufacturing process results in higher productivity and reduced wastes. Production parameters of a local steel bar manufacturing industry of Pakistan is optimized by using six Sigma-Define, measure, analyze, improve, and controlmethodology. Production data is collected and analyzed. After analysis, experimental design result is used to identify significant factors affecting process performance. The significant factors are controlled to optimized level using two-level factorial design method. A regression model is developed that helps in the estimation of response under multi variable input values. Model is tested, verified, and validated by using industrial data collected at a local steel bar manufacturing industry of Peshawar(Khyber Pakhtunkhwa, Pakistan). The sigma level of the manufacturing process is improved to 4.01 from 3.58. The novelty of the research is the identification of the significant factors along with the optimum levels that affects the process yield, and the methodology to optimize the steel bar manufacturing process.

  19. Electromagnetic Decay of the $\\Sigma^{0}(1385)$ to $\\Lambda\\gamma$

    SciTech Connect

    Keller, Dustin; Adhikari, Krishna; Adikaram-Mudiyanselage, Dasuni; Aghasyan, Mher; Amaryan, Moscov; Baghdasaryan, Hovhannes; Ball, J P; Ball, Jacques; Battaglieri, Marco; Batourine, V; Bedlinskiy, Ivan; Bennett, Robert; Biselli, Angela; Branford, Derek; Briscoe, Wilbert; Brooks, William; Burkert, Volker; Careccia, Sharon; Carman, Daniel; Casey, Liam; Cole, Philip; Contalbrigo, Marco; Crede, Volker; D'Angelo, Annalisa; Daniel, AJI; Dashyan, Natalya; De Vita, Raffaella; De Sanctis, Enzo; Deur, Alexandre; Dey, Biplap; Dickson, Richard; Djalali, Chaden; Doughty, David; Dupre, Raphael; Egiyan, Hovanes; El Alaoui, Ahmed; Elfassi, Lamiaa; Eugenio, Paul; Fedotov, Gleb; Fegan, Stuart; Forest, Tony; Gabrielyan, Marianna; Gavalian, Gagik; Gevorgyan, Nerses; Giovanetti, Kevin; Girod, Francois-Xavier; Gohn, Wesley; Golovach, Evgeny; Gothe, Ralf; Graham, Lewis; Guidal, Michel; Guegan, Baptiste; Hafidi, Kawtar; Hakobyan, Hayk; Hanretty, Charles; Holtrop, Maurik; Ilieva, Yordanka; Ireland, David; Isupov, Evgeny; Jawalkar, Sucheta; Jenkins, David; Jo, Hyon-Suk; Joo, Kyungseon; Khandaker, Mahbubul; Khetarpal, Puneet; Kim, Andrey; Kim, Wooyoung; Klein, Andreas; Klein, Franz; Konczykowski, Piotr; Kubarovsky, Valery; Kuleshov, Sergey; Kuznetsov, Viacheslav; Lu, Haiyun; MacGregor, Ian; Markov, Nikolai; McAndrew, Josephine; KcKinnon, Bryan; Meyer, Curtis; Micherdzinska, Anna; Mirazita, Marco; Mokeev, Viktor; Moreno, Brahim; Moriya, Kei; Morrison, Brian; Moutarde, Herve; Munevar Espitia, Edwin; Nadel-Turonski, Pawel; Ni, Andrey; Niccolai, Silvia; Niculescu, Gabriel; Niculescu, Maria-Ioana; Osipenko, Mikhail; Ostrovidov, Alexander; Paremuzyan, Rafayel; Park, Kijun; Park, Sungkyun; Pasyuk, Eugene; Pasyuk, Evgueni; Pereira, Sergio; Pappalardo, Luciano; Pisano, Silvia; Pogorelko, Oleg; Pozdnyakov, Sergey; Price, John; Procureur, Sebastien; Protopopescu, Dan; Raue, Brian; Ripani, Marco; Ritchie, Barry; Rosner, Guenther; Rossi, Patrizia; Sabatie, Franck; Saini, Mukesh; Salgado, Carlos; Schott, Diane; Schumacher, Reinhard; Seder, Erin; Seraydaryan, Heghine; Sharabian, Youri; Smith, Elton; Smith, Gregory; Sober, Daniel; Stepanyan, Stepan; Stoler, Paul; Strakovski, Igor; Strauch, Steffen; Taiuti, Mauro; Tang, Wei; Taylor, Charles; Vernarsky, Brian; Vineyard, Michael; Voutier, Eric; Weinstein, Lawrence; Watts, Daniel; Wood, Michael; Zachariou, Nicholas; Zana, Lorenzo; Zhao, Bo; Zhao, Zhiwen

    2011-04-01

    The electromagnetic decay $\\Sigma^0(1385) \\to \\Lambda \\gamma$ was studied using the CLAS detector at the Thomas Jefferson National Accelerator Facility. A real photon beam with a maximum energy of 3.8 GeV was incident on a proton target, producing an exclusive final state of $K^+\\Sigma^{*0}$. We report the decay widths ratio $\\Sigma^0(1385) \\to \\Lambda\\gamma$/ $\\Sigma^0(1385) \\to \\Lambda\\pi^0$ = $1.42 \\pm 0.12(\\text{stat})_{-0.07}^{+0.11}(\\text{sys})$%. This ratio is larger than most theoretical predictions by factors ranging from 1.5-3, but is consistent with the only other experimental measurement. From the reported ratio we calculate the partial width and electromagnetic transition magnetic moment for $\\Sigma^0(1385) \\to \\Lambda\\gamma$.

  20. Sigma 2 Graphic Display Software Program Description

    NASA Technical Reports Server (NTRS)

    Johnson, B. T.

    1973-01-01

    A general purpose, user oriented graphic support package was implemented. A comprehensive description of the two software components comprising this package is given: Display Librarian and Display Controller. These programs have been implemented in FORTRAN on the XDS Sigma 2 Computer Facility. This facility consists of an XDS Sigma 2 general purpose computer coupled to a Computek Display Terminal.

  1. Effects of sigmaS and the transcriptional activator AppY on induction of the Escherichia coli hya and cbdAB-appA operons in response to carbon and phosphate starvation.

    PubMed Central

    Atlung, T; Knudsen, K; Heerfordt, L; Brøndsted, L

    1997-01-01

    The transcriptional regulation of two energy metabolism operons, hya and cbdAB-appA, has been investigated during carbon and phosphate starvation. The hya operon encodes hydrogenase 1, and the cbdAB-appA operon encodes cytochrome bd-II oxidase and acid phosphatase, pH 2.5. Both operons are targets for the transcriptional activator AppY. In exponential growth, expression of the hya and cbd operons was reduced in an rpoS mutant lacking the RNA polymerase sigmaS factor, and the induction of the two operons by entry into stationary phase in rich medium was strongly dependent on sigmaS. Both operons were induced by carbon starvation, but only induction of the hya operon was dependent on sigmaS, whereas that of the cbd promoter was dependent on AppY. The appY gene also showed sigmaS-dependent induction by carbon starvation. The cbd and hya operons were also found to exhibit a sigmaS-dependent transient twofold induction by osmotic upshift. Like the cbd operon, the hya operon was highly induced by phosphate starvation. For both operons the induction was strongly dependent on AppY. The induction ratio of the two operons was the same in rpoS+ and rpoS mutant strains, indicating that the phosphate starvation-induced increase in sigmaS concentration is not involved in the phosphate regulation of these operons. PMID:9079897

  2. Effects of sigmaS and the transcriptional activator AppY on induction of the Escherichia coli hya and cbdAB-appA operons in response to carbon and phosphate starvation.

    PubMed

    Atlung, T; Knudsen, K; Heerfordt, L; Brøndsted, L

    1997-04-01

    The transcriptional regulation of two energy metabolism operons, hya and cbdAB-appA, has been investigated during carbon and phosphate starvation. The hya operon encodes hydrogenase 1, and the cbdAB-appA operon encodes cytochrome bd-II oxidase and acid phosphatase, pH 2.5. Both operons are targets for the transcriptional activator AppY. In exponential growth, expression of the hya and cbd operons was reduced in an rpoS mutant lacking the RNA polymerase sigmaS factor, and the induction of the two operons by entry into stationary phase in rich medium was strongly dependent on sigmaS. Both operons were induced by carbon starvation, but only induction of the hya operon was dependent on sigmaS, whereas that of the cbd promoter was dependent on AppY. The appY gene also showed sigmaS-dependent induction by carbon starvation. The cbd and hya operons were also found to exhibit a sigmaS-dependent transient twofold induction by osmotic upshift. Like the cbd operon, the hya operon was highly induced by phosphate starvation. For both operons the induction was strongly dependent on AppY. The induction ratio of the two operons was the same in rpoS+ and rpoS mutant strains, indicating that the phosphate starvation-induced increase in sigmaS concentration is not involved in the phosphate regulation of these operons. PMID:9079897

  3. Epitope mapping and functional analysis of sigma A and sigma NS proteins of avian reovirus

    SciTech Connect

    Huang, Pi H.; Li, Ying J.; Su, Yu P.; Lee, Long H.; Liu, Hung J. . E-mail: hjliu@mail.npust.edu.tw

    2005-02-20

    We have previously shown that avian reovirus (ARV) {sigma}A and {sigma}NS proteins possess dsRNA and ssRNA binding activity and suggested that there are two epitopes on {sigma}A (I and II) and three epitopes (A, B, and C) on {sigma}NS. To further define the location of epitopes on {sigma}A and {sigma}NS proteins and to further elucidate the biological functions of these epitopes by using monoclonal antibodies (MAbs) 62, 1F9, H1E1, and 4A123 against the ARV S1133 strain, the full-length and deletion fragments of S2 and S4 genes of ARV generated by polymerase chain reaction (PCR) were cloned into pET32 expression vectors and the fusion proteins were overexpressed in Escherichia coli BL21 strain. Epitope mapping using MAbs and E. coli-expressed deletion fragments of {sigma}A and {sigma}NS of the ARV S1133 strain, synthetic peptides, and the cross reactivity of MAbs to heterologous ARV strains demonstrated that epitope II on {sigma}A was located at amino acid residues {sup 340}QWVMAGLVSAA{sup 350} and epitope B on {sigma}NS at amino acid residues {sup 180}MLDMVDGRP{sup 188}. The MAbs (62, 1F9, and H1E1) directed against epitopes II and B did not require the native conformation of {sigma}A and {sigma}NS, suggesting that their binding activities were conformation-independent. On the other hand, MAb 4A123 only reacted with complete {sigma}NS but not with truncated {sigma}NS fusion proteins in Western blot, suggesting that the binding activity of MAb to epitope A on {sigma}NS was conformation-dependent. Amino acid sequence analysis and the binding assays of MAb 62 to heterologous ARV strains suggested that epitope II on {sigma}A was highly conserved among ARV strains and that this epitope is suitable as a serological marker for the detection of ARV antibodies following natural infection in chickens. On the contrary, an amino acid substitution at position 183 (M to V) in epitope B of ARV could hinder the reactivity of the {sigma}NS with MAb 1F9. The {sigma}NS of ARV with ss

  4. Search for Sigma--Delta hypernuclear conversion

    NASA Astrophysics Data System (ADS)

    Bukhari, Masroor Hassan Haider Shah

    This research was aimed at the study of the in-flight A=3 (K- , pi+/-) reactions leading to in situ nuclear formation of a Sigma hyperon, its interactions with nucleons, and subsequent conversion into a Λ hyperon. The analysis was based upon the data from the Brookhaven National Laboratory experiment E774 carried out at the Alternating Gradient Synchrotron. This experiment comprised a two-layered scintillation counting barrel detector and two spectrometers to detect the missing mass in the reaction on a 3He target, resulting in the Sigma hypernucleus formation. A Monte Carlo simulation of the experiment was written within the framework of the GEANT simulation tool, incorporating physics generators for all the involved channels and the technique of multiplicity tagging. The objective was to obtain and analyze the relevant multiplicities of the involved channels which could result from the primary reaction. Analysis of results from simulations and their comparison with the experimental data revealed insight into the interactions of a Sigma within the nucleus and helped identify the multiplicities which corresponded to the true Sigma-Λ conversion events. On the basis of this analysis, the three-body system SigmaNN in the s-shell and the SigmaN → ΛN conversion were investigated. In the second phase of this study, a theoretical model for the calculation of scattering parameters and relative cross section for (Sigma-.2 H) production leading to Sigma-Λ conversion was developed. This was based on the effective range expansion and a plane wave impulse approximation (PWIA) paradigm. Both the scattering and absorption amplitudes, corresponding to s-wave SigmaSigma and SigmaΛ scattering states, respectively, were calculated. Finally the parameters (and corresponding cross section) were extracted by fitting the simulated model to the experiment data. The nature of the obtained parameters and shape of the cross section shed significant light on the Sigma-Λ conversion

  5. SIGMA WEB INTERFACE FOR REACTOR DATA APPLICATIONS

    SciTech Connect

    Pritychenko,B.; Sonzogni, A.A.

    2010-05-09

    We present Sigma Web interface which provides user-friendly access for online analysis and plotting of the evaluated and experimental nuclear reaction data stored in the ENDF-6 and EXFOR formats. The interface includes advanced browsing and search capabilities, interactive plots of cross sections, angular distributions and spectra, nubars, comparisons between evaluated and experimental data, computations for cross section data sets, pre-calculated integral quantities, neutron cross section uncertainties plots and visualization of covariance matrices. Sigma is publicly available at the National Nuclear Data Center website at http://www.nndc.bnl.gov/sigma.

  6. Interaction of sigma 70 with Escherichia coli RNA polymerase core enzyme studied by surface plasmon resonance.

    PubMed

    Ferguson, A L; Hughes, A D; Tufail, U; Baumann, C G; Scott, D J; Hoggett, J G

    2000-09-22

    The interaction between the core form of bacterial RNA polymerases and sigma factors is essential for specific promoter recognition, and for coordinating the expression of different sets of genes in response to varying cellular needs. The interaction between Escherichia coli core RNA polymerase and sigma 70 has been investigated by surface plasmon resonance. The His-tagged form of sigma 70 factor was immobilised on a Ni2+-NTA chip for monitoring its interaction with core polymerase. The binding constant for the interaction was found to be 1.9x10(-7) M, and the dissociation rate constant for release of sigma from core, in the absence of DNA or transcription, was 4x10(-3) s(-1), corresponding to a half-life of about 200 s. PMID:11007979

  7. Pharmacological and autoradiographic characterization of sigma receptors

    SciTech Connect

    Largent, B.L.

    1986-01-01

    The existence of three types of opioid receptors - ..mu.., kappa, and sigma - was postulated to explain the effects of different opioids in the chronic spinal dog. Sigma receptors, named for the prototypic agonist SKF 10,047 (N-allylnormetazocine), were suggested to mediate the psychotomimetic-like effects of SKF 10,047 in the dog. 3-(3-Hydroxyphenyl)-N-(1-propyl)piperidine (3-PPP) has been proposed as a selective dopamine autoreceptor agonist. However, the drug specificity of (+)(/sup 3/H)3-PPP binding in brain is identical to that of sigma receptor binding sites which may mediate psychotomimetic effects of some opioids. Pharmacological and autoradiographic analyses reveal that (+)(/sup 3/H)SKF 10,047, the prototypic sigma agonist, labels two sites in brain. The drug specificity of the high affinity site for (+)(/sup 3/H)SKF 10,047 resembles that of putative sigma receptors labeled with (+)(/sup 3/H)3-PPP, being potently inhibited by (+)3-PPP, haloperidol, and (+/-)pentazocine, and demonstrating stereoselectivity for the (+) isomer of SKF 10,047. Autoradiographic localizations of high affinity (+)(/sup 3/H)SKF 10,047 binding sites closely resemble those of (+)(/sup 3/H)3-PPP labeled sites with high levels of binding in the hippocampal pyramidal cell layer, hypothalamus, and pontine and cranial nerve nuclei. Thus, putative sigma receptors and PCP receptors represent distinct receptor populations in brain. This proposal is supported by the presence of sigma binding sites - and absence of PCP receptors - on NCB-20 cell membranes, a hybrid neurotumor cell line that provides a model system for the physiological and biochemical study of sigma receptors.

  8. Inclusive Sigma- photoproduction on the neutron via the reaction gamma n (p) ---> K+ Sigma- (p)

    SciTech Connect

    Jorn Langheinrich; Ana Lima; Barry Berman

    2006-06-01

    The analysis described here is part of a comprehensive survey of the elementary strangeness photoproduction cross sections on the nucleon. The six elementary strangeness reactions are {gamma}n {yields} K{sup 0}{Lambda} and {gamma}p {yields} K{sup +}{Lambda} {gamma}n {yields} K{sup 0}{Sigma}{sup 0} and {gamma}p {yields} K{sup +}{Sigma}{sup 0} {gamma}n {yields} K{sup +}{Sigma}{sup -} and {gamma}p {yields} K{sup 0}{Sigma}|{sup +}

  9. Towards Resolving the Crab Sigma-Problem: A Linear Accelerator?

    NASA Technical Reports Server (NTRS)

    Contopoulos, Ioannis; Kazanas, Demosthenes; White, Nicholas E. (Technical Monitor)

    2002-01-01

    Using the exact solution of the axisymmetric pulsar magnetosphere derived in a previous publication and the conservation laws of the associated MHD flow, we show that the Lorentz factor of the outflowing plasma increases linearly with distance from the light cylinder. Therefore, the ratio of the Poynting to particle energy flux, generically referred to as sigma, decreases inversely proportional to distance, from a large value (typically approx. greater than 10(exp 4)) near the light cylinder to sigma approx. = 1 at a transition distance R(sub trans). Beyond this distance the inertial effects of the outflowing plasma become important and the magnetic field geometry must deviate from the almost monopolar form it attains between R(sub lc), and R(sub trans). We anticipate that this is achieved by collimation of the poloidal field lines toward the rotation axis, ensuring that the magnetic field pressure in the equatorial region will fall-off faster than 1/R(sup 2) (R being the cylindrical radius). This leads both to a value sigma = a(sub s) much less than 1 at the nebular reverse shock at distance R(sub s) (R(sub s) much greater than R(sub trans)) and to a component of the flow perpendicular to the equatorial component, as required by observation. The presence of the strong shock at R = R(sub s) allows for the efficient conversion of kinetic energy into radiation. We speculate that the Crab pulsar is unique in requiring sigma(sub s) approx. = 3 x 10(exp -3) because of its small translational velocity, which allowed for the shock distance R(sub s) to grow to values much greater than R(sub trans).

  10. Six Lessons We Learned Applying Six Sigma

    NASA Technical Reports Server (NTRS)

    Carroll, Napoleon; Casleton, Christa H.

    2005-01-01

    As Chief Financial Officer of Kennedy Space Center (KSC), I'm not only responsible for financial planning and accounting but also for building strong partnerships with the CFO customers, who include Space Shuttle and International Space Station operations as well all who manage the KSC Spaceport. My never ending goal is to design, manage and continuously improve our core business processes so that they deliver world class products and services to the CFO's customers. I became interested in Six Sigma as Christa Casleton (KSC's first Six Sigma Black belt) applied Six Sigma tools and methods to our Plan and Account for Travel Costs Process. Her analysis was fresh, innovative and thorough but, even more impressive, was her approach to ensure ongoing, continuous process improvement. Encouraged by the results, I launched two more process improvement initiatives aimed at applying Six Sigma principles to CFO processes that not only touch most of my employees but also have direct customer impact. As many of you know, Six Sigma is a measurement scale that compares the output of a process with customer requirements. That's straight forward, but demands that you not only understand your processes but also know your products and the critical customer requirements. The objective is to isolate and eliminate the causes of process variation so that the customer sees consistently high quality.

  11. LINE ABSORPTION OSCILLATOR STRENGTHS FOR THE c'{sub 4}{sup 1}{Sigma}{sup +}{sub u}(3)-X{sup 1}{Sigma}{sup +}{sub g}(0-5) BANDS IN N{sub 2}

    SciTech Connect

    Lavin, C.; Velasco, A. M.

    2011-09-20

    Theoretical absorption oscillator strengths and emission branching ratios for rotational lines of the c'{sub 4}{sup 1}{Sigma}{sup +}{sub u}(3)-X{sup 1}{Sigma}{sup +}{sub g}(0-5) bands of molecular nitrogen are reported. The calculations have been performed with the molecular quantum defect orbital method, which has proved to be reliable in previous studies of rovibronic transitions in diatomic molecules. The strong interaction between c'{sub 4}{sup 1}{Sigma}{sup +}{sub u}(3) and b' {sup 1}{Sigma}{sup +}{sub u}(10) states has been analyzed through an interaction matrix that includes rotational terms. Owing to the perturbation, the c'{sub 4}{sup 1}{Sigma}{sup +}{sub u}(3)-X{sup 1}{Sigma}{sup +}{sub g}(0), c'{sub 4}{sup 1}{Sigma}{sup +}{sub u}(3)-X{sup 1}{Sigma}{sup +}{sub g}(1), and c'{sub 4}{sup 1}{Sigma}{sup +}{sub u}(3)-X{sup 1}{Sigma}{sup +}{sub g}(5) bands are not weak, in contrast to what would be expected on the basis of the Franck-Condon principle. Moreover, the intensity distribution of the rotational lines within each of the vibronic bands deviates from considerations based on Hoenl-London factors. In this work, we provide data that may be useful to interpret spectra from atmospheres of the Earth, Titan, and Triton, in which transitions from the c'{sub 4}{sup 1}{Sigma}{sup +}{sub u}(3) level have been detected.

  12. Production of element correction factors for thermoluminescent dosimeters

    SciTech Connect

    Plato, P.; Miklos, J.

    1985-11-01

    Approximately 80 processors of personal dosimetry in the United States use thermoluminescent dosimeters (TLDs). Recent demands that dosimetry processors be able to measure radiation doses to within +/- 50% of the correct value have focused attention on the reproducibility of the TL elements within each TLD. The phosphors for these TLDs are manufactured by three companies. A dosimetry processor faces three options concerning the quality of the TL elements purchased; trust the supplier's quality control program, screen new TL elements and discard those that are extremely bad, or use element correction factors (ECFs). The first option results in dosimetry processors failing the +/- 50% accuracy requirement due to excessive variability among the TL elements. The second option still permits large precision errors that come close to the +/- 50% accuracy requirement. This paper advocates the third option and presents a 10-step procedure to produce ECFs. The procedure ensures that the ECFs represent only variations among the TL elements and not variations caused by stability problems with the TLD reader. Following is an example of ECF production for 3000 TLDs.

  13. Sigma-nucleus potential in A=28.

    PubMed

    Noumi, H; Saha, P K; Abe, D; Ajimura, S; Aoki, K; Bhang, H C; Endo, T; Fujii, Y; Fukuda, T; Guo, H C; Imai, K; Hashimoto, O; Hotchi, H; Kim, E H; Kim, J H; Kishimoto, T; Krutenkova, A; Maeda, K; Nagae, T; Nakamura, M; Outa, H; Sekimoto, M; Saito, T; Sakaguchi, A; Sato, Y; Sawafta, R; Shimizu, Y; Takahashi, T; Tang, L; Tamura, H; Tanida, K; Watanabe, T; Xia, H H; Zhou, S H; Zhu, L H; Zhu, X F

    2002-08-12

    We have studied the (pi(-),K+) reaction on a silicon target to investigate the sigma-nucleus potential. The inclusive spectrum was measured at a beam momentum of 1.2 GeV/c with an energy resolution of 3.3 MeV (FWHM) by employing the superconducting kaon spectrometer system. The spectrum was compared with theoretical calculations within the framework of the distorted-wave impulse approximation, which demonstrates that a strongly repulsive sigma-nucleus potential with a nonzero size of the imaginary part reproduces the observed spectrum. PMID:12190516

  14. A Lean Six Sigma journey in radiology.

    PubMed

    Bucci, Ronald V; Musitano, Anne

    2011-01-01

    The department of radiology at Akron Children's Hospital embarked on a Lean Six Sigma mission as part of a hospital wide initiative to show increased customer satisfaction, reduce employee dissatisfaction and frustration, and decrease costs. Three processes that were addressed were reducing the MRI scheduling back-log, reconciling discrepancies in billing radiology procedures, and implementing a daily management system. Keys to success is that managers provide opportunities to openly communicate between department sections to break down barriers. Executive leaders must be engaged in Lean Six Sigma for the company to be successful. PMID:21793459

  15. A K3 sigma model with : symmetry

    NASA Astrophysics Data System (ADS)

    Gaberdiel, Matthias R.; Taormina, Anne; Volpato, Roberto; Wendland, Katrin

    2014-02-01

    The K3 sigma model based on the -orbifold of the D 4-torus theory is studied. It is shown that it has an equivalent description in terms of twelve free Majorana fermions, or as a rational conformal field theory based on the affine algebra . By combining these different viewpoints we show that the = (4 , 4) preserving symmetries of this theory are described by the discrete symmetry group : . This model therefore accounts for one of the largest maximal symmetry groups of K3 sigma models. The symmetry group involves also generators that, from the orbifold point of view, map untwisted and twisted sector states into one another.

  16. All optical binary delta-sigma modulator

    NASA Astrophysics Data System (ADS)

    Sayeh, Mohammad R.; Siahmakoun, Azad

    2005-09-01

    This paper describes a novel A/D converter called "Binary Delta-Sigma Modulator" (BDSM) which operates only with nonnegative signal with positive feedback and binary threshold. This important modification to the conventional delta-sigma modulator makes the high-speed (>100GHz) all-optical implementation possible. It has also the capability to modify its own sampling frequency as well as its input dynamic range. This adaptive feature helps designers to optimize the system performance under highly noisy environment and also manage the power consumption of the A/D converters.

  17. Identification of sigma S-regulated genes in Salmonella typhimurium: complementary regulatory interactions between sigma S and cyclic AMP receptor protein.

    PubMed Central

    Fang, F C; Chen, C Y; Guiney, D G; Xu, Y

    1996-01-01

    sigma S (RpoS)-regulated lacZ transcriptional fusions in Salmonella typhimurium were identified from a MudJ transposon library by placing the rpoS gene under the control of the araBAD promoter and detecting lacZ expression in the presence or absence of arabinose supplementation. Western blot (immunoblot) analysis of bacteria carrying PBAD::rpoS demonstrated arabinose-dependent rpoS expression during all phases of growth. sigma S-dependent gene expression of individual gene fusions was confirmed by P22-mediated transduction of the MudJ insertions into wild-type or rpoS backgrounds. Analysis of six insertions revealed the known sigma S-regulated gene otsA, as well as five novel loci. Each of these genes is maximally expressed in stationary phase, and all but one show evidence of cyclic AMP receptor protein-dependent repression during logarithmic growth which is relieved in stationary phase. For these genes, as well as for the sigma S-regulated spvB plasmid virulence gene, a combination of rpoS overexpression and crp inactivation can result in high-level expression during logarithmic growth. The approach used to identify sigma S-regulated genes in this study provides a general method for the identification of genes controlled by trans-acting regulatory factors. PMID:8752327

  18. Extracytoplasmic Function σ Factors with Overlapping Promoter Specificity Regulate Sublancin Production in Bacillus subtilis▿ †

    PubMed Central

    Luo, Yun; Helmann, John D.

    2009-01-01

    Bacillus subtilis harbors seven extracytoplasmic function (ECF) σ factors. At least three ECF σ factors (σM, σW, and σX) are induced by, and provide resistance to, antibiotics and other agents eliciting cell envelope stress. Here, we report that ECF σ factors also contribute to antibiotic production. B. subtilis 168 strains that are lysogenic for the SPβ bacteriophage produce sublancin, which inhibits the growth of other, nonlysogenic strains. Genetic studies demonstrate that synthesis of sublancin is largely dependent on σX, with a smaller contribution from σM. A sigM sigX double mutant is unable to produce sublancin. This defect is primarily due to the fact that the sublancin biosynthesis is positively activated by the transition state regulator and AbrB paralog Abh, which counteracts transcriptional repression of the sublancin biosynthesis operon by AbrB. Ectopic expression of abh bypasses the requirement for σM or σX in sublancin synthesis, as does an abrB mutation. In addition to their major role in regulating sublancin expression by activating abh transcription, σX and σM also have a second role as positive regulators of sublancin expression that is independent of AbrB and Abh. Since sublancin resistance in nonlysogens is largely dependent on σW, ECF σ factors control both sublancin production and resistance. PMID:19465659

  19. Improving Learning Outcome Using Six Sigma Methodology

    ERIC Educational Resources Information Center

    Tetteh, Godson A.

    2015-01-01

    Purpose: The purpose of this research paper is to apply the Six Sigma methodology to identify the attributes of a lecturer that will help improve a student's prior knowledge of a discipline from an initial "x" per cent knowledge to a higher "y" per cent of knowledge. Design/methodology/approach: The data collection method…

  20. Need of Six Sigma in Education

    ERIC Educational Resources Information Center

    Mehrotra, Dheeraj

    2007-01-01

    The marching trend of the new economic order has generated a new capsule of SIX SIGMA as a unified approach to process excellence. The tests reveal that it has transformed some of the most successful companies in the world like Motorola, GE etc. It is activated as an approach to aiming at the target by changing the culture of a company, involving…

  1. Do narrow {Sigma}-hypernuclear states exist?

    SciTech Connect

    Chrien, R.E.

    1995-12-31

    Reports of narrow states in {Sigma}-hypernucleus production have appeared from time to time. The present experiment is a repeat of the first and seemingly most definitive such experiment, that on a target of {sup 9}Be, but with much better statistics. No narrow states were observed.

  2. How Six Sigma Methodology Improved Doctors' Performance

    ERIC Educational Resources Information Center

    Zafiropoulos, George

    2015-01-01

    Six Sigma methodology was used in a District General Hospital to assess the effect of the introduction of an educational programme to limit unnecessary admissions. The performance of the doctors involved in the programme was assessed. Ishikawa Fishbone and 5 S's were initially used and Pareto analysis of their findings was performed. The results…

  3. Six Sigma and Introductory Statistics Education

    ERIC Educational Resources Information Center

    Maleyeff, John; Kaminsky, Frank C.

    2002-01-01

    A conflict exists between the way statistics is practiced in contemporary business environments and the way statistics is taught in schools of management. While businesses are embracing programs, such as six sigma and TQM, that bring statistical methods to the forefront of management decision making, students do not graduate with the skills to…

  4. The science of Six Sigma in hospitals.

    PubMed

    Guinane, Carole S; Davis, Noreen H

    2004-01-01

    Six Sigma applied to hospital processes and services can lead to breakthrough improvements, near-perfect outcomes, and zero defects. It is wise to consider this aspect of quality science as part of an overall Total Quality Management program. Senior leadership support and involvement is critical to the success of this strategy. PMID:15604839

  5. Quasifree Electroproduction of Lambda, Sigma0, and sigma-Hyperons on Carbon and Aluminum

    SciTech Connect

    Wendy Hinton

    2001-05-01

    The first study of (e,e',K+) on carbon and aluminum was performed at Thomas Jefferson National Accelerator Facility (Jefferson Lab) using the Continuous Electron Beam Accelerator Facility (CEBAF). The scattered electron and electroproduced kaon were detected in coincidence in the Hall C End Station using the High Momentum Spectrometer and Short Orbit Spectrometer. The quasifree production of the Lambda, Sigma0, and Sigma- hyperons was studied. The Lambda-dependence of the effective nucleon number was obtained. The cross section data were fit to a power law ({approx}Aa) with a = 0.88 +/- 0.10, consistent with the K+'s relatively long nuclear mean free path. A large enhancement in the Sigma0+Sigma- / Lambda ratio is seen. A feasibility test for hypernuclear spectroscopy on C-12 and Al-27 with the HMS-SOS was performed.

  6. Six Sigma methods applied to cryogenic coolers assembly line

    NASA Astrophysics Data System (ADS)

    Ventre, Jean-Marc; Germain-Lacour, Michel; Martin, Jean-Yves; Cauquil, Jean-Marc; Benschop, Tonny; Griot, René

    2009-05-01

    Six Sigma method have been applied to manufacturing process of a rotary Stirling cooler: RM2. Name of the project is NoVa as main goal of the Six Sigma approach is to reduce variability (No Variability). Project has been based on the DMAIC guideline following five stages: Define, Measure, Analyse, Improve, Control. Objective has been set on the rate of coolers succeeding performance at first attempt with a goal value of 95%. A team has been gathered involving people and skills acting on the RM2 manufacturing line. Measurement System Analysis (MSA) has been applied to test bench and results after R&R gage show that measurement is one of the root cause for variability in RM2 process. Two more root causes have been identified by the team after process mapping analysis: regenerator filling factor and cleaning procedure. Causes for measurement variability have been identified and eradicated as shown by new results from R&R gage. Experimental results show that regenerator filling factor impacts process variability and affects yield. Improved process haven been set after new calibration process for test bench, new filling procedure for regenerator and an additional cleaning stage have been implemented. The objective for 95% coolers succeeding performance test at first attempt has been reached and kept for a significant period. RM2 manufacturing process is now managed according to Statistical Process Control based on control charts. Improvement in process capability have enabled introduction of sample testing procedure before delivery.

  7. Sample Dilution and Bacterial Community Composition Influence Empirical Leucine-to-Carbon Conversion Factors in Surface Waters of the World's Oceans

    PubMed Central

    Hernando-Morales, Víctor; Cornejo-Castillo, Francisco M.; Alonso-Sáez, Laura; Sarmento, Hugo; Valencia-Vila, Joaquín; Serrano Catalá, Teresa; Hernández-Ruiz, Marta; Varela, Marta M.; Ferrera, Isabel; Gutiérrez Morán, Xosé Anxelu; Gasol, Josep M.

    2015-01-01

    The transformation of leucine incorporation rates to prokaryotic carbon production rates requires the use of either theoretical or empirically determined conversion factors. Empirical leucine-to-carbon conversion factors (eCFs) vary widely across environments, and little is known about their potential controlling factors. We conducted 10 surface seawater manipulation experiments across the world's oceans, where the growth of the natural prokaryotic assemblages was promoted by filtration (i.e., removal of grazers [F treatment]) or filtration combined with dilution (i.e., also relieving resource competition [FD treatment]). The impact of sunlight exposure was also evaluated in the FD treatments, and we did not find a significant effect on the eCFs. The eCFs varied from 0.09 to 1.47 kg C mol Leu−1 and were significantly lower in the FD than in the F samples. Also, changes in bacterial community composition during the incubations, as assessed by automated ribosomal intergenic spacer analysis (ARISA), were more pronounced in the FD than in the F treatments, compared to unmanipulated controls. Thus, we discourage the common procedure of diluting samples (in addition to filtration) for eCF determination. The eCFs in the filtered treatment were negatively correlated with the initial chlorophyll a concentration, picocyanobacterial abundance (mostly Prochlorococcus), and the percentage of heterotrophic prokaryotes with high nucleic acid content (%HNA). The latter two variables explained 80% of the eCF variability in the F treatment, supporting the view that both Prochlorococcus and HNA prokaryotes incorporate leucine in substantial amounts, although this results in relatively low carbon production rates in the oligotrophic ocean. PMID:26407885

  8. Operational excellence (six sigma) philosophy: Application to software quality assurance

    SciTech Connect

    Lackner, M.

    1997-11-01

    This report contains viewgraphs on operational excellence philosophy of six sigma applied to software quality assurance. This report outlines the following: goal of six sigma; six sigma tools; manufacturing vs administrative processes; Software quality assurance document inspections; map software quality assurance requirements document; failure mode effects analysis for requirements document; measuring the right response variables; and questions.

  9. Incorporating Six Sigma Methodology Training into Chemical Engineering Education

    ERIC Educational Resources Information Center

    Dai, Lenore L.

    2007-01-01

    Six Sigma is a buzz term in today's technology and business world and there has been increasing interest to initiate Six Sigma training in college education. We have successfully incorporated Six Sigma methodology training into a traditional chemical engineering course, Engineering Experimentation, at Texas Tech University. The students have…

  10. The crystal structure of the anti-σ factor CnrY in complex with the σ factor CnrH shows a new structural class of anti-σ factors targeting extracytoplasmic function σ factors.

    PubMed

    Maillard, Antoine P; Girard, Eric; Ziani, Widade; Petit-Härtlein, Isabelle; Kahn, Richard; Covès, Jacques

    2014-06-12

    Gene expression in bacteria is regulated at the level of transcription initiation, a process driven by σ factors. The regulation of σ factor activity proceeds from the regulation of their cytoplasmic availability, which relies on specific inhibitory proteins called anti-σ factors. With anti-σ factors regulating their availability according to diverse cues, extracytoplasmic function σ factors (σ(ECF)) form a major signal transduction system in bacteria. Here, structure:function relationships have been characterized in an emerging class of minimal-size transmembrane anti-σ factors, using CnrY from Cupriavidus metallidurans CH34 as a model. This study reports the 1.75-Å-resolution structure of CnrY cytosolic domain in complex with CnrH, its cognate σ(ECF), and identifies a small hydrophobic knob in CnrY as the major determinant of this interaction in vivo. Unsuspected structural similarity with the molecular switch regulating the general stress response in α-proteobacteria unravels a new class of anti-σ factors targeting σ(ECF). Members of this class carry out their function via a 30-residue stretch that displays helical propensity but no canonical structure on its own. PMID:24727125

  11. A structural model of anti-anti-[sigma];#963; inhibition by a two-component receiver domain: the PhyR stress response regulator

    SciTech Connect

    Herrou, Julien; Foreman, Robert; Fiebig, Aretha; Crosson, Sean

    2012-03-30

    PhyR is a hybrid stress regulator conserved in {alpha}-proteobacteria that contains an N-terminal {sigma}-like (SL) domain and a C-terminal receiver domain. Phosphorylation of the receiver domain is known to promote binding of the SL domain to an anti-{sigma} factor. PhyR thus functions as an anti-anti-{sigma} factor in its phosphorylated state. We present genetic evidence that Caulobacter crescentus PhyR is a phosphorylation-dependent stress regulator that functions in the same pathway as {sigma}{sup T} and its anti-{sigma} factor, NepR. Additionally, we report the X-ray crystal structure of PhyR at 1.25 {angstrom} resolution, which provides insight into the mechanism of anti-anti-{sigma} regulation. Direct intramolecular contact between the PhyR receiver and SL domains spans regions {sigma}{sub 2} and {sigma}{sub 4}, likely serving to stabilize the SL domain in a closed conformation. The molecular surface of the receiver domain contacting the SL domain is the structural equivalent of {alpha}4-{beta}5-{alpha}5, which is known to undergo dynamic conformational change upon phosphorylation in a diverse range of receiver proteins. We propose a structural model of PhyR regulation in which receiver phosphorylation destabilizes the intramolecular interaction between SL and receiver domains, thereby permitting regions {sigma}{sub 2} and {sigma}{sub 4} in the SL domain to open about a flexible connector loop and bind anti-{sigma} factor.

  12. Non-compact nonlinear sigma models

    NASA Astrophysics Data System (ADS)

    de Rham, Claudia; Tolley, Andrew J.; Zhou, Shuang-Yong

    2016-09-01

    The target space of a nonlinear sigma model is usually required to be positive definite to avoid ghosts. We introduce a unique class of nonlinear sigma models where the target space metric has a Lorentzian signature, thus the associated group being non-compact. We show that the would-be ghost associated with the negative direction is fully projected out by 2 second-class constraints, and there exist stable solutions in this class of models. This result also has important implications for Lorentz-invariant massive gravity: There exist stable nontrivial vacua in massive gravity that are free from any linear vDVZ-discontinuity and a Λ2 decoupling limit can be defined on these vacua.

  13. Pharmacology and therapeutic potential of sigma(1) receptor ligands.

    PubMed

    Cobos, E J; Entrena, J M; Nieto, F R; Cendán, C M; Del Pozo, E

    2008-12-01

    Sigma (sigma) receptors, initially described as a subtype of opioid receptors, are now considered unique receptors. Pharmacological studies have distinguished two types of sigma receptors, termed sigma(1) and sigma(2). Of these two subtypes, the sigma(1) receptor has been cloned in humans and rodents, and its amino acid sequence shows no homology with other mammalian proteins. Several psychoactive drugs show high to moderate affinity for sigma(1) receptors, including the antipsychotic haloperidol, the antidepressant drugs fluvoxamine and sertraline, and the psychostimulants cocaine and methamphetamine; in addition, the anticonvulsant drug phenytoin allosterically modulates sigma(1) receptors. Certain neurosteroids are known to interact with sigma(1) receptors, and have been proposed to be their endogenous ligands. These receptors are located in the plasma membrane and in subcellular membranes, particularly in the endoplasmic reticulum, where they play a modulatory role in intracellular Ca(2+) signaling. Sigma(1) receptors also play a modulatory role in the activity of some ion channels and in several neurotransmitter systems, mainly in glutamatergic neurotransmission. In accordance with their widespread modulatory role, sigma(1) receptor ligands have been proposed to be useful in several therapeutic fields such as amnesic and cognitive deficits, depression and anxiety, schizophrenia, analgesia, and against some effects of drugs of abuse (such as cocaine and methamphetamine). In this review we provide an overview of the present knowledge of sigma(1) receptors, focussing on sigma(1) ligand neuropharmacology and the role of sigma(1) receptors in behavioral animal studies, which have contributed greatly to the potential therapeutic applications of sigma(1) ligands. PMID:19587856

  14. Phantom black holes and sigma models

    SciTech Connect

    Azreg-Aienou, Mustapha; Clement, Gerard; Fabris, Julio C.; Rodrigues, Manuel E.

    2011-06-15

    We construct static multicenter solutions of phantom Einstein-Maxwell-dilaton theory from null geodesics of the target space, leading to regular black holes without spatial symmetry for certain discrete values of the dilaton coupling constant. We also discuss the three-dimensional gravitating sigma models obtained by reduction of phantom Einstein-Maxwell, phantom Kaluza-Klein and phantom Einstein-Maxwell-dilaton-axion theories. In each case, we generate by group transformations phantom charged black hole solutions from a neutral seed.

  15. Strangeness and meson-nucleon sigma terms

    SciTech Connect

    Dahiya, Harleen; Sharma, Neetika

    2011-10-21

    The chiral constituent quark model ({chi}CQM) has been extended to calculate the flavor structure of the nucleon through the meson-nucleon sigma terms which have large contributions from the quark sea and are greatly affected by chiral symmetry breaking and SU(3) symmetry breaking. The hidden strangeness component in the nucleon has also been investigated and its significant contribution is found to be consistent with the recent available experimental observations.

  16. Production of the SIGMA(0)(C) and SIGMA(++)(C) by High Energy Neutrons.

    NASA Astrophysics Data System (ADS)

    Ladbury, Raymond Llewellyn, Jr.

    We present the first observation of hadroproduction of the Sigma_sp{c}{++ } and Sigma_sp{c }{0}, decaying into Lambda _{c}pi. The daughter Lambda_{c} is observed in the decay modes pKpi and pK _{s}pipi. The Experiment was conducted at a broadband neutron beam in the Proton East area of the Fermi National Accelerator Laboratory. A two-magnet multiparticle spectrometer equipped with proportional wire chambers and a high resolution MWPC vertex detector was used to momentum analyze charged particles produced in the interactions of neutrons on targets of beryllium, silicon and tungsten. Particles were identified using three Cerenkov counters. The beam energy for each event was reconstructed using hadronic and electromagnetic calorimetry. The mass differences delta m_ {Sigma_sp{c}{++}- Lambda_{c}}, delta m_{Sigma_sp{c }{0}-Lambda_{c}} and delta m_{Sigma _sp{c}{++}-Sigma_sp {c}{0}} are measured and found to be 166.4 +/-.3 +/- 2.0 MeV/c^2, 178.5 +/-.3 +/- 2.5MeV/c ^2 and -12.1 +/- .4 +/- 2.8MeV/c^2 . This last value is larger in magnitude than the predictions of most theoretical calculations. We also report measurements of particle to antiparticle ratios, x_{f} dependence, A dependence, and p_{t} dependence of the production cross sections. The total production cross sections of the Sigma_sp{c} {0} and Sigma_sp {c}{++} are calculated, assuming {dsigmaover dx_{f }} ~ (1 -x)^4, linear atomic weight dependence, B(Lambda_{c} to pKpi) =.022, and symmetric production of particle and antiparticle. From this, and the value of sigma cdot B( Lambda_{c} to pK_sp{s}{0} pipi), calculated under the same assumptions, we calculate the ratio of branching fractions {B(Lambda_{c} to p| K^{0}pipi)}over {B(Lambda_{c}to pKpi) }. We conclude that the level of charm production indicated by our measurements is substantially higher than that predicted by first order gluon-gluon fusion.

  17. Improving Quality of Seal Leak Test Product using Six Sigma

    NASA Astrophysics Data System (ADS)

    Luthfi Malik, Abdullah; Akbar, Muhammad; Irianto, Dradjad

    2016-02-01

    Seal leak test part is a polyurethane material-based product. Based on past data, defect level of this product was 8%, higher than the target of 5%. Quality improvement effort was done using six sigma method that included phases of define, measure, analyse, improve, and control. In the design phase, a Delphi method was used to identify factors that were critical to quality. In the measure phase, stability and process capability was measured. Fault tree analysis (FTA) and failure mode and effect analysis (FMEA) were used in the next phase to analize the root cause and to determine the priority issues. Improve phase was done by compiling, selecting, and designing alternative repair. Some improvement efforts were identified, i.e. (i) making a checklist for maintenance schedules, (ii) making written reminder form, (iii) modifying the SOP more detail, and (iv) performing a major service to the vacuum machine. To ensure the continuity of improvement efforts, some control activities were executed, i.e. (i) controlling, monitoring, documenting, and setting target frequently, (ii) implementing reward and punishment system, (iii) adding cleaning tool, and (iv) building six sigma organizational structure.

  18. {Sigma}{sub b,c} to Nucleon Transitions in Light Cone QCD Sum Rules

    SciTech Connect

    Bayar, M.; Azizi, K.; Zeyrek, M. T.

    2011-05-23

    The loop level flavor changing neutral current transitions of the {Sigma}{sub b}{yields}nl{sup +}l{sup -} and {Sigma}{sub c}{yields}pl{sup +}l{sup -} are investigated in the light cone QCD sum rules approach. Using the most general form of the interpolating current for {Sigma}{sub Q}, Q = b or c, the transition form factors are calculated using two sets of input parameters entering the nucleon distribution amplitudes, namely, QCD sum rules and lattice QCD inputs. The obtained results are used to estimate the decay rates of the corresponding transitions. Since such type transitions occurred at loop level in the standard model, they can be considered as good candidates to search for the new physics effects beyond the SM.

  19. Electron-Impact Excitation of the B ^1SIGMA^+, C^1SIGMA^+ and E^1PI States of

    NASA Technical Reports Server (NTRS)

    Kanik, I.; Ratliff, M.; Trajmar, S.

    1993-01-01

    Electron impact excitation of CO plays an important role in planetary atmospheres andinterstellar clouds. At the present time, serious discrepancies exist among excitation cross sectionsreported in the literature for this molecule. We measured electron impact excitation cross sections forB^1SIGMA^+right arrowX^1SIGMA^+, C^1SIGMA^+right arrowX^1SIGMA^+ and E^1PIrightarrowX^1SIGMA^+ states of CO at 100eV impact energy using electron energy-loss spectroscopy.

  20. Allosteric modulation of sigma-1 receptors by SKF83959 inhibits microglia-mediated inflammation.

    PubMed

    Wu, Zhuang; Li, Linlang; Zheng, Long-Tai; Xu, Zhihong; Guo, Lin; Zhen, Xuechu

    2015-09-01

    Recent studies have shown that sigma-1 receptor orthodox agonists can inhibit neuroinflammation. SKF83959 (3-methyl-6-chloro-7,8-hydroxy-1-[3-methylphenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine), an atypical dopamine receptor-1 agonist, has been recently identified as a potent allosteric modulator of sigma-1 receptor. Here, we investigated the anti-inflammatory effects of SKF83959 in lipopolysaccharide (LPS)-stimulated BV2 microglia. Our results indicated that SKF83959 significantly suppressed the expression/release of the pro-inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), and inhibited the generation of reactive oxygen species. All of these responses were blocked by selective sigma-1 receptor antagonists (BD1047 or BD1063) and by ketoconazole (an inhibitor of enzyme cytochrome c17 to inhibit the synthesis of endogenous dehydroepiandrosterone, DHEA). Additionally, we found that SKF83959 promoted the binding activity of DHEA with sigma-1 receptors, and enhanced the inhibitory effects of DHEA on LPS-induced microglia activation in a synergic manner. Furthermore, in a microglia-conditioned media system, SKF83959 inhibited the cytotoxicity of conditioned medium generated by LPS-activated microglia toward HT-22 neuroblastoma cells. Taken together, our study provides the first evidence that allosteric modulation of sigma-1 receptors by SKF83959 inhibits microglia-mediated inflammation. SKF83959 is a potent allosteric modulator of sigma-1 receptor. Our results indicated that SKF83959 enhanced the activity of endogenous dehydroepiandrosterone (DHEA) in a synergic manner, and inhibited the activation of BV2 microglia and the expression/release of the pro-inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS). PMID:26031312

  1. Transcription of two sigma 70 homologue genes, sigA and sigB, in stationary-phase Mycobacterium tuberculosis.

    PubMed

    Hu, Y; Coates, A R

    1999-01-01

    The sigA and sigB genes of Mycobacterium tuberculosis encode two sigma 70-like sigma factors of RNA polymerase. While transcription of the sigA gene is growth rate independent, sigB transcription is increased during entry into stationary phase. The sigA gene transcription is unresponsive to environmental stress but that of sigB is very responsive, more so in stationary-phase growth than in log-phase cultures. These data suggest that SigA is a primary sigma factor which, like sigma70, controls the transcription of the housekeeping type of promoters. In contrast, SigB, although showing some overlap in function with SigA, is more like the alternative sigma factor, sigmaS, which controls the transcription of the gearbox type of promoters. Primer extension analysis identified the RNA start sites for both genes as 129 nucleotides upstream to the GTG start codon of sigA and 27 nucleotides from the ATG start codon of sigB. The -10 promoter of sigA but not that of sigB was similar to the sigma70 promoter. The half-life of the sigA transcript was very long, and this is likely to play an important part in its regulation. In contrast, the half-life of the sigB transcript was short, about 2 min. These results demonstrate that the sigB gene may control the regulons of stationary phase and general stress resistance, while sigA may be involved in the housekeeping regulons. PMID:9882660

  2. Mechanistic Implications of the Unique Structural Features and Dimerization of the Cytoplasmic Domain of the Pseudomonas Sigma Regulator, PupR

    SciTech Connect

    Jensen, Jaime L.; Balbo, Andrea; Neau, David B.; Chakravarthy, Srinivas; Zhao, Huaying; Sinha, Sangita C.; Colbert, Christopher L.

    2015-09-29

    Gram-negative bacteria tightly regulate intracellular levels of iron, an essential nutrient. To ensure this tight regulation, some outer membrane TonB-dependent transporters (TBDTs) that are responsible for iron import stimulate their own transcription in response to extracellular binding by an iron-laden siderophore. This process is mediated by an inner membrane sigma regulator protein (an anti-sigma factor) that transduces an unknown periplasmic signal from the TBDT to release an intracellular sigma factor from the inner membrane, which ultimately upregulates TBDT transcription. Here we use the Pseudomonas putida ferric-pseudobactin BN7/BN8 sigma regulator, PupR, as a model system to understand the molecular mechanism of this conserved class of sigma regulators. We have determined the X-ray crystal structure of the cytoplasmic anti-sigma domain (ASD) of PupR to 2.0 Å. Size exclusion chromatography, small angle X-ray scattering, and sedimentation velocity analytical ultracentrifugation, all indicate that in contrast to other ASDs, the PupR-ASD exists as a dimer in solution. Mutagenesis of residues at the dimer interface identified from the crystal structure disrupts dimerization and protein stability, as determined by sedimentation velocity analytical ultracentrifugation and thermal denaturation circular dichroism spectroscopy. Lastly, these combined results suggest that this type of inner membrane sigma regulator may utilize an unusual mechanism to sequester their cognate sigma factors and prevent transcription activation.

  3. Mechanistic Implications of the Unique Structural Features and Dimerization of the Cytoplasmic Domain of the Pseudomonas Sigma Regulator, PupR

    DOE PAGESBeta

    Jensen, Jaime L.; Balbo, Andrea; Neau, David B.; Chakravarthy, Srinivas; Zhao, Huaying; Sinha, Sangita C.; Colbert, Christopher L.

    2015-09-29

    Gram-negative bacteria tightly regulate intracellular levels of iron, an essential nutrient. To ensure this tight regulation, some outer membrane TonB-dependent transporters (TBDTs) that are responsible for iron import stimulate their own transcription in response to extracellular binding by an iron-laden siderophore. This process is mediated by an inner membrane sigma regulator protein (an anti-sigma factor) that transduces an unknown periplasmic signal from the TBDT to release an intracellular sigma factor from the inner membrane, which ultimately upregulates TBDT transcription. Here we use the Pseudomonas putida ferric-pseudobactin BN7/BN8 sigma regulator, PupR, as a model system to understand the molecular mechanism ofmore » this conserved class of sigma regulators. We have determined the X-ray crystal structure of the cytoplasmic anti-sigma domain (ASD) of PupR to 2.0 Å. Size exclusion chromatography, small angle X-ray scattering, and sedimentation velocity analytical ultracentrifugation, all indicate that in contrast to other ASDs, the PupR-ASD exists as a dimer in solution. Mutagenesis of residues at the dimer interface identified from the crystal structure disrupts dimerization and protein stability, as determined by sedimentation velocity analytical ultracentrifugation and thermal denaturation circular dichroism spectroscopy. Lastly, these combined results suggest that this type of inner membrane sigma regulator may utilize an unusual mechanism to sequester their cognate sigma factors and prevent transcription activation.« less

  4. Mechanistic Implications of the Unique Structural Features and Dimerization of the Cytoplasmic Domain of the Pseudomonas Sigma Regulator, PupR.

    PubMed

    Jensen, Jaime L; Balbo, Andrea; Neau, David B; Chakravarthy, Srinivas; Zhao, Huaying; Sinha, Sangita C; Colbert, Christopher L

    2015-09-29

    Gram-negative bacteria tightly regulate intracellular levels of iron, an essential nutrient. To ensure this strict control, some outer membrane TonB-dependent transporters (TBDTs) that are responsible for iron import stimulate their own transcription in response to extracellular binding by an iron-laden siderophore. This process is mediated by an inner membrane sigma regulator protein (an anti-sigma factor) that transduces an unknown periplasmic signal from the TBDT to release an intracellular sigma factor from the inner membrane, which ultimately upregulates TBDT transcription. Here, we use the Pseudomonas putida ferric-pseudobactin BN7/BN8 sigma regulator, PupR, as a model system to understand the molecular mechanism of this conserved class of sigma regulators. We have determined the X-ray crystal structure of the cytoplasmic anti-sigma domain (ASD) of PupR to 2.0 Å. Size exclusion chromatography, small-angle X-ray scattering, and sedimentation velocity analytical ultracentrifugation all indicate that, in contrast to other ASDs, the PupR-ASD exists as a dimer in solution. Mutagenesis of residues at the dimer interface identified from the crystal structure disrupts dimerization and protein stability, as determined by sedimentation velocity analytical ultracentrifugation and thermal denaturation circular dichroism spectroscopy. These combined results suggest that this type of inner membrane sigma regulator may utilize an unusual mechanism to sequester their cognate sigma factors and prevent transcription activation. PMID:26313375

  5. Sigma meson and lowest possible glueball candidate in an extended linear {sigma} model

    SciTech Connect

    Mukherjee, Tamal K.; Huang Mei; Yan Qishu

    2012-10-23

    We formulate an extended linear {sigma} model of a quarkonia nonet and a tetraquark nonet as well as a complex iso-singlet (glueball) field to study the low-lying scalar meson. Chiral symmetry and U{sub A}(1) symmetry and their breaking play important role to shape the scalar meson spectrum in our work. Based on our study we will comment on what may be the mass of the lowest possible scalar and pseudoscalar glueball states. We will also discuss on what may be the nature of the sigma or f{sub 0}(600) meson.

  6. Different intracellular distribution of avian reovirus core protein sigmaA in cells of avian and mammalian origin

    SciTech Connect

    Vazquez-Iglesias, Lorena; Lostale-Seijo, Irene; Martinez-Costas, Jose; Benavente, Javier

    2012-10-25

    A comparative analysis of the intracellular distribution of avian reovirus (ARV) core protein sigmaA in cells of avian and mammalian origin revealed that, whereas the viral protein accumulates in the cytoplasm and nucleolus of avian cells, most sigmaA concentrates in the nucleoplasm of mammalian cells in tight association with the insoluble nuclear matrix fraction. Our results further showed that sigmaA becomes arrested in the nucleoplasm of mammalian cells via association with mammalian cell-specific factors and that this association prevents nucleolar targeting. Inhibition of RNA polymerase II activity, but not of RNA polymerase I activity, in infected mammalian cells induces nucleus-to-cytoplasm sigmaA translocation through a CRM1- and RanGTP-dependent mechanism, yet a heterokaryon assay suggests that sigmaA does not shuttle between the nucleus and cytoplasm. The scarcity of sigmaA in cytoplasmic viral factories of infected mammalian cells could be one of the factors contributing to limited ARV replication in mammalian cells.

  7. Sigma model BPS lumps on a torus

    NASA Astrophysics Data System (ADS)

    Nakamula, Atsushi; Sasaki, Shin

    2012-09-01

    We study doubly periodic Bogomol’nyi-Prasad-Sommerfield lumps in supersymmetric CPN-1 nonlinear sigma models on a torus T2. Following the philosophy of the Harrington-Shepard construction of calorons in Yang-Mills theory, we obtain the n-lump solutions on compact spaces by suitably arranging the n lumps on R2 at equal intervals. We examine the modular invariance of the solutions and find that there are no modular invariant solutions for n=1, 2 in this construction.

  8. Lambda and Sigma photoproduction on the neutron

    SciTech Connect

    P. Nadel-Turonski; B. L. Berman

    2006-06-01

    The gamma n --> K^0_s Y and gamma n --> K^+Sigma^-(1385) channels are being analyzed using the CLAS g10 data set. As recent calculations show a large sensitivity of, e.g., the proposed D_13(1900) resonance to polarization observables, we hope to extend this study by making a new experiment with polarized real photon beams and an LD_2 target in CLAS, to measure all gamma(pol) n --> K(pol)Y reactions. N* decays to low-lying KY* and K*Y states, as well as Y(pol)-N final state interactions would also be investigated.

  9. Properties of the sigma meson at finite temperature

    NASA Astrophysics Data System (ADS)

    Ibarra, J. R. Morones; Aguirre, A. J. Garza; Flores-Baez, Francisco V.

    2015-12-01

    We study the changes of the mass and width of the sigma meson in the framework of the Linear Sigma Model at finite temperature, in the one-loop approximation. We have found that as the temperature increases, the mass of sigma shifts down. We have also analyzed the σ-spectral function and we observe an enhancement at the threshold which is a signature of partial restoration of chiral symmetry, also interpreted as a tendency to chiral phase transition. Additionally, we studied the width of the sigma, when the threshold enhancement takes place, for different values of the sigma mass. We found that there is a brief enlargement followed by an abrupt fall in the width as the temperature increases, which is also related with the restoration of chiral symmetry and an indication that the sigma is a bound state of two pions.

  10. Formation sigma measurement from thermal neutron detection

    SciTech Connect

    Albats, P.; Hertzog, R.C.; Mahdavi, M.

    1993-08-10

    In a logging system including a sonde for traversing a borehole at a controlled speed between spaced apart elevations in an earth formation, means carried by the sonde for irradiating the formation and generating detector signals indicative of the response of the borehole environment in and around the sonde to the radiation, and data processing means for computing at least one characteristic of the borehole environment from the detector signals, said at least one characteristic including the macroscopic thermal absorption cross section of the formation (formation sigma), the logging method is described using said sonde comprising the steps of: (a) irradiating the formation with a pulsed source of high energy neutrons as the sonde traverses the borehole, whereby the neutrons generated at each pulse interact with the borehole environment to produce a neutron population having a space, time and energy distribution including epithermal and thermal energies; (b) with a detector that has an azimuthally limited angle of receptivity, detecting the time-dependent population of thermal neutrons at an eccentric position in the borehole during a period of time between successive source pulses and generating a thermal neutron detector signal commensurate with said time-dependent population; and (c) from the thermal neutron detector signal, computing the value of formation sigma at the elevation of said eccentric position.

  11. Ionic rotational branching ratios in resonant enhanced multiphoton ionization of NO via the A2Sigma(+)(3s sigma) and D2Sigma(+)(3p sigma) states

    NASA Technical Reports Server (NTRS)

    Rudolph, H.; Mckoy, V.; Dixit, S. N.; Huo, W. M.

    1988-01-01

    Results are presented for the rotationally resolved photoelectron spectra resulting from a (2 + 1) one-color resonant enhanced multiphoton ionization (REMPI) of NO via the rotationally clean S21(11.5) and mixed S11(15.5) + R21(15.5) branches of the 0-0 transition in the D-X band. The calculations were done in the fixed-nuclei frozen core approximation. The resulting photoionization spectra, convoluted with a Lorentzian detection function, agree qualitatively with experimental results of Viswanathan et al. (1986) and support their conclusion that the nonspherical nature of the molecular potential creates a substantial l-mixing in the continuum, which in turn leads to the intense Delta N = 0 peak. The rather strong photoelectron energy dependence of the rotational branching ratios of the D 2Sigma(+) S21(11.5) line was investigated and compared to the weak energy dependence of the A 2Sigma(+) R22(21.5) line.

  12. g{sub {Sigma}{sub Q{Sigma}{sub Q{pi}}}}coupling constant via light cone QCD sum rules

    SciTech Connect

    Azizi, K.; Bayar, M.; Ozpineci, A.; Sarac, Y.

    2010-10-01

    Using the most general form of the interpolating currents, the coupling constants g{sub {Sigma}{sub b{Sigma}{sub b{pi}}}}and g{sub {Sigma}{sub c{Sigma}{sub c{pi}}}}are calculated within the light cone QCD sum rules approach. It is found that g{sub {Sigma}{sub c{Sigma}{sub c{pi}=}}}-8.0{+-}1.7 and g{sub {Sigma}{sub b{Sigma}{sub b{pi}=}}}-11.0{+-}2.1.

  13. Mucosal vaccination by adenoviruses displaying reovirus sigma 1

    SciTech Connect

    Weaver, Eric A.; Camacho, Zenaido T.; Hillestad, Matthew L.; Crosby, Catherine M.; Turner, Mallory A.; Guenzel, Adam J.; Fadel, Hind J.; Mercier, George T.; Barry, Michael A.

    2015-08-15

    We developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but has 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generates stronger T cell responses than Ad5 when used for mucosal immunization. In this work, new Ad5-fiber-sigma vectors were generated by varying the number of fiber β-spiral shaft repeats (R) between the fiber tail and sigma. Increasing chimera length led to decreasing insertion of these proteinsAd5 virions. Ad-R3 and R14 vectors effectively targeted JAM-1 in vitro while R20 did not. When wereused to immunize mice by the intranasal route, Ad5-R3-sigma produced higher serum and vaginal antibody responses than Ad5. These data suggest optimized Ad-sigma vectors may be useful vectors for mucosal vaccination. - Highlights: • Constructed adenoviruses (Ads) displaying different reovirus sigma 1 fusion proteins. • Progressively longer chimeras were more poorly encapsidated onto Ad virions. • Ad5-R3-sigma mediated better systemic and mucosal immune responses than Ad5.

  14. Prediction of three sigma maximum dispersed density for aerospace applications

    NASA Technical Reports Server (NTRS)

    Charles, Terri L.; Nitschke, Michael D.

    1993-01-01

    Free molecular heating (FMH) is caused by the transfer of energy during collisions between the upper atmosphere molecules and a space vehicle. The dispersed free molecular heating on a surface is an important constraint for space vehicle thermal analyses since it can be a significant source of heating. To reduce FMH to a spacecraft, the parking orbit is often designed to a higher altitude at the expense of payload capability. Dispersed FMH is a function of both space vehicle velocity and atmospheric density, however, the space vehicle velocity variations are insignificant when compared to the atmospheric density variations. The density of the upper atmosphere molecules is a function of altitude, but also varies with other environmental factors, such as solar activity, geomagnetic activity, location, and time. A method has been developed to predict three sigma maximum dispersed density for up to 15 years into the future. This method uses a state-of-the-art atmospheric density code, MSIS 86, along with 50 years of solar data, NASA and NOAA solar activity predictions for the next 15 years, and an Aerospace Corporation correlation to account for density code inaccuracies to generate dispersed maximum density ratios denoted as 'K-factors'. The calculated K-factors can be used on a mission unique basis to calculate dispersed density, and hence dispersed free molecular heating rates. These more accurate K-factors can allow lower parking orbit altitudes, resulting in increased payload capability.

  15. Efficacy of fuzzy MADM approach in Six Sigma analysis phase in automotive sector

    NASA Astrophysics Data System (ADS)

    Rathi, Rajeev; Khanduja, Dinesh; Sharma, S. K.

    2016-02-01

    Six Sigma is a strategy for achieving process improvement and operational excellence within an organization. Decisions on critical parameter selection in analysis phase are always very crucial; it plays a primary role in successful execution of Six Sigma project and for productivity improvement in manufacturing environment and involves the imprecise, vague and uncertain information. Using a case study approach; the paper demonstrates a tactical approach for selection of critical factors of machine breakdown in center less grinding (CLG) section at an automotive industry using fuzzy logic based multi attribute decision making approach. In this context, we have considered six crucial attributes for selection of critical factors for breakdown. Mean time between failure is found to be the pivotal selection criterion in CLG section. Having calculated the weights pertinent to criteria through two methods (fuzzy VIKOR and fuzzy TOPSIS) critical factors for breakdown are prioritized. Our results are in strong agreement with the perceptions of production and maintenance department of the company.

  16. The Activity of σV, an Extracytoplasmic Function σ Factor of Bacillus subtilis, Is Controlled by Regulated Proteolysis of the Anti-σ Factor RsiV

    PubMed Central

    Hastie, Jessica L.; Williams, Kyle B.

    2013-01-01

    During growth in the environment, bacteria encounter stresses which can delay or inhibit their growth. To defend against these stresses, bacteria induce both resistance and repair mechanisms. Many bacteria regulate these resistance mechanisms using a group of alternative σ factors called extracytoplasmic function (ECF) σ factors. ECF σ factors represent the largest and most diverse family of σ factors. Here, we demonstrate that the activation of a member of the ECF30 subfamily of ECF σ factors, σV in Bacillus subtilis, is controlled by the proteolytic destruction of the anti-σ factor RsiV. We will demonstrate that the degradation of RsiV and, thus, the activation of σV requires multiple proteolytic steps. Upon exposure to the inducer lysozyme, the extracellular domain of RsiV is removed by an unknown protease, which cleaves at site 1. This cleavage is independent of PrsW, the B. subtilis site 1 protease, which cleaves the anti-σ factor RsiW. Following cleavage by the unknown protease, the N-terminal portion of RsiV requires further processing, which requires the site 2 intramembrane protease RasP. Our data indicate that the N-terminal portion of RsiV from amino acid 1 to 60, which lacks the extracellular domain, is constitutively degraded unless RasP is absent, indicating that RasP cleavage is constitutive. This suggests that the regulatory step in RsiV degradation and, thus, σV activation are controlled at the level of the site 1 cleavage. Finally, we provide evidence that increased resistance to lysozyme decreases σV activation. Collectively, these data provide evidence that the mechanism for σV activation in B. subtilis is controlled by regulated intramembrane proteolysis (RIP) and requires the site 2 protease RasP. PMID:23687273

  17. Characterization of pulmonary sigma receptors by radioligand binding

    PubMed Central

    Lever, John R.; Litton, Tyler P.; Fergason-Cantrell, Emily A.

    2015-01-01

    This study establishes the expression of appreciable populations of sites on mouse lung membranes that exhibit radioligand binding properties and pharmacology consistent with assignment as sigma1 and sigma2 receptors. Specific binding of the sigma1 receptor radioligand [3H](+)-pentazocine reached steady state within 6 h at 37 °C. Saturation studies revealed high affinity binding to a single class of sites (Kd 1.36 ± 0.04 nM; Bmax 967 ± 11 fmol / mg protein). Inhibition studies showed appropriate sigma1 receptor pharmacology, including higher affinity for (+)-N-allylnormetazocine with respect to the (−)-enantiomer, and positive allosteric modulation of dextromethorphan binding by phenytoin. Using [3H]1,3-di(2-tolyl)guanidine in the presence of (+)-pentazocine to assess sigma2 receptor binding, steady state was achieved within 2 min at 25 °C. Cold saturation studies revealed one high affinity, low capacity binding site (Kd 31.8 ± 8.3 nM; Bmax 921 ± 228 fmol / mg protein) that displayed sigma2 receptor pharmacology. A very low affinity, high capacity interaction also was observed that represents saturable, but not sigma receptor specific, binding. A panel of ligands showed rank order inhibition of radioligand binding appropriate for the sigma2 receptor, with ifenprodil displaying the highest apparent affinity. In vivo, dextromethorphan inhibited the specific binding of a radioiodinated sigma1 receptor ligand in lung with an ED50 of 1.2 µmol / kg, a value near the recommended dosage for the drug as a cough suppressant. Overall, the present work provides a foundation for studies of drug interactions with pulmonary sigma1 and sigma2 receptors in vitro and in vivo. PMID:26004528

  18. Characterization of pulmonary sigma receptors by radioligand binding.

    PubMed

    Lever, John R; Litton, Tyler P; Fergason-Cantrell, Emily A

    2015-09-01

    This study establishes the expression of appreciable populations of sites on mouse lung membranes that exhibit radioligand binding properties and pharmacology consistent with assignment as sigma1 and sigma2 receptors. Specific binding of the sigma1 receptor radioligand [(3)H](+)-pentazocine reached steady state within 6h at 37°C. Saturation studies revealed high affinity binding to a single class of sites (Kd 1.36±0.04nM; Bmax 967±11fmol/mg protein). Inhibition studies showed appropriate sigma1 receptor pharmacology, including higher affinity for (+)-N-allylnormetazocine with respect to the (-)-enantiomer, and positive allosteric modulation of dextromethorphan binding by phenytoin. Using [(3)H]1,3-di(2-tolyl)guanidine in the presence of (+)-pentazocine to assess sigma2 receptor binding, steady state was achieved within 2min at 25°C. Cold saturation studies revealed one high affinity, low capacity binding site (Kd 31.8±8.3nM; Bmax 921±228fmol/mg protein) that displayed sigma2 receptor pharmacology. A very low affinity, high capacity interaction also was observed that represents saturable, but not sigma receptor specific, binding. A panel of ligands showed rank order inhibition of radioligand binding appropriate for the sigma2 receptor, with ifenprodil displaying the highest apparent affinity. In vivo, dextromethorphan inhibited the specific binding of a radioiodinated sigma1 receptor ligand in lung with an ED50 of 1.2μmol/kg, a value near the recommended dosage for the drug as a cough suppressant. Overall, the present work provides a foundation for studies of drug interactions with pulmonary sigma1 and sigma2 receptors in vitro and in vivo. PMID:26004528

  19. In silico analysis and molecular modeling of RNA polymerase, sigma S (RpoS) protein in Pseudomonas aeruginosa PAO1

    PubMed Central

    Sedighi, Mansour; Moghoofei, Mohsen; Kouhsari, Ebrahim; Pournajaf, Abazar; Emadi, Behzad; Tohidfar, Masoud; Gholami, Mehrdad

    2015-01-01

    Background: Sigma factors are proteins that regulate transcription in bacteria. Sigma factors can be activated in response to different environmental conditions. The rpoS (RNA polymerase, sigma S) gene encodes sigma-38 (σ38, or RpoS), a 37.8 kDa protein in Pseudomonas aeruginosa (P. aeruginosa) strains. RpoS is a central regulator of the general stress response and operates in both retroactive and proactive manners; not only does it allow the cell to survive environmental challenges; it also prepares the cell for subsequent stresses (cross-protection). Methods: The significance of RpoS for stress resistance and protein expression in stationary-phase P. aeruginosa cells was assessed. The goal of the current study was to characterize RpoS of P. aeruginosa PAO1 using bioinformatics tools. Results: The results showed that RpoS is an unstable protein that belongs to the sigma-70 factor family. Secondary structure analysis predicted that random coil is the predominant structure followed by extended alpha helix. The three-dimensional (3D) structure was modeled using SWISS-MODEL Workspace. Conclusion: Determination of sequence, function, structure, and predicted epitopes of RpoS is important for modeling of inhibitors that will help in the design of new drugs to combat multi-drug-resistant (MDR) strains. Such information may aid in the development of new diagnostic tools, drugs, and vaccines for treatment in endemic regions. PMID:26989748

  20. [Improvement of medical processes with Six Sigma - practicable zero-defect quality in preparation for surgery].

    PubMed

    Sobottka, Stephan B; Töpfer, Armin; Eberlein-Gonska, Maria; Schackert, Gabriele; Albrecht, D Michael

    2010-01-01

    Six Sigma is an innovative management- approach to reach practicable zero- defect quality in medical service processes. The Six Sigma principle utilizes strategies, which are based on quantitative measurements and which seek to optimize processes, limit deviations or dispersion from the target process. Hence, Six Sigma aims to eliminate errors or quality problems of all kinds. A pilot project to optimize the preparation for neurosurgery could now show that the Six Sigma method enhanced patient safety in medical care, while at the same time disturbances in the hospital processes and failure costs could be avoided. All six defined safety relevant quality indicators were significantly improved by changes in the workflow by using a standardized process- and patient- oriented approach. Certain defined quality standards such as a 100% complete surgical preparation at start of surgery and the required initial contact of the surgeon with the patient/ surgical record on the eve of surgery could be fulfilled within the range of practical zero- defect quality. Likewise, the degree of completion of the surgical record by 4 p.m. on the eve of surgery and their quality could be improved by a factor of 170 and 16, respectively, at sigma values of 4.43 and 4.38. The other two safety quality indicators "non-communicated changes in the OR- schedule" and the "completeness of the OR- schedule by 12:30 a.m. on the day before surgery" also show an impressive improvement by a factor of 2.8 and 7.7, respectively, corresponding with sigma values of 3.34 and 3.51. The results of this pilot project demonstrate that the Six Sigma method is eminently suitable for improving quality of medical processes. In our experience this methodology is suitable, even for complex clinical processes with a variety of stakeholders. In particular, in processes in which patient safety plays a key role, the objective of achieving a zero- defect quality is reasonable and should definitely be aspirated. PMID

  1. Environmental Data Flow Six Sigma Process Improvement Savings Overview

    SciTech Connect

    Paige, Karen S

    2015-05-20

    An overview of the Environmental Data Flow Six Sigma improvement project covers LANL’s environmental data processing following receipt from the analytical laboratories. The Six Sigma project identified thirty-three process improvements, many of which focused on cutting costs or reducing the time it took to deliver data to clients.

  2. Application of Six Sigma Method to EMS Design

    NASA Astrophysics Data System (ADS)

    Rusko, Miroslav; Králiková, Ružena

    2011-01-01

    The Six Sigma method is a complex and flexible system of achieving, maintaining and maximizing the business success. Six Sigma is based mainly on understanding the customer needs and expectation, disciplined use of facts and statistics analysis, and responsible approach to managing, improving and establishing new business, manufacturing and service processes.

  3. delta. sigma/sub L//(pp) and jet physics

    SciTech Connect

    Richards, D.G.

    1988-01-01

    We show that there is a positive contribution to ..delta..sigma/sub L/(pp; s) = sigma /sub tot/(p(+)p(+); s) /minus/ sigma/sub tot/(p(+)p(/minus/); s) (where the +- refer to proton helicities) associated with the pointlike scattering of fundamental constituents. Simple arguments imply that this positive contribution would, at very high s, be larger in absolute value than the negative contribution to ..delta..sigma/sub L/ predicted from the exchange of the A/sub 1/ reggeon, and furthermore may provide important insight into the shape of the spin weighted quark and gluon distributions. Measurements of ..delta..sigma/sub L/ in the energy range ..sqrt..s = 18 /minus/ 30 GeV also should help clarify theoretical ideas associated with the observations of ''minijets'' and could aid in the prediction of event structure at future high energy colliders. 24 refs. 6 figs.

  4. Automated system for measurement, collection and processing of hydrometeorological data aboard scientific research vessels of the GUGMS (SIGMA-s)

    NASA Technical Reports Server (NTRS)

    Borisenkov, Y. P.; Fedorov, O. M.

    1974-01-01

    A report is made on the automated system known as SIGMA-s for the measurement, collection, and processing of hydrometeorological data aboard scientific research vessels of the Hydrometeorological Service. The various components of the system and the interfacing between them are described, as well as the projects that the system is equipped to handle.

  5. A comparison of regional isentropic-sigma and sigma model simulations of the January 1979 Chicago blizzard

    NASA Technical Reports Server (NTRS)

    Zapotocny, Tom H.; Johnson, Donald R.; Reames, Fred M.

    1993-01-01

    In an initial effort in regional numerical weather prediction, results from the University of Wisconsin isentropic-sigma (UW theta-sigma) hybrid model and an 'identical' sigma model are compared. The two main objectives are to demonstrate the capability of the UW theta-sigma model for regional numerical weather prediction and to identify advantages of the hybrid model in simulating atmospheric water vapor transport and precipitation relative to the sigma model. The 72-h simulations produced by the two models extend over a region covering the western Pacific Ocean, North America, and the western Atlantic Ocean. The simulations begin at 0000 UTC 13 January 1979, a period during which an intense Chicago blizzard develops over the central United States. This period also includes the rapid development of a cyclone in the western Pacific Ocean. Results using the Global Weather Experiment (GWE) ECMWF level IIIB data as initial and verification data indicate that both models produce reasonable and similar 72-h simulations, with the UW theta-sigma model mass and momentum distributions being slightly more accurate than the sigma model. Of particular importance for the Chicago blizzard is that the UW theta-sigma model more accurately simulates water vapor transport northward from the Gulf of Mexico and westward from the Atlantic Ocean. As a result, the hybrid model more accurately simulates observed precipitation, especially over the northeastern U.S. and southeastern Canada.

  6. Differential regulation of type III secretion and virulence genes in Bordetella pertussis and Bordetella bronchiseptica by a secreted anti-σ factor

    PubMed Central

    Ahuja, Umesh; Shokeen, Bhumika; Cheng, Ning; Cho, Yeonjoo; Blum, Charles; Coppola, Giovanni; Miller, Jeff F.

    2016-01-01

    The BvgAS phosphorelay regulates ∼10% of the annotated genomes of Bordetella pertussis and Bordetella bronchiseptica and controls their infectious cycles. The hierarchical organization of the regulatory network allows the integration of contextual signals to control all or specific subsets of BvgAS-regulated genes. Here, we characterize a regulatory node involving a type III secretion system (T3SS)-exported protein, BtrA, and demonstrate its role in determining fundamental differences in T3SS phenotypes among Bordetella species. We show that BtrA binds and antagonizes BtrS, a BvgAS-regulated extracytoplasmic function (ECF) sigma factor, to couple the secretory activity of the T3SS apparatus to gene expression. In B. bronchiseptica, a remarkable spectrum of expression states can be resolved by manipulating btrA, encompassing over 80 BtrA-activated loci that include genes encoding toxins, adhesins, and other cell surface proteins, and over 200 BtrA-repressed genes that encode T3SS apparatus components, secretion substrates, the BteA effector, and numerous additional factors. In B. pertussis, BtrA retains activity as a BtrS antagonist and exerts tight negative control over T3SS genes. Most importantly, deletion of btrA in B. pertussis revealed T3SS-mediated, BteA-dependent cytotoxicity, which had previously eluded detection. This effect was observed in laboratory strains and in clinical isolates from a recent California pertussis epidemic. We propose that the BtrA-BtrS regulatory node determines subspecies-specific differences in T3SS expression among Bordetella species and that B. pertussis is capable of expressing a full range of T3SS-dependent phenotypes in the presence of appropriate contextual cues. PMID:26884180

  7. AtSIG6 and other members of the sigma gene family jointly but differentially determine plastid target gene expression in Arabidopsis thaliana.

    PubMed

    Bock, Sylvia; Ortelt, Jennifer; Link, Gerhard

    2014-01-01

    Plants contain a nuclear gene family for plastid sigma factors, i.e., proteins that associate with the "bacterial-type" organellar RNA polymerase and confer the ability for correct promoter binding and transcription initiation. Questions that are still unresolved relate to the "division of labor" among members of the sigma family, both in terms of their range of target genes and their temporal and spatial activity during development. Clues to the in vivo role of individual sigma genes have mainly come from studies of sigma knockout lines. Despite its obvious strengths, however, this strategy does not necessarily trace-down causal relationships between mutant phenotype and a single sigma gene, if other family members act in a redundant and/or compensatory manner. We made efforts to reduce the complexity by genetic crosses of Arabidopsis single mutants (with focus on a chlorophyll-deficient sig6 line) to generate double knockout lines. The latter typically had a similar visible phenotype as the parental lines, but tended to be more strongly affected in the transcript patterns of both plastid and sigma genes. Because triple mutants were lethal under our growth conditions, we exploited a strategy of transformation of single and double mutants with RNAi constructs that contained sequences from the unconserved sigma region (UCR). These RNAi/knockout lines phenotypically resembled their parental lines, but were even more strongly affected in their plastid transcript patterns. Expression patterns of sigma genes revealed both similarities and differences compared to the parental lines, with transcripts at reduced or unchanged amounts and others that were found to be present in higher (perhaps compensatory) amounts. Together, our results reveal considerable flexibility of gene activity at the levels of both sigma and plastid gene expression. A (still viable) "basal state" seems to be reached, if 2-3 of the 6 Arabidopsis sigma genes are functionally compromised. PMID:25505479

  8. Dipole moments and transition probabilities of the i 3Pi sub g-b 3Sigma(+) sub u, c 3Pi sub u-a 3Sigma(+) sub g, and i 3Pi sub g-c 3Pi sub u systems of molecular hydrogen

    NASA Technical Reports Server (NTRS)

    Guberman, Steven L.; Dalgarno, A.

    1992-01-01

    Bonn-Oppenheimer-based ab initio calculations of dipole moments from the i 3Pi sub g-b 3Sigma(+) sub u, c 3Pi sub u-a 3Sigma(+) sub g, and i 3Pi sub g-c 3Pi sub u transitions of H2 have been conducted, to yield a tabulation of the dipole transition probabilities and Franck-Condon factors. These factors are given for transitions originating in the lowest vibrational level of the ground X 1Sigma(+) sub g state.

  9. An Application of Six Sigma to Reduce Supplier Quality Cost

    NASA Astrophysics Data System (ADS)

    Gaikwad, Lokpriya Mohanrao; Teli, Shivagond Nagappa; Majali, Vijay Shashikant; Bhushi, Umesh Mahadevappa

    2016-01-01

    This article presents an application of Six Sigma to reduce supplier quality cost in manufacturing industry. Although there is a wider acceptance of Six Sigma in many organizations today, there is still a lack of in-depth case study of Six Sigma. For the present research the case study methodology was used. The company decided to reduce quality cost and improve selected processes using Six Sigma methodologies. Regarding the fact that there is a lack of case studies dealing with Six Sigma especially in individual manufacturing organization this article could be of great importance also for the practitioners. This paper discusses the quality and productivity improvement in a supplier enterprise through a case study. The paper deals with an application of Six Sigma define-measure-analyze-improve-control methodology in an industry which provides a framework to identify, quantify and eliminate sources of variation in an operational process in question, to optimize the operation variables, improve and sustain performance viz. process yield with well-executed control plans. Six Sigma improves the process performance (process yield) of the critical operational process, leading to better utilization of resources, decreases variations and maintains consistent quality of the process output.

  10. Neuroprotective effects of high affinity sigma 1 receptor selective compounds

    PubMed Central

    Luedtke, Robert R.; Perez, Evelyn; Yang, Shao-Hua; Liu, Ran; Vangveravong, Suwanna; Tu, Zhude; Mach, Robert H.; Simpkins, James W.

    2014-01-01

    We previously reported that the antipsychotic drug haloperidol, a multifunctional D2-like dopamine and sigma receptor subtype antagonist, has neuroprotective properties. In this study we further examined the association between neuroprotection and receptor antagonism by evaluating a panel of novel compounds with varying affinity at sigma and D2-like dopamine receptors. These compounds were evaluated using an in vitro cytotoxicity assay that utilizes a hippocampal-derived cell line, HT-22, in the presence or absence of varying concentrations (5 to 20 mM) of glutamate. While haloperidol was found to be a potent neuroprotective agent in this in vitro cell assay, the prototypic sigma 1 receptor agonist (+)-pentazocine was found not to be neuroprotective. Subsequently, the potency for the neuroprotection of HT-22 cells was evaluated for a) three SV series indoles which have nMolar affinity at D2-like receptors but varying affinity at sigma 1 receptor and b) two benzyl phenylacetamides sigma 1 receptor selective compounds which bind with low affinity at D2-like receptors but have nMolar affinity for the sigma 1 receptor. We observed that cytoprotection correlated with the affinity of the compounds for sigma 1 receptors. Based upon results from the HT-22 cell-based in vitro assay, two phenylacetamides, LS-127 and LS-137, were further evaluated in vivo using a transient middle cerebral artery occlusion (t-MCAO) model of stroke. At a dose of 100 µg/kg, both LS-127 and LS-137 attenuated infarct volume by approximately 50%. These studies provide further evidence that sigma 1 receptor selective compounds can provide neuroprotection in cytotoxic situations. These results also demonstrate that sigma 1 receptor selective benzyl phenylacetamides are candidate pharmacotherapeutic agents that could be used to minimize neuronal death after a stroke or head trauma. PMID:22285434

  11. The sigma model on complex projective superspaces

    NASA Astrophysics Data System (ADS)

    Candu, Constantin; Mitev, Vladimir; Quella, Thomas; Saleur, Hubert; Schomerus, Volker

    2010-02-01

    The sigma model on projective superspaces mathbb{C}{mathbb{P}^{S - 1left| S right.}} gives rise to a continuous family of interacting 2D conformal field theories which are parametrized by the curvature radius R and the theta angle θ. Our main goal is to determine the spectrum of the model, non-perturbatively as a function of both parameters. We succeed to do so for all open boundary conditions preserving the full global symmetry of the model. In string theory parlor, these correspond to volume filling branes that are equipped with a monopole line bundle and connection. The paper consists of two parts. In the first part, we approach the problem within the continuum formulation. Combining combinatorial arguments with perturbative studies and some simple free field calculations, we determine a closed formula for the partition function of the theory. This is then tested numerically in the second part. There we extend the proposal of [ arXiv:0908.1081 ] for a spin chain regularization of the mathbb{C}{mathbb{P}^{S - 1left| S right.}} model with open boundary conditions and use it to determine the spectrum at the conformal fixed point. The numerical results are in remarkable agreement with the continuum analysis.

  12. Sigma: Web Retrieval Interface for Nuclear Reaction Data

    SciTech Connect

    Pritychenko,B.; Sonzogni, A.A.

    2008-06-24

    The authors present Sigma, a Web-rich application which provides user-friendly access in processing and plotting of the evaluated and experimental nuclear reaction data stored in the ENDF-6 and EXFOR formats. The main interface includes browsing using a periodic table and a directory tree, basic and advanced search capabilities, interactive plots of cross sections, angular distributions and spectra, comparisons between evaluated and experimental data, computations between different cross section sets. Interactive energy-angle, neutron cross section uncertainties plots and visualization of covariance matrices are under development. Sigma is publicly available at the National Nuclear Data Center website at www.nndc.bnl.gov/sigma.

  13. Nucleon sigma term and quark condensate in nuclear matter

    SciTech Connect

    K. Tsushima; K. Saito; A. W. Thomas; A. Valcarce

    2007-03-01

    We study the bound nucleon sigma term and its effect on the quark condensate in nuclear matter. In the quark-meson coupling (QMC) model it is shown that the nuclear correction to the sigma term is small and negative. Thus, the correction decelerates the decrease of the quark condensate in nuclear matter. However, the quark condensate in nuclear matter is controlled primarily by the scalar-isoscalar sigma field of the model. It appreciably moderates the decrease relative to the leading term at densities around and larger than the normal nuclear matter density.

  14. Structural and biophysical studies on two promoter recognition domains of the extra-cytoplasmic function σ factor σC from Mycobacterium tuberculosis

    PubMed Central

    Thakur, Krishan Gopal; Joshi, Anagha Madhusudan; Gopal, B.

    2007-01-01

    Summary σ factors are transcriptional regulatory proteins that bind to the RNA polymerase and dictate gene expression. The extracytoplasmic function σ factors (ECF) govern the environment dependent regulation of transcription. ECF σ factors have two domains σ2 and σ4 that recognize the −10 and −35 promoter elements. However, unlike the primary σ factor σA, the ECF σ factors lack σ3, a region that helps in the recognition of the extended −10 element and σ1.1, a domain involved in the auto-inhibition of σA in the absence of core RNA polymerase. Mycobacterium tuberculosis σC is an ECF σ factor that is essential for the pathogenesis and virulence of M. tuberculosis in the mouse and guinea pig models of infection. However, unlike other ECF σ factors, σC does not appear to have a regulatory anti-σ factor located in the same operon. We also note that Mycobacterium tuberculosis σC differs from the canonical ECF σ factors as it has an N-terminal domain comprising of 126 amino acids that precedes the σC2 and σC4 domains. In an effort to understand the regulatory mechanism of this protein, the crystal structures of the σC2 and σC4 domains of σC were determined. These promoter recognition domains are structurally similar to the corresponding domains of σA despite the low sequence similarity. Fluorescence experiments using the intrinsic tryptophan residues of σC2 as well as surface plasmon resonance measurements reveal that the σC2 and σC4 domains interact with each other. Mutational analysis suggests that the Pribnow box binding region of σC2 is involved in this inter-domain interaction. Interaction between the promoter recognition domains in M. tuberculosis σC are thus likely to regulate the activity of this protein even in the absence of an anti-σ factor. PMID:17145760

  15. Influence of general stress-response alternative sigma factors σ(S) (RpoS) and σ(B) (SigB) on bacterial tolerance to the essential oils from Origanum vulgare L. and Rosmarinus officinalis L. and pulsed electric fields.

    PubMed

    Gomes Neto, Nelson Justino; Magnani, Marciane; Chueca, Beatriz; García-Gonzalo, Diego; Pagán, Rafael; de Souza, Evandro Leite

    2015-10-15

    This study assessed the influence of general stress-response alternative sigma factors RpoS (σ(S)) and SigB (σ(B)) on tolerance of Escherichia coli (E. coli MG1655 and its isogenic mutant E. coli MG1655 ΔrpoS) and Listeria monocytogenes (L. monocytogenes EGD-e and its isogenic mutant L. monocytogenes EGD-e ΔsigB) to the essential oils (EOs) from Origanum vulgare L.-oregano (OVEO) and Rosmarinus officinalis L.-rosemary (ROEO), as well as the changes in tolerance of parental and ΔrpoS and ΔsigB mutant strains to OVEO, ROEO and pulsed electric fields (PEF) following overnight exposure to subinhibitory concentrations (1/2×minimum inhibitory concentration-MIC) of each tested EO. MIC values of OVEO and ROEO against the mutant cells were usually lower than those found against the parental cells. Survivor curves showed that mutant cells were more sensitive to these EOs than parental cells. The recovery of survivors in selective media showed a greater proportion of cells sublethally injured at their cell envelopes in the mutant strains compared with the parental strains. Induction of increased direct-tolerance to OVEO and ROEO or cross-tolerance to PEF was not observed after pre-exposure of parental and mutant cells to EOs. Otherwise, parental and mutant cells of E. coli and L. monocytogenes pre-exposed to OVEO or ROEO showed decreased tolerance when further treated with the homologous stressing agent at 2×MIC. Still, mutant cells pre-exposed to OVEO or ROEO showed lower tolerance to PEF than parental strains. These results showed the influence of σ(S) and σ(B) in tolerance of single strains of E. coli and L. monocytogenes, respectively, to OVEO and ROEO. Moreover, the deletion of σ(S) and σ(B) resulted in decreased tolerance to OVEO, ROEO or PEF in tested strains following exposure to OVEO or ROEO at a subinhibitory concentration. PMID:26159473

  16. Transcription factor-based biosensor

    SciTech Connect

    Dietrich, Jeffrey A; Keasling, Jay D

    2013-10-08

    The present invention provides for a system comprising a BmoR transcription factor, a .sigma..sup.54-RNA polymerase, and a pBMO promoter operatively linked to a reporter gene, wherein the pBMO promoter is capable of expression of the reporter gene with an activated form of the BmoR and the .sigma..sup.54-RNA polymerase.

  17. Novel sigmaB regulation modules of Gram-positive bacteria involve the use of complex hybrid histidine kinases.

    PubMed

    de Been, Mark; Francke, Christof; Siezen, Roland J; Abee, Tjakko

    2011-01-01

    A common bacterial strategy to cope with stressful conditions is the activation of alternative sigma factors that control specific regulons enabling targeted responses. In the human pathogen Bacillus cereus, activation of the major stress-responsive sigma factor σ(B) is controlled by a signalling route that involves the multi-sensor hybrid histidine kinase RsbK. RsbK-type kinases are not restricted to the B. cereus group, but occur in a wide variety of other bacterial species, including members of the the low-GC Gram-positive genera Geobacillus and Paenibacillus as well as the high-GC actinobacteria. Genome context and protein sequence analyses of 118 RsbK homologues revealed extreme variability in N-terminal sensory as well as C-terminal regulatory domains and suggested that RsbK-type kinases are subject to complex fine-tuning systems, including sensitization and desensitization via methylation and demethylation within the helical domain preceding the H-box. The RsbK-mediated stress-responsive sigma factor activation mechanism that has evolved in B. cereus and the other species differs markedly from the extensively studied and highly conserved RsbRST-mediated σ(B) activation route found in Bacillus subtilis and other low-GC Gram-positive bacteria. Implications for future research on sigma factor control mechanisms are presented and current knowledge gaps are briefly discussed. PMID:21051490

  18. Dilatonic non-linear sigma models and Ricci flow extensions

    NASA Astrophysics Data System (ADS)

    Carfora, M.; Marzuoli, A.

    2016-09-01

    We review our recent work describing, in terms of the Wasserstein geometry over the space of probability measures, the embedding of the Ricci flow in the renormalization group flow for dilatonic non-linear sigma models.

  19. The Six Sigma initiative at Mount Sinai Medical Center.

    PubMed

    Chassin, Robert

    2008-01-01

    Lean Six Sigma, in various forms, has been used widely in many Fortune 500 companies. Motorola, General Electric, Sony, American Express, and Bechtel all use Six Sigma to improve quality and performance. While the impact of this methodology has been documented extensively by the press in manufacturing and transactional settings, less evidence is available regarding its utility in health care environments. Mount Sinai Medical Center initiated a Six Sigma program in 2000 to determine its applicability and value in a large academic medical center. This article discusses Mount Sinai Medical Center's experience adapting this methodology to improve both patient care and business processes and outcomes. We present an overview of Six Sigma, and offer examples of projects undertaken using this data-driven approach to performance improvement. Lastly, the article provides insights and lessons learned regarding this organization-wide experience. PMID:18306249

  20. POLARIMETRIC OBSERVATIONS OF {sigma} ORIONIS E

    SciTech Connect

    Carciofi, A. C.; Faes, D. M.; Townsend, R. H. D.; Bjorkman, J. E.

    2013-03-20

    Some massive stars possess strong magnetic fields that confine plasma in the circumstellar environment. These magnetospheres have been studied spectroscopically, photometrically, and, more recently, interferometrically. Here we report on the first firm detection of a magnetosphere in continuum linear polarization, as a result of monitoring {sigma} Ori E at the Pico dos Dias Observatory. The non-zero intrinsic polarization indicates an asymmetric structure whose minor elongation axis is oriented 150. Degree-Sign 0 east of the celestial north. A modulation of the polarization was observed with a period of half of the rotation period, which supports the theoretical prediction of the presence of two diametrally opposed, corotating blobs of gas. A phase lag of -0.085 was detected between the polarization minimum and the primary minimum of the light curve, suggestive of a complex shape of the plasma clouds. We present a preliminary analysis of the data with the Rigidly Rotating Magnetosphere model, which could not reproduce simultaneously the photometric and polarimetric data. A toy model comprising two spherical corotating blobs joined by a thin disk proved more successful in reproducing the polarization modulation. With this model we were able to determine that the total scattering mass of the thin disk is similar to the mass of the blobs (2M{sub b}/M{sub d} = 1.2) and that the blobs are rotating counterclockwise on the plane of the sky. This result shows that polarimetry can provide a diagnostic of the geometry of clouds, which will serve as an important constraint for improving the Rigidly Rotating Magnetosphere model.

  1. A role for interaction of the RNA polymerase flap domain with the sigma subunit in promoter recognition.

    PubMed

    Kuznedelov, Konstantin; Minakhin, Leonid; Niedziela-Majka, Anita; Dove, Simon L; Rogulja, Dragana; Nickels, Bryce E; Hochschild, Ann; Heyduk, Tomasz; Severinov, Konstantin

    2002-02-01

    In bacteria, promoter recognition depends on the RNA polymerase sigma subunit, which combines with the catalytically proficient RNA polymerase core to form the holoenzyme. The major class of bacterial promoters is defined by two conserved elements (the -10 and -35 elements, which are 10 and 35 nucleotides upstream of the initiation point, respectively) that are contacted by sigma in the holoenzyme. We show that recognition of promoters of this class depends on the "flexible flap" domain of the RNA polymerase beta subunit. The flap interacts with conserved region 4 of sigma and triggers a conformational change that moves region 4 into the correct position for interaction with the -35 element. Because the flexible flap is evolutionarily conserved, this domain may facilitate promoter recognition by specificity factors in eukaryotes as well. PMID:11823642

  2. Milestone Report - M31SW030904 - Sigma Team Coordination Meeting

    SciTech Connect

    Jubin, Robert Thomas

    2010-11-24

    This documents the completion of the FCR&D Level 3 milestone for the Off-Gas Sigma Team - ORNL work package (FTOR11SW0309), “Sigma Team Coordination Meeting” (M31SW030904), due 30 November 10. The subject meeting was held at Idaho National Laboratory on October 12 and 13, 2010. The agenda and meeting minutes are attached to this memo.

  3. Lean sigma--will it work for healthcare?

    PubMed

    Bahensky, James A; Roe, Janet; Bolton, Romy

    2005-01-01

    The manufacturing industry has been using Lean Sigma for years in pursuit of continuous improvement to obtain a competitive advantage. The objectives of these efforts are to use the Lean techniques for reducing cycle times and the Six Sigma concepts for reducing product defects. The Iowa Business Council with several advocates worked with the University of Iowa Hospital and Clinics (UIHC) and two other Iowa hospitals to determine whether Lean Sigma is adaptable in healthcare. A team of 15 people at UIHC used the Kaizen Breakthrough Methodology over a five-day period in an aggressive identification and elimination of non-value added activities in Radiology CT scanning. The results exceeded the initial project objectives and indicated that Lean Sigma is applicable in healthcare. Overall, the Lean Sigma project increased revenue by approximately $750,000 per year. The Kaizen process proved to be successful and interesting. Within three days, the team installed new work flow processes. This implementation-oriented approach is what differentiates Lean Sigma from other quality improvement processes. PMID:15682675

  4. Sigma-delta cellular neural network for 2D modulation.

    PubMed

    Aomori, Hisashi; Otake, Tsuyoshi; Takahashi, Nobuaki; Tanaka, Mamoru

    2008-01-01

    Although sigma-delta modulation is widely used for analog-to-digital (A/D) converters, sigma-delta concepts are only for 1D signals. Signal processing in the digital domain is extremely useful for 2D signals such as used in image processing, medical imaging, ultrasound imaging, and so on. The intricate task that provides true 2D sigma-delta modulation is feasible in the spatial domain sigma-delta modulation using the discrete-time cellular neural network (DT-CNN) with a C-template. In the proposed architecture, the A-template is used for a digital-to-analog converter (DAC), the C-template works as an integrator, and the nonlinear output function is used for the bilevel output. In addition, due to the cellular neural network (CNN) characteristics, each pixel of an image corresponds to a cell of a CNN, and each cell is connected spatially by the A-template. Therefore, the proposed system can be thought of as a very large-scale and super-parallel sigma-delta modulator. Moreover, the spatio-temporal dynamics is designed to obtain an optimal reconstruction signal. The experimental results show the excellent reconstruction performance and capabilities of the CNN as a sigma-delta modulator. PMID:18215502

  5. Sigma model Q-balls and Q-stars

    SciTech Connect

    Verbin, Y.

    2007-10-15

    A new kind of Q-balls is found: Q-balls in a nonlinear sigma model. Their main properties are presented together with those of their self-gravitating generalization, sigma model Q-stars. A simple special limit of solutions which are bound by gravity alone ('sigma stars') is also discussed briefly. The analysis is based on calculating the mass, global U(1) charge and binding energy for families of solutions parametrized by the central value of the scalar field. Two kinds (differing by the potential term) of the new sigma model Q-balls and Q-stars are analyzed. They are found to share some characteristics while differing in other respects like their properties for weak central scalar fields which depend strongly on the form of the potential term. They are also compared with their ordinary counterparts and although similar in some respects, significant differences are found like the existence of an upper bound on the central scalar field. A special subset of the sigma model Q-stars contains those which do not possess a flat space limit. Their relation with sigma star solutions is discussed.

  6. A prototypical Sigma-1 receptor antagonist protects against brain ischemia

    PubMed Central

    Schetz, John A.; Perez, Evelyn; Liu, Ran; Chen, Shiuhwei; Lee, Ivan; Simpkins, James W.

    2016-01-01

    Previous studies indicate that the Sigma-1 ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) protects the brain from ischemia. Less clear is whether protection is mediated by agonism or antagonism of the Sigma-1 receptor, and whether drugs already in use for other indications and that interact with the Sigma-1 receptor might also prevent oxidative damage due to conditions such as cerebral ischemic stroke. The antipsychotic drug haloperidol is an antagonist of Sigma-1 receptors and in this study it potently protects against oxidative stress-related cell death in vitro at low concentrations. The protective potency of haloperidol and a number of other butyrophenone compounds positively correlate with their affinity for a cloned Sigma-1 receptor, and the protection is mimicked by a Sigma-1 receptor-selective antagonist (BD1063), but not an agonist (PRE-084). In vivo, an acute low dose (0.05 mg/kg s.c.) of haloperidol reduces by half the ischemic lesion volume induced by a transient middle cerebral artery occlusion. These in vitro and in vivo pre-clinical results suggest that a low dose of acutely administered haloperidol might have a novel application as a protective agent against ischemic cerebral stroke and other types of brain injury with an ischemic component. PMID:17919467

  7. Reovirus polypeptide sigma 3 and N-terminal myristoylation of polypeptide mu 1 are required for site-specific cleavage to mu 1C in transfected cells.

    PubMed Central

    Tillotson, L; Shatkin, A J

    1992-01-01

    N-myristoylated viral polypeptide mu 1 was produced in COS cells transfected with a transient expression vector containing a DNA copy of the reovirus M2 gene. The mu 1 product was specifically cleaved to polypeptide mu 1C in cells that were cotransfected with the reovirus S4 gene and that expressed polypeptide sigma 3. Studies with site-specific mutants of the M2 gene demonstrated that conversion of mu 1 to mu 1C was dependent on myristoylation and the presence of the proteolytic cleavage sequence asparagine 42-proline 43 in mu 1, as well as on the presence of polypeptide sigma 3. The mu 1C product and polypeptide sigma 3 formed complexes that were immunoprecipitated by sigma 3-directed antibody, and a myristoylation-negative M2 double mutant, G2A-N42T, yielded mu 1 that did not undergo cleavage to mu 1C or bind sigma 3. However, the N42T single mutant did form immunoprecipitable complexes with sigma 3, indicating that binding can occur in the absence of cleavage. Polypeptide sigma 3 alternatively can bind double-stranded RNA and in COS cells stimulates translation of reporter chloramphenicol acetyltransferase mRNA translation, presumably by blocking double-stranded RNA-mediated activation of the eukaryotic initiation factor 2 alpha subunit kinase which inhibits the initiation of protein synthesis. Consistent with these observations and with the formation of mu 1C-sigma 3 complexes, coexpression of M2 with S4 DNA prevented the translational stimulatory effect of polypeptide sigma 3. Images PMID:1548757

  8. The energy dependence of the pp {yields} K{sup +}n{Sigma}{sup +} reaction

    SciTech Connect

    Valdau, Yu.

    2011-10-24

    The energy dependence of the total cross section for the pp {yields} K{sup +}n{Sigma}{sup +} reaction has been investigated at the magnetic spectrometer COSY-ANKE. Signals from the production of the {Sigma}{sup +} hyperon were searched for in three simultaneously measured spectra. The values obtained for the total production cross section {sigma}({Sigma}{sup +}) are slightly below those of {sigma}({Sigma}{sup 0}) at the same excess energies. They follow a phase space dependence and do not show any evidence for strong threshold effects or a significant n{Sigma}{sup +} final state interaction.

  9. Pyoverdine and beyond: PvdS dependent gene regulation in Pseudomonas syringae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The extracytoplasmic function (ECF) sigma factor PvdS regulates the expression of genes in Pseudomonas aeruginosa encoding virulence factors and the biosynthesis and transport of pyoverdine, a siderophore involved in iron acquisition. The production of pyoverdine is a distinctive trait of the fluor...

  10. Interaction of new antidepressants with sigma-1 receptor chaperones and their potentiation of neurite outgrowth in PC12 cells.

    PubMed

    Ishima, Tamaki; Fujita, Yuko; Hashimoto, Kenji

    2014-03-15

    The sigma-1 receptor chaperone located in the endoplasmic reticulum (ER) may be implicated in the mechanistic action of some antidepressants. The present study was undertaken to examine whether new antidepressant drugs interact with the sigma-1 receptor chaperone. First, we examined the effects of selective serotonin reuptake inhibitors (SSRIs) (fluvoxamine, paroxetine, sertraline, citalopram and escitalopram), serotonin and noradrenaline reuptake inhibitors (SNRIs) (duloxetine, venlafaxine, milnacipran), and mirtazapine, a noradrenaline and specific serotonergic antidepressant (NaSSA), on [(3)H](+)-pentazocine binding to rat brain membranes. Then, we examined the effects of these drugs on nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. The order of potency for drugs at the sigma-1 receptor chaperone was as follows: fluvoxamine>sertraline>fluoxetine>escitalopram>citalopram>paroxetine>duoxetine. Venlafaxine, milnacipran, and mirtazapine showed very weak affinity for this chaperone. Furthermore, fluvoxamine, fluoxetine, escitalopram, and mirtazapine significantly potentiated NGF-induced neurite outgrowth in cell assays, and the effects of all these drugs, excluding mirtazapine, were antagonized by NE-100, a selective antagonist of the sigma-1 receptor chaperone. Moreover, the effects of fluvoxamine and fluoxetine on neurite outgrowth were also antagonized by sertraline, indicating that sertraline may be an antagonist at the sigma-1 receptor chaperone. The effect of mirtazapine on neurite outgrowth was antagonized by the selective 5-hydroxytryptamine1A receptor antagonist WAY-100635. These findings suggest that activation at the sigma-1 receptor chaperone may be involved in the action of some SSRIs, such as fluvoxamine, fluoxetine and escitalopram. In contrast, mirtazapine independently potentiated neurite outgrowth in PC12 cells, indicating that this beneficial effect may mediate its pharmacological effect. PMID:24508523

  11. Distinct binding sites for zinc and double-stranded RNA in the reovirus outer capsid protein sigma3

    SciTech Connect

    Schiff, L.A.; Nibert, M.L.; Co, M.S.; Brown, E.G.; Fields, B.N.

    1988-01-01

    By atomic absorption analysis, the authors determined that the reovirus outer capsid protein sigma3, which binds double-stranded RNA (dsRNA), is a zinc metalloprotein. Using Northwestern blots and a novel zinc blotting technique, the authors localized the zinc- and dsRNA-binding activities of sigma3 to distinct V8 protease-generated fragments. Zinc-binding activity was contained within an amino-terminal fragment that contained a transcription factor IIIA-like zinc-binding sequence, and dsRNA-binding activity was associated with a carboxy-terminal fragment. By these techniques, new zinc- and dsRNA-binding activities were also detected in reovirus core proteins. A sequence similarity was observed between the catalytic site of the picornavirus proteases and the transcription factor IIIA-like zinc-binding site within sigma3. The authors suggest that the zinc- and dsRNA-binding activities of sigma3 may be important for its proposed regulatory effects on viral and host cell transcription and translation.

  12. OBSERVATIONAL SELECTION EFFECTS AND THE M-{sigma} RELATION

    SciTech Connect

    Gueltekin, Kayhan; Richstone, Douglas O.; Tremaine, Scott; Loeb, Abraham

    2011-09-01

    We examine the possibility that the observed relation between black hole mass and host-galaxy stellar velocity dispersion (the M-{sigma} relation) is biased by an observational selection effect, the difficulty of detecting a black hole whose sphere of influence is smaller than the telescope resolution. In particular, we critically investigate recent claims that the M-{sigma} relation only represents the upper limit to a broad distribution of black hole masses in galaxies of a given velocity dispersion. We find that this hypothesis can be rejected at a high confidence level, at least for the early-type galaxies with relatively high velocity dispersions (median 268 km s{sup -1}) that comprise most of our sample. We also describe a general procedure for incorporating observational selection effects in estimates of the properties of the M-{sigma} relation. Applying this procedure we find results that are consistent with earlier estimates that did not account for selection effects, although with larger error bars. In particular, (1) the width of the M-{sigma} relation is not significantly increased, (2) the slope and normalization of the M-{sigma} relation are not significantly changed, and (3) most or all luminous early-type galaxies contain central black holes at zero redshift. Our results may not apply to late-type or small galaxies, which are not well represented in our sample.

  13. Photoproduction of the Sigma(1385) resonance at LEPS

    NASA Astrophysics Data System (ADS)

    Hicks, Kenneth

    2008-04-01

    The Sigma(1385) hyperon resonance has been measured using the LEPS detector at the SPring-8 facility in Japan. Linearly polarized photons in the range of 1.5-2.4 GeV were incident on a liquid deuterium target, producing a K^+ and a &-circ; in the final state. The negative Sigma(1385) was isolated by its decay to (λ&-circ;) using the missing mass technique. The same final state particles can also used to identify photoproduction of the &-circ; ground state via its decay to (n&-circ;). Using simulations to correct for the detector acceptance, it will be possible to link the cross sections for the Sigma(1385) to the previously measured cross sections for photoproduction of K^+&-circ;. Theoretical calculations for photoproduction of K^+&*-circ; from the neutron are in progress, and will be discussed along with the data analysis of this reaction.

  14. Reduction of MPEG ringing artifacts using adaptive sigma filter

    NASA Astrophysics Data System (ADS)

    Pan, Hao

    2006-01-01

    In this paper, we propose a novel computationally efficient post-processing algorithm to reduce ringing artifacts in the decoded DCT-coded video without using coding information. While the proposed algorithm is based on edge information as most filtering-based de-ringing algorithms do, this algorithm solely uses one single computationally efficient nonlinear filter, namely sigma filter, for both edge detection and smoothing. Specifically, the sigma filter, which was originally designed for nonlinear filtering, is extended to generate edge proximity information. Different from other adaptive filtering-based methods, whose filters typically use a fixed small window but flexible weights, this sigma filter adaptively switches between small and large windows. The adaptation is designed for removing ringing artifacts only, so the algorithm cannot be used for de-blocking. Overall, the proposed algorithm achieves a good balance among removing ringing artifacts, preserving edges and details, and computational complexity.

  15. sigma model approach to the heterotic string theory

    SciTech Connect

    Sen, A.

    1985-09-01

    Relation between the equations of motion for the massless fields in the heterotic string theory, and the conformal invariance of the sigma model describing the propagation of the heterotic string in arbitrary background massless fields is discussed. It is emphasized that this sigma model contains complete information about the string theory. Finally, we discuss the extension of the Hull-Witten proof of local gauge and Lorentz invariance of the sigma-model to higher order in ..cap alpha..', and the modification of the transformation laws of the antisymmetric tensor field under these symmetries. Presence of anomaly in the naive N = 1/2 supersymmetry transformation is also pointed out in this context. 12 refs.

  16. SigmaCLIPSE = presentation management + NASA CLI PS + SQL

    NASA Technical Reports Server (NTRS)

    Weiss, Bernard P., Jr.

    1990-01-01

    SigmaCLIPSE provides an expert systems and 'intelligent' data base development program for diverse systems integration environments that require support for automated reasoning and expert systems technology, presentation management, and access to 'intelligent' SQL data bases. The SigmaCLIPSE technology and and its integrated ability to access 4th generation application development and decision support tools through a portable SQL interface, comprises a sophisticated software development environment for solving knowledge engineering and expert systems development problems in information intensive commercial environments -- financial services, health care, and distributed process control -- where the expert system must be extendable -- a major architectural advantage of NASA CLIPS. SigmaCLIPSE is a research effort intended to test the viability of merging SQL data bases with expert systems technology.

  17. Double soft theorems and shift symmetry in nonlinear sigma models

    NASA Astrophysics Data System (ADS)

    Low, Ian

    2016-02-01

    We show that both the leading and subleading double soft theorems of the nonlinear sigma model follow from a shift symmetry enforcing Adler's zero condition in the presence of an unbroken global symmetry. They do not depend on the underlying coset G /H and are universal infrared behaviors of Nambu-Goldstone bosons. Although nonlinear sigma models contain an infinite number of interaction vertices, the double soft limit is determined entirely by a single four-point interaction, together with the existence of Adler's zeros.

  18. THE STORY OF SIGMA HYPERNUCLEI - A MODERN FABLE.

    SciTech Connect

    CHRIEN,R.E.

    1999-02-19

    The reality of {Sigma} hypernuclei has been the subject of intense concern among experimenters and theoreticians for more than 20 years. The possible existence of {Sigma} hypernuclei was first suggested by a pioneering experiment on a {sup 9}Be target at the CERN PS. There were reported to be two narrow ({Gamma} < 8 MeV) peaks in the continuum region. This finding was quite unexpected since the widths of {Sigma} states were believed to be large due to the strong conversion process. It is obvious that if such relatively long-lived systems were confirmed unambiguously by experiment, their masses and widths provide important constraints on the {Sigma}N effective interaction and its relation to the {Lambda}N and NN interactions. Since the {Sigma} carries isospin, the role of isospin and isospin conservation in hadronic reactions could be explored. This report stimulated a number of subsequent experiments at the BNL-AGS and KEK, along with further experiments with a specially created short kaon beam at the CERN PS. Experimental data were reported for different targets at different momenta and at different conditions. Various tagging techniques were employed to suppress backgrounds, but always at the expense of a reduction in statistical quality. Because of problems with resolution and statistics, contradictions among the different sets of data resulted more often in clouding the issues than clarifying them. Thus, up until a few years ago, there was no statistically clear confirmation of this surprising finding. In the last few years, however, a series of definitive experiments has been performed at the BNL-AGS in an effort to resolve the discrepancies and settle the controversy. Besides repeating the initial experiment on Be, a target of {sup 6}Li was run. The earlier stopped kaon data on {sup 4}He was repeated in an in-flight experiment, and the suggestion of a {Sigma} bound state, with virtually pure isospin, confirmed. We now have a better understanding of the role

  19. Dual Positive Feedback Regulation of Protein Degradation of an Extra-cytoplasmic Function σ Factor for Cell Differentiation in Streptomyces coelicolor *

    PubMed Central

    Mao, Xu-Ming; Sun, Ning; Wang, Feng; Luo, Shuai; Zhou, Zhan; Feng, Wei-Hong; Huang, Fang-Liang; Li, Yong-Quan

    2013-01-01

    Here we report that in Streptomyces coelicolor, the protein stability of an ECF σ factor SigT, which is involved in the negative regulation of cell differentiation, was completely dependent on its cognate anti-σ factor RstA. The degradation of RstA caused a ClpP/SsrA-dependent degradation of SigT during cell differentiation. This was consistent with the delayed morphological development or secondary metabolism in the ΔclpP background after rstA deletion or sigT overexpression. Meanwhile, SigT negatively regulated clpP/ssrA expression by directly binding to the clpP promoter (clpPp). The SigT-clpPp interaction could be disrupted by secondary metabolites, giving rise to the stabilized SigT protein and retarded morphological development in a non-antibiotic-producing mutant. Thus a novel regulatory mechanism was revealed that the protein degradation of the ECF σ factor was initiated by the degradation of its anti-σ factor, and was accelerated in a dual positive feedback manner, through regulation by secondary metabolites, to promote rapid and irreversible development of the secondary metabolism. This ingenious cooperation of intracellular components can ensure economical and exquisite control of the ECF σ factor protein level for the proper cell differentiation in Streptomyces. PMID:24014034

  20. Theoretical study of the AlO blue-green (B2Sigma + - X2Sigma +) band system

    NASA Technical Reports Server (NTRS)

    Partridge, H.; Langhoff, S. R.; Lengsfield, B. H., III; Liu, B.

    1983-01-01

    Two independent, extensive theoretical calculations are reported for the relative band strengths of the AlO (B2Sigma + - X2Sigma +) blue-green system and for the radiative lifetimes of the lowest few vibrational levels of the B2Sigma(+) state. The theoretical lifetimes, which include a small (less than -.5 percent) contribution from bound-bound transitions into the A2Pi state, are in excellent agreement with laser fluorescence studies. The theoretical lifetimes increase monotonically and very slowly with increasing vibrational quantum number. The relative band strengths for the blue-green system derived from the two theoretical calculations are in excellent agreement, but differ systematically from the relative band strengths of Linton and Nicholls (1969). The present results suggest that their self-absorption corrections are not large enough, resulting in relative intensities that are too large, especially for the weak bands with r centroids less than 1.5 A.

  1. Pyridoxamine is a substrate of the energy-coupling factor transporter HmpT

    PubMed Central

    Wang, Tingliang; de Jesus, Armando Jerome; Shi, Yigong; Yin, Hang

    2015-01-01

    Energy-coupling factor (ECF) transporters belong to a novel family of proteins that forms a subset within the ATP-binding cassette (ABC) transporter family. These proteins are responsible for the uptake of micronutrients in bacteria. ECF transporters are composed of four proteins: the A- and A′-components, the T-component and the S-component. One of the ECF transporters, named HmpT, was crystallized in the apo form with all four components. It is currently unknown whether HmpT serves as a transporter for hydroxymethyl pyrimidine or the different forms of vitamin B6 (pyridoxine, pyridoxal or pyridoxamine). Using a combination of molecular dynamics (MD) simulations and mass spectrometry, we have identified pyridoxamine to be the preferred substrate of HmpT. Mass spectra show that the mass of the substrate from the HmpT–substrate complex matches that of pyridoxamine. MD simulations likewise indicate that pyridoxamine interacts most strongly with most of the conserved residues of the S-component (Glu 41, His 84 and Gln 43) compared with the other vitamin B6 forms. Furthermore, the simulations have implied that loops 1 and 5 of the S-component can participate in the gating action for HmpT. PMID:27462413

  2. rpoD operon promoter used by sigma/sup H/-RNA polymerase in Bacillus subtilis

    SciTech Connect

    Carter, H.L. III; Wang, L.F.; Doi, R.H.; Moran, C.P. Jr.

    1988-04-01

    Three promoters direct transcription of the sigA (rpoD) operon in Bacillus subtilis. Promoters P1 and P2 are used during the exponential growth phase, whereas P3 is used only during the stationary phase. We examined the use of these promoters in promoter-probe plasmids and found that expression from P3 was prevented by a mutation in spoOH, which encodes the secondary RNA polymerase sigma factor sigma/sup H/. Moreover, we found that sigma/sup H/-containing RNA polymerase efficiently and accurately used the P3 promoter in vitro. Evidently, this operon, which is essential for exponential growth, is transcribed during the early phase of sporulation by this secondary form of RNA polymerase. Comparison of the nucleotide sequences of the P3 promoter and the spoVG promoter, which also is used by ..beta../sup H/-RNA polymerase, revealed sequences at the -10 and -35 regions of these promoters that may signal recognition of promoters by sigma/sup H/-RNA polymerase.

  3. Ratio of SigmaL/SigmaT for p(e,e'K+) Lambda extracted from polarization transfer

    SciTech Connect

    Daniel Carman; Brian Raue

    2005-06-01

    The ratio of longitudinal to transverse structure functions, {sigma}{sub L}/{sigma}{sub T}, has been extracted from recent beam-recoil transferred polarization data for the p({rvec e},e'K{sup +}) {rvec {Lambda}} reaction. Results have been obtained for W = 1.72, 1.84, and 1.98 GeV at an average Q{sup 2} of 0.77, 0.69, and 0.61 GeV{sup 2}, respectively. Our results indicate a ratio that is systematically slightly smaller than previously published results using a Rosenbluth separation.

  4. Establishment of a counter-selectable markerless mutagenesis system in Veillonella atypica.

    PubMed

    Zhou, Peng; Li, Xiaoli; Qi, Fengxia

    2015-05-01

    Using an alternative sigma factor ecf3 as target, we successfully established the first markerless mutagenesis system in the Veillonella genus. This system will be a valuable tool for mutagenesis of multiple genes for gene function analysis as well as for gene regulation studies in Veillonella. PMID:25771833

  5. AlgU controls expression of virulence genes in Pseudomonas syringae pv. tomato DC3000

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant pathogenic bacteria are able to integrate information about their environment and adjust gene expression to provide adaptive functions. AlgU, an ECF sigma factor encoded by Pseudomonas syringae, controls expression of genes for alginate biosynthesis and is active while the bacteria are associa...

  6. Characterization of the PvdS-regulated promoter motif in Pseudomonas syringae pv. tomato DC3000 reveals regulon members and insights regarding PvdS function in other pseudomonads

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Species of bacteria with lifestyles that require adapting to changing environmental conditions to survive are equipped with an assortment of genetic regulators to meet these challenges. The group IV or extracytoplasmic function (ECF) sigma factors regulate gene expression in response to specific en...

  7. Why is "S" a Biased Estimate of [sigma]?

    ERIC Educational Resources Information Center

    Sanqui, Jose Almer T.; Arnholt, Alan T.

    2011-01-01

    This article describes a simulation activity that can be used to help students see that the estimator "S" is a biased estimator of [sigma]. The activity can be implemented using either a statistical package such as R, Minitab, or a Web applet. In the activity, the students investigate and compare the bias of "S" when sampling from different…

  8. Strategically Focused Training in Six Sigma Way: A Case Study

    ERIC Educational Resources Information Center

    Pandey, Ashish

    2007-01-01

    Purpose: The purpose of the current study is to examine the utility of Six Sigma interventions as a performance measure and explore its applicability for making the training design and delivery operationally efficient and strategically effective. Design/methodology/approach: This is a single revelatory case study. Data were collected from multiple…

  9. SIGMA Release v1.2 - Capabilities, Enhancements and Fixes

    SciTech Connect

    Mahadevan, Vijay; Grindeanu, Iulian R.; Ray, Navamita; Jain, Rajeev; Wu, Danqing

    2015-09-30

    In this report, we present details on SIGMA toolkit along with its component structure, capabilities, and feature additions in FY15, release cycles, and continuous integration process. These software processes along with updated documentation are imperative to successfully integrate and utilize in several applications including the SHARP coupled analysis toolkit for reactor core systems funded under the NEAMS DOE-NE program.

  10. Off-Shell Structure of the String Sigma Model

    SciTech Connect

    Alan Kostelecky, V.; Perry, Malcolm J.; Potting, Robertus

    2000-05-15

    The off-shell structure of the string sigma model is investigated. In the open bosonic string, nonperturbative effects appear to depend crucially on the regularization scheme. A scheme retaining the notion of string width reproduces the structure of Witten's string field theory. (c) 2000 The American Physical Society.

  11. Shake for Sigma, Pray for Pi: Classroom Orbital Overlap Analogies

    ERIC Educational Resources Information Center

    Dicks, Andrew P.

    2011-01-01

    An introductory organic classroom demonstration is discussed where analogies are made between common societal hand contact and covalent bond formation. A handshake signifies creation of a [sigma] bond ("head-on" orbital overlap), whereas the action of praying illustrates "sideways" overlap and generation of a [pi] bond. The nature of orbital and…

  12. Making supersymmetric connected N =(0 ,2 ) sigma models

    NASA Astrophysics Data System (ADS)

    Shifman, Mikhail; Vainshtein, Arkady; Yung, Alexei

    2015-02-01

    We construct "connected" (0, 2) sigma models starting from n copies of (2, 2) CP (N -1 ) models. General aspects of models of this type (known as T +O deformations) had been previously studied in the context of heterotic string theories. Our construction presents a natural generalization of the nonminimally deformed (2, 2) model with an extra (0, 2) fermion superfield on tangent bundle T [CP (N -1 )×C1] . We had thoroughly analyzed the latter model previously and found the exact β function and a spontaneous breaking of supersymmetry. In contrast, in certain connected sigma models the spontaneous breaking of supersymmetry disappears. We study the connected sigma models in the large-N limit finding supersymmetric vacua and determining the particle spectrum. While the Witten index vanishes in all the models under consideration, in these special cases of connected models, one can use a permutation symmetry to define a modification of the Witten index which does not vanish. This eliminates the spontaneous breaking of supersymmetry. We then examine the exact β functions of our connected (0, 2) sigma models.

  13. Sigma ligand S14905 and locomotor activity in mice.

    PubMed

    Hascoet, M; Bourin, M; Payeur, R; Lombet, A; Peglion, J L

    1995-12-01

    The binding and locomotor profile of a new sigma ligand, S14905, (isobutyl-N-(1-indan-2yl-piperid-4-yl)N-methyl carbamate, furamate) was studied. The binding data revealed that S14905 has a high affinity for sigma receptors and very low affinity for both dopamine D1 and D2 receptors. We have demonstrated that this sigma ligand prevents the locomotor stimulation induced by morphine (32 and 64 mg/kg), cocaine (16 mg/kg), amphetamine (4 mg/kg) and adrafinil (32 mg/kg) at doses lower than those required to depress spontaneous locomotor activity. The antagonism observed in the present study seems to be more specific of morphine induced hyperlocomotion. The high affinity of this compound for sigma receptors makes it a good choice to study the role of this receptor in the CNS. In addition, S14905 does not directly block dopamine receptors but may modulate them in some manner, and would thus warrant further study as a potential atypical antipsychotic agent, and an antagonist for the hyperactivity induced by opiate drug. PMID:8998401

  14. Using Six-Sigma To Change and Measure Improvement.

    ERIC Educational Resources Information Center

    Feld, Karl G.; Stone, William K.

    2002-01-01

    Explains why Honeywell's Market Research Department replaced its traditional data collection and paper-based tabulation with blended modes, including electronic interviewing and real-time reporting. Describes how the Six-Sigma quality control process demonstrated that a hybrid approach with blended modes and Web-based reporting tools could deliver…

  15. The Exposure Rate Conversion Factor for Nuclear Fallout

    SciTech Connect

    Spriggs, G D

    2009-02-11

    Nuclear fallout is comprised of approximately 2000 radionuclides. About 1000 of these radionuclides are either primary fission products or activated fission products that are created during the burn process. The exposure rate one meter above the surface produced by this complex mixture of radionuclides varies rapidly with time since many of the radionuclides are short-lived and decay numerous times before reaching a stable isotope. As a result, the mixture of radionuclides changes rapidly with time. Using a new code developed at the Lawrence Livermore National Laboratory, the mixture of radionuclides at any given point in time can be calculated. The code also calculates the exposure rate conversion factor (ECF) for all 3864 individual isotopes contained in its database based on the total gamma energy released per decay. Based on the combination of isotope mixture and individual ECFs, the time-dependent variation of the composite exposure rate conversion factor for nuclear fallout can be easily calculated. As example of this new capability, a simple test case corresponding to a 10 kt, uranium-plutonium fuel has been calculated. The results for the time-dependent, composite ECF for this test case are shown in Figure 1. For comparison, we also calculated the composite exposure rate conversion factor using the conversion factors found in Federal Guidance Report No.12 (FGR-12) published by ORNL, which contains the conversion factors for approximately 1000 isotopes. As can be noted from Figure 1, the two functions agree reasonably well at times greater than about 30 minutes. However, they do not agree at early times since FGR-12 does not include all of the short-lived isotopes that are produced in nuclear fallout. It should also be noted that the composite ECF at one hour is 19.7 R/hr per Ci/m{sup 2}. This corresponds to 3148 R/hr per 1 kt per square mile, which agrees reasonably well with the value of 3000 R/hr per 1 kt per square mile as quoted by Glasstone. We have

  16. Photochemistry of dianthrylsilanes: a study of sigma,pi-interaction.

    PubMed

    Yang, Ding-Djung H; Yang, Nien-Chu C; Steele, Ian M; Li, Hui; Ma, Ying-Zhong; Fleming, Graham R

    2003-04-30

    In this article, we demonstrated by the application of time-resolved spectroscopy, X-ray structural analysis and other spectroscopic techniques that 9-Anthrylsilanes exhibits sigma,pi-interaction between 9-anthryl group and the Si-Si linkage in anthryl-disilanes, ASi(2), ASi(2)A, and ASi(3)A which does not occur in the analogous alkyl derivatives as well as the pyrenylsilane derivatives, in spite of the fact that the 0,0-band of PSi(2) is about 12.8 KJ more energetic than that of ASi(2) (Figure 1). More interestingly, the X-ray structural studies reveal that ASi(3)A exists in a butterfly-like structure in agreement with other spectroscopic analyses that the two anthryl groups do not interact in their excited states, while those in ASi(2)A do. This is in contrast to the analogous pyrenylsilanes; the trisilanes exhibits a stronger excimer interaction than that of disilane.(10b) Our results show that the sigma,pi-interactions in ASi(3)A has imparted rigidity to the tri-silyl linkage. Potential applications of anthrylsilanes in material sciences will be explored.(5) This work provides evidence that sigma,pi-interaction between the 9-anthryl group and disilyl linkage does play an important role in the properties of disilanes. We attribute this enhanced sigma,pi-interaction to the nature of the lowest excited state (S(1) state) of anthracenes, the L(a) transition, which has a much higher oscillator strength than the S(1)L(b)-transition of pyrenes (Figure 1). We define the interaction in anthracene as a sigma,pi(S(1,)L(a)) interaction. This interaction lends a substantial barrier to the Si-Si bond with the excited anthryl nucleus in anthrylsilanes. The scope and potential applications of this phenomenon are discussed. PMID:12708861

  17. Analysis of Single-Earthquake Sigma Using Taiwan Dataset

    NASA Astrophysics Data System (ADS)

    SUNG, C.; Lee, C.

    2011-12-01

    The standard deviation of the logarithmic residuals in ground-motion prediction may directly influence the result of probabilistic seismic hazard analysis, especially in lower probability. "What method can reduce the sigma more?" is usually a hot issue in recent years. Now, we not only pay attention to this point, but also focus on "How the minimum variance of ground motion residuals from median attenuation can be got in nature". In this study, we used 23 Taiwan earthquakes, which have been recorded by more than 500 stations, to find out the facts. The single earthquake ground-motion attenuation form includes only propagation parameter and site parameter, because the source term is fixed. After regression using maximum likelihood method, we calculate a ground-motion residual for each station and plot the distribution. Even if the stations are very close to each other (the wave paths are very similar) or the stations are the same (the wave paths are the same), their residual still have difference. We also calculate a mean residual and a standard deviation for each 5km × 5km cell and evaluate the trend at different paths. The standard deviations of ln(PGA) for cells and earthquakes range from 0.2 to 0.6. We further analyze the single path sigma by using variogram method. We measure semi-variances at different distance bins (lags) and plot a semi-variogram. Nugget effect is commonly found in each single earthquake. This means even the distance between two stations is equal to zero; there still is significant difference in ground-motion residual. The single path sigma of ln(PGA) for earthquakes range from 0.32 to 0.56. The reduction of single path sigma (σsp) from the total sigma for earthquakes (σT) range from 20% to 40%.

  18. First Measurement of sigma(gg -> ttbar)/sigma(ppbar -> ttbar)

    SciTech Connect

    Pashapour Alamdari, Shabnaz; /Toronto U.

    2008-06-01

    The work presented here is the first measurement of the fraction of top quark pair production through gluon-gluon fusion. We use an integrated luminosity of 0.96 {+-} 0.06 fb{sup -1} of p{bar p} collisions at {radical}s of 1.96 TeV collected by the CDF II detector. We select t{bar t} candidates by identifying a high-p{sub T} lepton candidate, a large missing E{sub T} as evidence for a neutrino candidate and at least four high E{sub T} jets, one of which has to be identified as originating from a b quark. The challenge is to discriminate between the two production processes with the identical final state, gg {yields} t{bar t} and q{bar q} {yields} t{bar t}. We take advantage of the fact that compared to a quark, a gluon is more likely to radiate a low momentum gluon and therefore, one expects a larger number of charged particles with low p{sub T} in a process involving more gluons. Given the large uncertainties associated with the modeling of the low p{sub T} charged particle multiplicity, a data-driven technique was employed. Using calibration data samples, we show there exists a clear correlation between the observed average number of low p{sub T} charged particles and the average number of gluons involved in the production process predicted by Monte Carlo calculations. Given the correlation, one can identify low p{sub T} charged particle multiplicity distributions associated with specific average number of gluons. The W + 0 jet sample and dijets sample with leading jet E{sub T} in the range of 80-100 GeV are used to find no-gluon and gluon-rich low p{sub T} charged particle multiplicity distributions, respectively. Using these no-gluon and gluon-rich distributions in a likelihood fit, we find the fraction of gluon-rich events in t{bar t} candidates. This fraction has contributions from the signal and background events. Taking into account these contributions and the gg {yields} t{bar t} and q{bar q} {yields} t{bar t} production channel acceptances, we find {sigma

  19. Lean and Six Sigma in acute care: a systematic review of reviews.

    PubMed

    Deblois, Simon; Lepanto, Luigi

    2016-03-14

    Purpose - The purpose of this paper is to present a systematic review of literature reviews, summarizing how Lean and Six Sigma management techniques have been implemented in acute care settings to date, and assessing their impact. To aid decision makers who wish to use these techniques by identifying the sectors of activity most often targeted, the main results of the interventions, as well as barriers and facilitators involved. To identify areas of future research. Design/methodology/approach - A literature search was conducted, using eight databases. The methodological quality of the selected reviews was appraised with AMSTAR. A narrative synthesis was performed according to the guidelines proposed by Popay et al. (2006). Data were reported according to PRISMA. Findings - The literature search identified 149 publications published from 1999 to January 2015. Seven literature reviews were included into the systematic review, upon appraisal. The overall quality of the evidence was poor to fair. The clinical settings most described were specialized health care services, including operating suites, intensive care units and emergency departments. The outcomes most often appraised related to processes and quality. The evidence suggests that Lean and Six Sigma are better adapted to settings where processes involve a linear sequence of events. Research limitations/implications - There is a need for more studies of high methodological quality to better understand the effects of these approaches as well as the factors of success and barriers to their implementation. Field studies comparing the effects of Lean and Six Sigma to those of other process redesign or quality improvement efforts would bring a significant contribution to the body of knowledge. Practical implications - Lean and Six Sigma can be considered valuable process optimization approaches in acute health care settings. The success of their implementation requires significant participation of clinical

  20. Six Sigma: not for the faint of heart.

    PubMed

    Benedetto, Anthony R

    2003-01-01

    Six Sigma is an excellent quality and performance improvement tool. Like any tool, the results of using it are highly dependent on whether you use it with competence and on the right problem. This article will help you decide if your problem is well-suited for a Six Sigma approach and will suggest the optimum approach for planning and implementing Six Sigma methodology. Performance improvement methods can be grouped into two broad categories, based on the problem to be addressed. When the problem is relatively minor and localized, "evolutionary" methods may be suitable (e.g., quality circles, problem-solving staff meetings, continuous quality improvement [CQI], total quality management [TQM]). These tools work best when modest incremental improvements are sought, when major process redesign is not thought to be necessary, and when the avoidance of workplace disruption is desired. Reengineering and Six Sigma are the best-known examples of the "revolutionary" performance improvement methods. These methods should be used when major (drastic, do or die, etc.) improvements are needed. Problems that cross departmental boundaries need these methods. When a process is so dysfunctional that you feel like you need to tear up the standard operating procedure (SOP) and start all over again, you need a revolutionary method. A Six Sigma project requires a major expenditure of money and employee time, and a willingness to make some hard decisions about jobs, employee retention and relationships among stakeholders. An institution's culture should be considered as part of the decision about using Six Sigma. If the institution has a history of making data-driven decisions, or at least has displayed openness to operating in that manner, Six Sigma has a good chance of success. A radiology-driven Six Sigma project should not be undertaken until a comprehensive written description of the scope of the project is approved by the radiology department leadership team and by the appropriate

  1. A Framework for Six Sigma Project Selection in Higher Educational Institutions, Using a Weighted Scorecard Approach

    ERIC Educational Resources Information Center

    Holmes, Monica C.; Jenicke, Lawrence O.; Hempel, Jessica L.

    2015-01-01

    Purpose: This paper discusses the importance of the Six Sigma selection process, describes a Six Sigma project in a higher educational institution and presents a weighted scorecard approach for project selection. Design/Methodology/Approach: A case study of the Six Sigma approach being used to improve student support at a university computer help…

  2. Inhibition of tumor cell growth by Sigma1 ligand mediated translational repression

    SciTech Connect

    Kim, Felix J.; Schrock, Joel M.; Spino, Christina M.; Marino, Jacqueline C.; Pasternak, Gavril W.

    2012-09-21

    Highlights: Black-Right-Pointing-Pointer Sigma1 ligand treatment mediates decrease in tumor cell mass. Black-Right-Pointing-Pointer Identification of a Sigma1 ligand with reversible translational repressor actions. Black-Right-Pointing-Pointer Demonstration of a role for Sigma1 in cellular protein synthesis. -- Abstract: Treatment with sigma1 receptor (Sigma1) ligands can inhibit cell proliferation in vitro and tumor growth in vivo. However, the cellular pathways engaged in response to Sigma1 ligand treatment that contribute to these outcomes remain largely undefined. Here, we show that treatment with putative antagonists of Sigma1 decreases cell mass. This effect corresponds with repressed cap-dependent translation initiation in multiple breast and prostate cancer cell lines. Sigma1 antagonist treatment suppresses phosphorylation of translational regulator proteins p70S6K, S6, and 4E-BP1. RNAi-mediated knockdown of Sigma1 also results in translational repression, consistent with the effects of antagonist treatment. Sigma1 antagonist mediated translational repression and decreased cell size are both reversible. Together, these data reveal a role for Sigma1 in tumor cell protein synthesis, and demonstrate that small molecule Sigma1 ligands can be used as modulators of protein translation.

  3. Target space pseudoduality in supersymmetric sigma models on symmetric spaces

    NASA Astrophysics Data System (ADS)

    Sarisaman, Mustafa

    We discuss the target space pseudoduality in supersymmetric sigma models on symmetric spaces. We first consider the case where sigma models based on real compact connected Lie groups of the same dimensionality and give examples using three dimensional models on target spaces. We show explicit construction of nonlocal conserved currents on the pseudodual manifold. We then switch the Lie group valued pseudoduality equations to Lie algebra valued ones, which leads to an infinite number of pseudoduality equations. We obtain an infinite number of conserved currents on the tangent bundle of the pseudo-dual manifold. Since pseudoduality imposes the condition that sigma models pseudodual to each other are based on symmetric spaces with opposite curvatures (i.e. dual symmetric spaces), we investigate pseudoduality transformation on the symmetric space sigma models in the third chapter. We see that there can be mixing of decomposed spaces with each other, which leads to mixings of the following expressions. We obtain the pseudodual conserved currents which are viewed as the orthonormal frame on the pullback bundle of the tangent space of G˜ which is the Lie group on which the pseudodual model based. Hence we obtain the mixing forms of curvature relations and one loop renormalization group beta function by means of these currents. In chapter four, we generalize the classical construction of pseudoduality transformation to supersymmetric case. We perform this both by component expansion method on manifold M and by orthonormal coframe method on manifold SO( M). The component method produces the result that pseudoduality transformation is not invertible at all points and occurs from all points on one manifold to only one point where riemann normal coordinates valid on the second manifold. Torsion of the sigma model on M must vanish while it is nonvanishing on M˜, and curvatures of the manifolds must be constant and the same because of anticommuting grassmann numbers. We obtain

  4. Transcriptional organization and in vivo role of the Escherichia coli rsd gene, encoding the regulator of RNA polymerase sigma D.

    PubMed

    Jishage, M; Ishihama, A

    1999-06-01

    The regulator of sigma D (Rsd) was identified as an RNA polymerase sigma70-associated protein in stationary-phase Escherichia coli with the inhibitory activity of sigma70-dependent transcription in vitro (M. Jishage and A. Ishihama, Proc. Natl. Acad. Sci. USA 95:4953-4958, 1998). Primer extension analysis of rsd mRNA indicated the presence of two promoters, sigmaS-dependent P1 and sigma70-dependent P2 with the gearbox sequence. To get insight into the in vivo role of Rsd, the expression of a reporter gene fused to either the sigma70- or sigmaS-dependent promoter was analyzed in the absence of Rsd or the presence of overexpressed Rsd. In the rsd null mutant, the sigma70- and sigmaS-dependent gene expression was increased or decreased, respectively. On the other hand, the sigma70- or sigmaS-dependent transcription was reduced or enhanced, respectively, after overexpression of Rsd. The repression of the sigmaS-dependent transcription in the rsd mutant is overcome by increased production of the sigmaS subunit. Together these observations support the prediction that Rsd is involved in replacement of the RNA polymerase sigma subunit from sigma70 to sigmaS during the transition from exponential growth to the stationary phase. PMID:10368152

  5. Suppression of the {Lambda}-{Sigma} coupling in nuclear matter

    SciTech Connect

    Bodmer, A.R.; Usmani, Q.N.

    1995-08-01

    We initiated a study of the modification of the coupling of the {Lambda}N to the {Sigma}N channel in nuclear matter with the Fermi hypernetted-chain variational approach. This modification of the {Lambda}N-{Sigma}N coupling is a central problem in hypernuclear physics and is related closely to the strongly repulsive three-body forces which are needed to account for hypernuclear binding energies. All earlier calculations have only considered this problem in the so-called G-matrix approximation which neglects important higher-order effects. An important result of this work will be a better understanding of the density dependence of {Lambda} binding in nuclear matter, which can then be tested in the calculation of the {Lambda} single-particle energies.

  6. Rethinking behavioral health processes by using design for six sigma.

    PubMed

    Lucas, Anthony G; Primus, Kelly; Kovach, Jamison V; Fredendall, Lawrence D

    2015-02-01

    Clinical evidence-based practices are strongly encouraged and commonly utilized in the behavioral health community. However, evidence-based practices that are related to quality improvement processes, such as Design for Six Sigma, are often not used in behavioral health care. This column describes the unique partnership formed between a behavioral health care provider in the greater Pittsburgh area, a nonprofit oversight and monitoring agency for behavioral health services, and academic researchers. The authors detail how the partnership used the multistep process outlined in Design for Six Sigma to completely redesign the provider's intake process. Implementation of the redesigned process increased access to care, decreased bad debt and uncollected funds, and improved cash flow--while consumer satisfaction remained high. PMID:25642607

  7. Observation of the sigma_b baryons at CDF

    SciTech Connect

    Pursley, Jennifer M.; /Johns Hopkins U.

    2007-03-01

    We present a measurement of four new bottom baryons in proton-antiproton collisions with a center of mass energy of 1.96 TeV. Using 1.1 fb{sup -1} of data collected by the CDF II detector, we observe four {Lambda}{sup 0}{sub b}{pi}{+-} resonances in the fully reconstructed decay mode {Lambda}{sup 0}{sub b} {yields} {Lambda}{sup +}{sub c}{pi}{sup -}, where {Lambda}{sup +}{sub c} {yields} pK{sup -}{pi}{sup +}. The probability for the background to produce a similar or larger signal is less than 8.3 x 10{sup -8}, corresponding to a significance of greater than 5.2 {sigma}. We interpret these baryons as the {Sigma}{sub b}{sup (*){+-}} baryons.

  8. Digital pixel sensor array with logarithmic delta-sigma architecture.

    PubMed

    Mahmoodi, Alireza; Li, Jing; Joseph, Dileepan

    2013-01-01

    Like the human eye, logarithmic image sensors achieve wide dynamic range easily at video rates, but, unlike the human eye, they suffer from low peak signal-to-noise-and-distortion ratios (PSNDRs). To improve the PSNDR, we propose integrating a delta-sigma analog-to-digital converter (ADC) in each pixel. An image sensor employing this architecture is designed, built and tested in 0.18 micron complementary metal-oxide-semiconductor (CMOS) technology. It achieves a PSNDR better than state-of-the-art logarithmic sensors and comparable to the human eye. As the approach concerns an array of many ADCs, we use a small-area low-power delta-sigma design. For scalability, each pixel has its own decimator. The prototype is compared to a variety of other image sensors, linear and nonlinear, from industry and academia. PMID:23959239

  9. Pseudo-random number generator for the Sigma 5 computer

    NASA Technical Reports Server (NTRS)

    Carroll, S. N.

    1983-01-01

    A technique is presented for developing a pseudo-random number generator based on the linear congruential form. The two numbers used for the generator are a prime number and a corresponding primitive root, where the prime is the largest prime number that can be accurately represented on a particular computer. The primitive root is selected by applying Marsaglia's lattice test. The technique presented was applied to write a random number program for the Sigma 5 computer. The new program, named S:RANDOM1, is judged to be superior to the older program named S:RANDOM. For applications requiring several independent random number generators, a table is included showing several acceptable primitive roots. The technique and programs described can be applied to any computer having word length different from that of the Sigma 5.

  10. Is health care ready for Six Sigma quality?

    PubMed

    Chassin, M R

    1998-01-01

    Serious, widespread problems exist in the quality of U.S. health care: too many patients are exposed to the risks of unnecessary services; opportunities to use effective care are missed; and preventable errors lead to injuries. Advanced practitioners of industrial quality management, like Motorola and General Electric, have committed themselves to reducing the frequency of defects in their business processes to fewer than 3.4 per million, a strategy known as Six Sigma Quality. In health care, quality problems frequently occur at rates of 20 to 50 percent, or 200,000 to 500,000 per million. In order to approach Six Sigma levels of quality, the health care sector must address the underlying causes of error and make important changes: adopting new educational models; devising strategies to increase consumer awareness; and encouraging public and private investment in quality improvement. PMID:9879303

  11. Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury.

    PubMed

    Dong, Hui; Ma, Yunfu; Ren, Zengxi; Xu, Bin; Zhang, Yunhe; Chen, Jing; Yang, Bo

    2016-07-01

    Traumatic brain injury (TBI) remains a significant clinical problem and contributes to one-third of all injury-related deaths. Activated microglia-mediated inflammatory response is a distinct characteristic underlying pathophysiology of TBI. Here, we evaluated the effect and possible mechanisms of the selective Sigma-1 receptor agonist 2-(4-morpholinethyl)-1-phenylcyclohexanecarboxylate (PRE-084) in mice TBI model. A single intraperitoneal injection 10 μg/g PRE-084, given 15 min after TBI significantly reduced lesion volume, lessened brain edema, attenuated modified neurological severity score, increased the latency time in wire hang test, and accelerated body weight recovery. Moreover, immunohistochemical analysis with Iba1 staining showed that PRE-084 lessened microglia activation. Meanwhile, PRE-084 reduced nitrosative and oxidative stress to proteins. Thus, Sigma-1 receptors play a major role in inflammatory response after TBI and may serve as useful target for TBI treatment in the future. PMID:26228028

  12. The moduli space of superconformal instantons in sigma models

    SciTech Connect

    Monastyrsky, M.I. ); Natanzon, S.M. )

    1991-06-21

    In this paper, an approach to instantons in supersymmetrical 2-dimensional sigma models is discussed. In this approach superinstantons are characterized as the superconformal maps of a physical space into the isotopic (target) space. The authors consider a special case of the supersphere with punctures. New topological invariants as the number of the so-called fermionic points appear in this case. The authors also analyze the structure of the moduli space of superinstantons within this framework.

  13. A symmetric approach to the massive nonlinear sigma model

    DOE PAGESBeta

    Ferrari, Ruggero

    2011-09-28

    In the present study we extend to the massive case the procedure of divergences subtraction, previously introduced for the massless nonlinear sigma model (D = 4). Perturbative expansion in the number of loops is successfully constructed. The resulting theory depends on the Spontaneous Symmetry Breaking parameter v, on the mass m and on the radiative correction parameter Λ. Fermions are not considered in the present work. SU(2) Ⓧ SU(2) is the group used.

  14. Effects of conformational distributions on sigma profiles in COSMO theories.

    PubMed

    Wang, Shu; Stubbs, John M; Siepmann, J Ilja; Sandler, Stanley I

    2005-12-15

    The charge density or sigma profile of a solute molecule is an essential component in COSMO (conductor-like screen model) based solvation theories, and its generation depends on the molecular conformation used. The usual procedure is to determine the conformation of an isolated molecule, and assume that this is unchanged when the molecule is placed in solution. In this paper, the conformations of 1-hexanol and 2-methoxy-ethanol in both the liquid and vapor phases obtained from Gibbs ensemble simulation and from an isolated-molecule quantum DFT optimization are used to determine the effect of realistic conformation differences on COSMO-based properties predictions. In particular, the vapor pressure at the normal boiling temperature and the binary mixture VLE (vapor-liquid equilibrium) predictions obtained using different conformations are investigated. The results show that the sigma profile for 1-hexanol varies only slightly using the different conformations, while the sigma profile of 2-methoxy-ethanol shows a significant difference between the liquid and vapor phases. Consequently, the vapor pressure predictions for 1-hexanol are similar regardless of the manner in which the conformation population was obtained, while there is a larger difference for 2-methoxy-ethanol depending on whether the liquid or vapor conformations from simulation or the DFT-optimized structure is used. These differences in predictions are seen to be largely due to differences in the ideal solvation energy term. In mixture VLE calculations involving 1-hexanol, we again see that there is little difference in the phase equilibrium predictions among the different conformations, while for the mixture with 2-methoxy-ethanol, the differences in the sigma profiles lead to a more noticeable, though not significant, difference in the phase equilibrium predictions. PMID:16331913

  15. Linear Sigma Model Toolshed for D-brane Physics

    SciTech Connect

    Hellerman, Simeon

    2001-08-23

    Building on earlier work, we construct linear sigma models for strings on curved spaces in the presence of branes. Our models include an extremely general class of brane-worldvolume gauge field configurations. We explain in an accessible manner the mathematical ideas which suggest appropriate worldsheet interactions for generating a given open string background. This construction provides an explanation for the appearance of the derived category in D-brane physic complementary to that of recent work of Douglas.

  16. Highly excited {Sigma}{sup -} states of molecular hydrogen

    SciTech Connect

    Argoubi, F.; Bezzaouia, S.; Oueslati, H.; Telmini, M.; Jungen, Ch.

    2011-05-15

    We report calculations of H{sub 2} {Sigma}{sup -} states using a variational R-matrix approach combined with multichannel quantum defect theory. Several Rydberg series converging to the 2p{pi} state of the H{sub 2}{sup +} ion core are established and their mutual channel interactions characterized. The influence of the external electron on the chemical bond is found to be particularly strong in these electronically and chemically weakly bound states.

  17. Geometry of surfaces associated to Grassmannian sigma models

    NASA Astrophysics Data System (ADS)

    Delisle, L.; Hussin, V.; Zakrzewski, W. J.

    2015-04-01

    We investigate the geometric characteristics of constant Gaussian curvature surfaces obtained from solutions of the G(m, n) sigma model. Most of these solutions are related to the Veronese sequence. We show that we can distinguish surfaces with the same Gaussian curvature using additional quantities like the topological charge and the mean curvature. The cases of G(1,n) = CPn-1 and G(2,n) are used to illustrate these characteristics.

  18. Integration of massive states as contractions of nonlinear {sigma} models

    SciTech Connect

    Andrianopoli, L.; Ferrara, S.; Lledo, M.A.; Macia, O.

    2005-07-01

    We consider the contraction of some nonlinear {sigma} models which appear in effective supergravity theories. In particular we consider the contractions of maximally symmetric spaces corresponding to N=1 and N=2 theories, as they appear in certain low energy effective supergravity actions with mass deformations. The contraction procedure is shown to describe the integrating out of massive modes in the presence of interactions, as it happens in many supergravity models after spontaneous supersymmetry breaking.

  19. Isolation Amplifier Based On Sigma-Delta Modulation

    NASA Technical Reports Server (NTRS)

    Harres, Daniel N.

    1994-01-01

    Improved isolation amplifier transmits dc or low-frequency analog signal by use of digital pulses. Relatively imprecise digital pulses convey analog signal with relatively high precision. Amplifier implements sigma-delta modulation scheme. Circuit used wherever conventional amplifier needed. Includes medical instrumentation, switching-type power supplies, and other applications in which input voltages must be measured in presence of large common-mode voltages.

  20. Topological Twisted Sigma Model with H-flux Revisited

    SciTech Connect

    Chuang, Wu-yen

    2006-08-18

    In this paper we revisit the topological twisted sigma model with H-flux. We explicitly expand and then twist the worldsheet Lagrangian for bi-Hermitian geometry. we show that the resulting action consists of a BRST exact term and pullback terms, which only depend on one of the two generalized complex structures and the B-field. We then discuss the topological feature of the model.

  1. A six-sigma approach to stability testing.

    PubMed

    De Vore, Karl

    2008-06-01

    The following defines stability testing in the diagnostic and pharmaceutical industries as a process which, depending on the manufacturer's current approach, may contain many opportunities for improvement. Statistical thinking and six sigma concepts will enhance stability testing process capability and lead to higher confidence in the data. Tools for set up and the rationale behind them are provided to assist in establishing appropriate criteria and volume of testing. PMID:18262382

  2. The innovative use of Six Sigma in home care.

    PubMed

    Elberfeld, Adrienne; Bennis, Sandra; Ritzius, Jeannie; Yhlen, David

    2007-01-01

    The Prospective Payment System had significant impact on home healthcare agencies throughout the nation. Virtua Home Care, located in Southern New Jersey, realized the need for process improvement in order to remain viable. Six Sigma was introduced to the agency and the Define, Measure, Analyze, Improve, and Control processes were initiated to achieve sustainable results, and within 9 months, Virtua Home Care improved regulatory compliance, experienced a deficiency-free survey, and recognized a 1.2 million dollars financial gain. PMID:17218866

  3. Note on a sigma model connection with instanton dynamics

    SciTech Connect

    Fariborz, Amir H.

    2008-05-01

    It is well known that the instanton approach to QCD generates an effective term which looks like a three-flavor determinant of quark bilinears. This has the right behavior to explain the unusual mass and mixing of the {eta}(958) meson, as is often simply illustrated with the aid of a linear SU(3) sigma model. It is less well known that the instanton analysis generates another term which has the same transformation property but does not have a simple interpretation in terms of this usual linear sigma model. Here we point out that this term has an interpretation in a generalized linear sigma model containing two chiral nonets. The second chiral nonet is taken to correspond to mesons having two quarks and two antiquarks in their makeup. The generalized model seems to be useful for learning about the spectrum of low-lying scalar mesons which have been emerging in the last few years. The physics of the new term is shown to be related to the properties of an excited {eta}{sup '} state present in the generalized model and for which there are some experimental candidates.

  4. Sigma models for genuinely non-geometric backgrounds

    NASA Astrophysics Data System (ADS)

    Chatzistavrakidis, Athanasios; Jonke, Larisa; Lechtenfeld, Olaf

    2015-11-01

    The existence of genuinely non-geometric backgrounds, i.e. ones without geometric dual, is an important question in string theory. In this paper we examine this question from a sigma model perspective. First we construct a particular class of Courant algebroids as protobialgebroids with all types of geometric and non-geometric fluxes. For such structures we apply the mathematical result that any Courant algebroid gives rise to a 3D topological sigma model of the AKSZ type and we discuss the corresponding 2D field theories. It is found that these models are always geometric, even when both 2-form and 2-vector fields are neither vanishing nor inverse of one another. Taking a further step, we suggest an extended class of 3D sigma models, whose world volume is embedded in phase space, which allow for genuinely non-geometric backgrounds. Adopting the doubled formalism such models can be related to double field theory, albeit from a world sheet perspective.

  5. Small-area decimators for delta-sigma video sensors

    NASA Astrophysics Data System (ADS)

    Azabache Villar, Erika; Skorka, Orit; Joseph, Dileepan

    2014-04-01

    A delta-sigma, or sigma-delta, analog-to-digital converter (ADC) comprises both a modulator, which implements oversampling and noise shaping, and a decimator, which implements low-pass filtering and downsampling. Whereas these ADCs are ubiquitous in audio applications, their usage in video applications is emerging. Because of oversampling, it is preferable to integrate delta-sigma ADCs at the pixel level of megapixel video sensors. Moreover, with pixel-level applications, area usage per ADC is much more important than with chip-level applications, where there is only one or a few ADCs per chip. Recently, a small-area decimator was presented that is suitable for pixel-level applications. However, though the pixel-level design is small enough for invisible-band video sensors, it is too large for visible-band ones. As shown here, nanoscale CMOS processes offer a solution to this problem. Given constant specifications, small-area decimators are designed, simulated, and laid out, full custom, for 180, 130, and 65nm standard CMOS processes. Area usage of the whole decimator is analyzed to establish a roadmap for the design and demonstrate that it could be competitive compared to other digital pixel sensors, based on Nyquist-rate ADCs, that are being commercialized.

  6. Application of Six Sigma Robust Optimization in Sheet Metal Forming

    SciTech Connect

    Li, Y.Q.; Cui, Z.S.; Ruan, X.Y.; Zhang, D.J.

    2005-08-05

    Numerical simulation technology and optimization method have been applied in sheet metal forming process to improve design quality and shorten design cycle. While the existence of fluctuation in design variables or operation condition has great influence on the quality. In addition to that, iterative solution in numerical simulation and optimization usually take huge computational time or endure expensive experiment cost In order to eliminate effect of perturbations in design and improve design efficiency, a CAE-based six sigma robust design method is developed in this paper. In the six sigma procedure for sheet metal forming, statistical technology and dual response surface approximate model as well as algorithm of 'Design for Six Sigma (DFSS)' are integrated together to perform reliability optimization and robust improvement. A deep drawing process of a rectangular cup is taken as an example to illustrate the method. The optimization solutions show that the proposed optimization procedure not only improves significantly the reliability and robustness of the forming quality, but also increases optimization efficiency with approximate model.

  7. Sigma and opioid receptors in human brain tumors

    SciTech Connect

    Thomas, G.E.; Szuecs, M.; Mamone, J.Y.; Bem, W.T.; Rush, M.D.; Johnson, F.E.; Coscia, C.J. )

    1990-01-01

    Human brain tumors and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using ({sup 3}H) 1, 3-di-o-tolylguanidine (DTG), whereas opioid receptor subtypes were measured with tritiated forms of the following: {mu}, (D-ala{sup 2}, mePhe{sup 4}, gly-ol{sup 5}) enkephalin (DAMGE); {kappa}, ethylketocyclazocine (EKC) or U69,593; {delta}, (D-pen{sup 2}, D-pen{sup 5}) enkephalin (DPDPE) or (D-ala{sup 2}, D-leu{sup 5}) enkephalin (DADLE) with {mu} suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. {kappa} opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed.

  8. Tree-level amplitudes in the nonlinear sigma model

    NASA Astrophysics Data System (ADS)

    Kampf, Karol; Novotný, Jirí; Trnka, Jaroslav

    2013-05-01

    We study in detail the general structure and further properties of the tree-level amplitudes in the SU( N) nonlinear sigma model. We construct the flavor-ordered Feynman rules for various parameterizations of the SU( N) fields U ( x), write down the Berends-Giele relations for the semi-on-shell currents and discuss their efficiency for the amplitude calculation in comparison with those of renormalizable theories. We also present an explicit form of the partial amplitudes up to ten external particles. It is well known that the standard BCFW recursive relations cannot be used for reconstruction of the the on-shell amplitudes of effective theories like the SU( N) nonlinear sigma model because of the inappropriate behavior of the deformed on-shell amplitudes at infinity. We discuss possible generalization of the BCFW approach introducing "BCFW formula with subtractions" and with help of Berends-Giele relations we prove particular scaling properties of the semi-on-shell amplitudes of the SU( N) nonlinear sigma model under specific shifts of the external momenta. These results allow us to define alternative deformation of the semi-on-shell amplitudes and derive BCFW-like recursion relations. These provide a systematic and effective tool for calculation of Goldstone bosons scattering amplitudes and it also shows the possible applicability of on-shell methods to effective field theories. We also use these BCFW-like relations for the investigation of the Adler zeroes and double soft limit of the semi-on-shell amplitudes.

  9. Non-commutativity from the double sigma model

    NASA Astrophysics Data System (ADS)

    Polyakov, Dimitri; Wang, Peng; Wu, Houwen; Yang, Haitang

    2015-03-01

    We show how non-commutativity arises from commutativity in the double sigma model. We demonstrate that this model is intrinsically non-commutative by calculating the propagators. In the simplest phase configuration, there are two dual copies of commutative theories. In general rotated frames, one gets a non-commutative theory and a commutative partner. Thus a non-vanishing B also leads to a commutative theory. Our results imply that O( D, D) symmetry unifies not only the big and small torus physics, but also the commutative and non-commutative theories. The physical interpretations of the metric and other parameters in the double sigma model are completely dictated by the boundary conditions. The open-closed relation is also an O( D, D) rotation and naturally leads to the Seiberg-Witten map. Moreover, after applying a second dual rotation, we identify the description parameter in the Seiberg-Witten map as an O( D, D) group parameter and all theories are non-commutative under this composite rotation. As a bonus, the propagators of general frames in double sigma model for open string are also presented.

  10. The massive O(N) non-linear sigma model at high orders

    NASA Astrophysics Data System (ADS)

    Bijnens, Johan; Carloni, Lisa

    2011-02-01

    We extend our earlier work on the massive O(N) non-linear sigma model to other observables. We derive expressions at leading order in the large N expansion at all orders in the loop expansion for the decay constant, vacuum expectation value, meson-meson scattering and the scalar and vector form factors. This is done using cactus diagram resummation using a generalized gap equation and other recursion relations. For general N we derive the expressions for the n-th-loop-order leading logarithms (M/Flog (/M))n, up to five loops for the decay constant and vacuum expectation value (VEV) and up to four loops for meson-meson scattering, the scalar and vector form factors. We also quote our earlier result for the mass. The large N results do not give a good approximation for the case N=3. We use our results to study the convergence of the perturbative series and compare with elastic unitarity.

  11. Structural analysis of sigma E interactions with core RNA polymerase and its cognate P-hsp20 promoter of Mycobacterium tuberculosis.

    PubMed

    Gupta, Aayatti Mallick; Pal, Purab; Mandal, Sukhendu

    2016-04-01

    Alternate sigma factor plays an important role for the survival of Mycobacterium tuberculosis in adverse environmental condition. Stress-induced sigma factors are major cause for expression of genes involved in pathogenesis, dormancy and various unusual environmental conditions. In the present work, an attempt has been made to characterize one of such M. tuberculosis (Mtb) sigma factor, SigE. The structures of Mtb-SigE and Mtb-β have been predicted using comparative modelling techniques and validated. Effort has also been implied to understand the nature of interaction of SigE with the core RNA polymerase subunits which have well identified the amino acid residues in the binding interface and prompted the fact that Mtb-β' and Mtb-β interact with domain 2 and domain 4 of Mtb-SigE, respectively. Furthermore, intermolecular docking study predicted the interface between the Mtb-SigE and its putative promoter P-hsp20. The report confers the probable amino acid residues and the nitrogenous bases involved in the recognition of P-hsp20 by the sigma factor to initiate the transcription process. PMID:26006066

  12. Operating and environmental characteristics of Sigma Tau hydrogen masers used in the Very Long Baseline Array (VLBA)

    NASA Technical Reports Server (NTRS)

    Tucker, T. K.

    1989-01-01

    Presented here are the results obtained from performance evaluation of a pair of Sigma Tau Standards Corporation Model VLBA-112 active hydrogen maser frequency standards. These masers were manufactured for the National Radio Astronomy Observatory (NRAO) for use on the Very Long Baseline Array (VLBA) project and were furnished to the Jet Propulsion Laboratory (JPL) for the purpose of these tests. Tests on the two masers were performed in the JPL Frequency Standards Laboratory (FSL) and included the characterization of output frequency stability versus environmental factors such as temperature, humidity, magnetic field, and barometric pressure. The performance tests also included the determination of phase noise and Allan variance using both FSL and Sigma Tau masers as references. All tests were conducted under controlled laboratory conditions, with only the desired environmental and operational parameters varied to determine sensitivity to external environment.

  13. A shock-tube measurement of the SiO/E 1 Sigma + - X 1 Sigma +/ transition moment

    NASA Technical Reports Server (NTRS)

    Park, C.

    1978-01-01

    The sum of the squares of the electronic transition moments for the (E 1 Sigma +) - (X 1 Sigma +) band system of SiO has been determined from absorption measurements conducted in the reflected-shock region of a shock tube. The test gas produced by shock-heating a mixture of SiCl4, N2O, and Ar, and the spectra were recorded photographically in the 150-230-nm wavelength range. The values of the sum of the squares were determined by comparing the measured absorption spectra with those produced by a line-by-line synthetic spectrum calculation. The value so deduced at an r-centroid value of 3.0 bohr was 0.86 + or - 0.10 atomic unit.

  14. The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator.

    PubMed

    Fontanilla, Dominique; Johannessen, Molly; Hajipour, Abdol R; Cozzi, Nicholas V; Jackson, Meyer B; Ruoho, Arnold E

    2009-02-13

    The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor. PMID:19213917

  15. The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator

    PubMed Central

    Fontanilla, Dominique; Johannessen, Molly; Hajipour, Abdol R.; Cozzi, Nicholas V.; Jackson, Meyer B.; Ruoho, Arnold E.

    2010-01-01

    The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor. PMID:19213917

  16. Sigma: Strain-level inference of genomes from metagenomic analysis for biosurveillance

    SciTech Connect

    Ahn, Tae-Hyuk; Chai, Juanjuan; Pan, Chongle

    2014-09-29

    Motivation: Metagenomic sequencing of clinical samples provides a promising technique for direct pathogen detection and characterization in biosurveillance. Taxonomic analysis at the strain level can be used to resolve serotypes of a pathogen in biosurveillance. Sigma was developed for strain-level identification and quantification of pathogens using their reference genomes based on metagenomic analysis. Results: Sigma provides not only accurate strain-level inferences, but also three unique capabilities: (i) Sigma quantifies the statistical uncertainty of its inferences, which includes hypothesis testing of identified genomes and confidence interval estimation of their relative abundances; (ii) Sigma enables strain variant calling by assigning metagenomic reads to their most likely reference genomes; and (iii) Sigma supports parallel computing for fast analysis of large datasets. In conclusion, the algorithm performance was evaluated using simulated mock communities and fecal samples with spike-in pathogen strains. Availability and Implementation: Sigma was implemented in C++ with source codes and binaries freely available at http://sigma.omicsbio.org.

  17. Cold collisions of PH ({sup 3}{Sigma}{sup -}) with helium in magnetic fields

    SciTech Connect

    Feng, Eryin; Yu, Chunhua; Sun, Chunyan; Shao, Xi; Huang, Wuying

    2011-12-15

    A theoretical investigation of the He-PH ({sup 3}{Sigma}{sup -}) complex is presented. We perform ab initio calculations of the interaction potential energy surface and discuss its error bounds with relevance to cold collisions, and we carry out accurate calculations of bound energy levels of the complex including the molecular fine structure and magnetic-field effect. We find the potential has two shallow minima and supports ten and 13 bound levels in complex with {sup 3}He and {sup 4}He, respectively. Based on the potential the quantum scattering calculations are then implemented for elastic and inelastic cross sections of the magnetically trappable low-field-seeking state of PH ({sup 3}{Sigma}{sup -}) in collision with {sup 3}He atom. The cold-collision properties and the influence of the external magnetic field as well as the effect of the uncertainty of interaction potential on the collisionally induced Zeeman relaxation are explored and discussed in detail. The ratio of elastic to inelastic cross sections is large over a wide range of collision energy, magnetic field, and scaling factor of the potential, so that helium buffer-gas loading and evaporative cooling of PH is a good prospect.

  18. SEMICONDUCTOR INTEGRATED CIRCUITS: Improved low-distortion sigma-delta ADC with DWA for WLAN standards

    NASA Astrophysics Data System (ADS)

    Di, Li; Yintang, Yang; Zhangming, Zhu; Lichun, Shi; Xiaofeng, Wu; Jiangan, Wang

    2010-02-01

    An improved low distortion sigma-delta ADC (analog-to-digital converter) for wireless local area network standards is presented. A feed-forward MASH 2-2 multi-bit cascaded sigma-delta ADC is adopted; however, this work shows a much better performance than the ADCs which have been presented to date by adding a feedback factor in the second stage to improve the performance of the in-band SNDR (signal to noise and distortion ratio), using 4-bit ADCs in both stages to minimize the quantization noise. Data weighted averaging technology is therefore used to decrease the mismatch noise induced by the 4-bit DACs, which improves the SFDR (spurious free dynamic range) of the ADC. The modulator has been implemented by a 0.18 μm CMOS process and operates at a single 1.8 V supply voltage. Experimental results show that for a 1.25 MHz @ -6 dBFS input signal at 160 MHz sampling frequency, the improved ADC with all non-idealities considered achieves a peak SNDR of 80.9 dB and an SFDR of 87 dB, and the effective number of bits is 13.15 bits.

  19. Quasifree Lambda, Sigma^0, and Sigma^- electroproduction from 1,2H, 3,4He, and Carbon

    SciTech Connect

    F. Dohrmann; A. Ahmidouch; C.S. Armstrong; J. Arrington; R. Asaturyan; S. Avery; K. Bailey; H. Bitao; H. Breuer; D.S. Brown; R. Carlini; J. Cha; N. Chant; E. Christy; A. Cochran; L. Cole; J. Crowder; S. Danagoulian; M. Elaasar; R. Ent; H. Fenker; Y. Fujii; L. Gan; K. Garrow; D.F. Geesaman; P. Gueye; K. Hafidi; W. Hinton; H. Juengst; C. Keppel; Y. Liang; J.H. Liu; A. Lung; D. Mack; P. Markowitz; J. Mitchell; T. Miyoshi; H. Mkrtchyan; S.K. Mtingwa; B. Mueller; G. Niculescu; I. Niculescu; D. Potterveld; B.A. Raue; P.E. Reimer; J. Reinhold; J. Roche; M. Sarsour; Y. Sato; R.E. Segel; A. Semenov; S. Stepanyan; V. Tadevosyan; S. Tajima; L. Tang; A. Uzzle; S. Wood; H. Yamaguchi; C. Yan; L. Yuan; B. Zeidman; M. Zeier; B. Zihlmann

    2007-07-30

    Kaon electroproduction from light nuclei and hydrogen, using 1H, 2H, 3He, 4He, and Carbon targets has been measured at Jefferson Laboratory. The quasifree angular distributions of Lambda and Sigma hyperons were determined at Q^2= 0.35(GeV/c)^2 and W= 1.91GeV. Electroproduction on hydrogen was measured at the same kinematics for reference.

  20. Comparing Linear Sigma Model K-matrix studies of sigma/f0 and the Higgs boson

    SciTech Connect

    A. Abdel-Rehim; Deirdre M. Black; A.H. Fariborz; Salah Nasri; Joseph Schechter

    2003-05-01

    We present a description of the low energy pi pi scattering data using the Linear Sigma Model with K-matrix unitarization. Then we carry out an analogous study of the strongly-coupled minimal Higgs sector of the electroweak theory. We discuss the effect of the unitarization prescription on the WW or ZZ fusion processes and also suggest a related treatment for other Higgs production processes such as gluon fusion.

  1. Potential applications for sigma receptor ligands in cancer diagnosis and therapy.

    PubMed

    van Waarde, Aren; Rybczynska, Anna A; Ramakrishnan, Nisha K; Ishiwata, Kiichi; Elsinga, Philip H; Dierckx, Rudi A J O

    2015-10-01

    Sigma receptors (sigma-1 and sigma-2) represent two independent classes of proteins. Their endogenous ligands may include the hallucinogen N,N-dimethyltryptamine (DMT) and sphingolipid-derived amines which interact with sigma-1 receptors, besides steroid hormones (e.g., progesterone) which bind to both sigma receptor subpopulations. The sigma-1 receptor is a ligand-regulated molecular chaperone with various ion channels and G-protein-coupled membrane receptors as clients. The sigma-2 receptor was identified as the progesterone receptor membrane component 1 (PGRMC1). Although sigma receptors are over-expressed in tumors and up-regulated in rapidly dividing normal tissue, their ligands induce significant cell death only in tumor tissue. Sigma ligands may therefore be used to selectively eradicate tumors. Multiple mechanisms appear to underlie cell killing after administration of sigma ligands, and the signaling pathways are dependent both on the type of ligand and the type of tumor cell. Recent evidence suggests that the sigma-2 receptor is a potential tumor and serum biomarker for human lung cancer and an important target for inhibiting tumor invasion and cancer progression. Current radiochemical efforts are focused on the development of subtype-selective radioligands for positron emission tomography (PET) imaging. Right now, the mostpromising tracers are [18F]fluspidine and [18F]FTC-146 for sigma-1 receptors and [11C]RHM-1 and [18F]ISO-1 for the sigma-2 subtype. Nanoparticles coupled to sigma ligands have shown considerable potential for targeted delivery of antitumor drugs in animal models of cancer, but clinical studies exploring this strategy in cancer patients have not yet been reported. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. PMID:25173780

  2. Dicarbollylamine ligand as a tunable template for sigma,sigma- and pi,sigma-bonding modes: syntheses, structures, and theoretical studies of eta5:eta1-coordinated constrained-geometry group 13 metal complexes.

    PubMed

    Lee, Jong-Dae; Kim, Sung-Kwan; Kim, Tae-Jin; Han, Won-Sik; Lee, Young-Joo; Yoo, Dae-Hwan; Cheong, Minserk; Ko, Jaejung; Kang, Sang Ook

    2008-07-30

    A series of group 13 main group complexes with pi,sigma-type bonding interaction of the formula [{(eta (5)-RC 2B 9H 9)(CH 2)(eta (1)-NMe 2)}MMe] (M = Al, R = H 5, Me 6; Ga, R = H 7, Me 8; In, R = H 9, Me 10) was produced by the reaction of group 13 metal alkyls (MMe 3; M = Al, Ga, In) with the dicarbollylamine ligands, nido-8-R-7,8-C 2B 9H 10-7-(CH 2)NHMe 2 (R = H 1, Me 2). The reactions of 1 and 2 with AlMe 3 in toluene initially afforded tetra-coordinated aluminum complexes with sigma,sigma-type bonding interaction, [{(eta (1)-RC 2B 9H 10)(CH 2)(eta (1)-NMe 2)}AlMe 2] (R = H 3, Me 4), which readily underwent further methane elimination to yield the corresponding constrained geometry complexes (CGCs, 5 and 6) of aluminum with pi,sigma-bonding interaction. However, the reactions between 1 and 2 and MMe 3 (M = Ga, In) in toluene produced gallium and indium pi,sigma-CGCs of 7 and 10 directly, not proceeding through sigma,sigma-intermediates. The structures of group 13 metal CGCs were established by X-ray diffraction studies of 5, 6, and 8, which authenticated a characteristic eta (5):eta (1)-coordination mode of the dicarbollylamino ligand to the group 13 metals. A similar pi,sigma-bonding interaction was also established in ethylene-bridged dicarbollylethylamine series. Thus, aluminum pi,sigma-CGCs of dicarbollylethylamine, [{(eta (5)-RC 2B 9H 9)(CH 2) 2(eta (1)-NBz 2)}AlMe] (R = H 17, Me 18), were prepared by the trans-metalation of the [{(eta (5)-RC 2B 9H 9)(CH 2) 2(eta (1)-NBz 2)}Ti(NMe 2) 2] (R = H 15, Me 16) with AlMe 3. However, only sigma,sigma-bonded complexes of the formula [{(eta (1)-RC 2B 9H 9)(CH 2) 2(eta (1)-NBz 2)}AlMe 2] (R = H 13, Me 14) were isolated by the reaction between [ nido-7-8-R-7,8-C 2B 9H 10-(CH 2) 2HNBz 2] (R = H 11, Me 12) and AlMe 3. When methane-elimination reactions between metal alkyls and dicarbollylamines were carried out with either the gallium atom or monobenzyl aminoethyl tethered ligands, [ nido-7-H 2NBz(CH 2) 2-8-R-7,8-C 2B 9H

  3. Sigma-2 Receptors Play a Role in Cellular Metabolism: Stimulation of Glycolytic Hallmarks by CM764 in Human SK-N-SH Neuroblastoma.

    PubMed

    Nicholson, Hilary; Mesangeau, Christophe; McCurdy, Christopher R; Bowen, Wayne D

    2016-02-01

    Sigma-2 receptors are attractive antineoplastic targets due to their ability to induce apoptosis and their upregulation in rapidly proliferating cancer cells compared with healthy tissue. However, this role is inconsistent with overexpression in cancer, which is typically associated with upregulation of prosurvival factors. Here, we report a novel metabolic regulatory function for sigma-2 receptors. CM764 [6-acetyl-3-(4-(4-(2-amino-4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one] binds with Ki values of 86.6 ± 2.8 and 3.5 ± 0.9 nM at the sigma-1 and sigma-2 receptors, respectively. CM764 increased reduction of MTT [3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide] in human SK-N-SH neuroblastoma compared with untreated cells, an effect not due to proliferation. This effect was attenuated by five different sigma antagonists, including CM572 [3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)-6-isothiocyanatobenzo[d]oxazol-2(3H)-one], which has no significant affinity for sigma-1 receptors. This effect was also observed in MG-63 osteosarcoma and HEK293T cells, indicating that this function is not exclusive to neuroblastoma or to cancer cells. CM764 produced an immediate, robust, and transient increase in cytosolic calcium, consistent with sigma-2 receptor activation. Additionally, we observed an increase in the total NAD(+)/NADH level and the ATP level in CM764-treated SK-N-SH cells compared with untreated cells. After only 4 hours of treatment, basal levels of reactive oxygen species were reduced by 90% in cells treated with CM764 over untreated cells, and HIF1α and VEGF levels were increased after 3-24 hours of treatment. These data indicate that sigma-2 receptors may play a role in induction of glycolysis, representing a possible prosurvival function for the sigma-2 receptor that is consistent with its upregulation in cancer cells compared with healthy tissue. PMID:26574517

  4. Allosteric modulation of ligand binding to [3H](+)pentazocine-defined sigma recognition sites by phenytoin.

    PubMed

    DeHaven-Hudkins, D L; Ford-Rice, F Y; Allen, J T; Hudkins, R L

    1993-01-01

    The allosteric modulation of sigma recognition sites by phenytoin (diphenylhydantoin) has been demonstrated by the ability of phenytoin to stimulate binding of various [3H] sigma ligands, as well as to slow dissociation from sigma sites and to shift sigma sites from a low- to a high-affinity state. Phenytoin stimulated the binding of the sigma 1- selective ligand [3H](+)pentazocine in a dose-dependent manner. Stimulation of binding at a final concentration of 250 microM phenytoin was associated with a decrease in the KD. The affinities of the sigma reference compounds caramiphen, dextromethorphan, dextrophan, (+)3-PPP and (+)SKF-10,047 were three- to eight-fold higher, while the affinities of benzetimide, BMY-14802, carbetapentane, DTG and haloperidol were unchanged in the presence of 250 microM phenytoin. The relative sensitivity of sigma compounds to allosteric modulation by phenytoin is not a property of all sigma ligands, and may provide an in vitro basis for distinguishing actions of sigma compounds and predicting sigma effects in vivo. PMID:8515681

  5. Characterization of 4-Nitrophenylpropyl-N-alkylamine Interactions with Sigma Receptors

    PubMed Central

    Chu, Uyen B.; Hajipour, Abdol R.; Ramachandran, Subramaniam; Ruoho, Arnold E.

    2011-01-01

    Sigma receptors are small membrane proteins implicated in a number of pathophysiological conditions including drug addiction, psychosis and cancer; thus, small molecule inhibitors of sigma receptors have been proposed as potential pharmacotherapeutics for these diseases. We previously discovered that endogenous monochain N-alkyl sphingolipids including D-erythro-sphingosine, sphinganine, and N,N-dimethyl sphingosine bind to the sigma-1 receptor at physiologically relevant concentrations [Ramachandran et al. 2009 Eur J Pharmacol. 609(1–3):19–26]. Here, we investigated several N-alkylamines of varying chain lengths as sigma receptor ligands. Although the KI values for N-alkylamines were found to be in the micromolar range, when N-3-phenylpropyl and N-3-(4-nitrophenyl)propyl derivatives of butyl- (1a and 1b), heptyl- (2a and 2b), dodecyl- (3a and 3b), and octadecyl-amine (4a and 4b) were evaluated as sigma receptor ligands we found that these compounds exhibited nanomolar affinities with both sigma-1 and sigma-2 receptors. A screen of the high affinity ligands 2a, 2b, 3a and 3b against a variety of other receptors/transporters confirmed these four compounds to be highly selective mixed sigma-1 and sigma-2 ligands. Additionally, in HEK293 cells reconstituted with Kv1.4 potassium channel and the sigma-1 receptor, these derivatives were able to inhibit the outward current from the channel – consistent with sigma receptor modulation. Finally, cytotoxicity assays showed that 2a, 2b, 3a and 3b were highly potent against a number of cancer cell lines, demonstrating their potential utility as mixed sigma-1 and sigma-2 receptor anti-cancer agents. PMID:21790129

  6. Development and initial test of the University of Wisconsin global isentropic-sigma model

    NASA Technical Reports Server (NTRS)

    Zapotocny, Tom H.; Johnson, Donald R.; Reames, Fred M.

    1994-01-01

    The description of a global version of the University of Wisconsin (UW) hybrid isentropic-sigma (theta-sigma) model and the results from an initial numerical weather prediction experiment are presented in this paper. The main objectives of this initial test are to (1) discuss theta-sigma model development and computer requirements, (2) demonstrate the ability of the UW theta-sigma model for global numerical weather prediction using realistic orography and parameterized physical processes, and (3) compare the transport of an inert trace constituent against a nominally 'identical' sigma coordinate model. Initial and verifying data for the 5-day simulations presented in this work were supplied by the Goddard Earth Observing System (GEOS-1) data assimilation system. The time period studied is 1-6 February 1985. This validation experiment demonstrates that the global UW theta-sigma model produces a realistic 5-day simulation of the mass and momentum distributions when compared to both the identical sigma model and GEOS-1 verification. Root-mean-square errors demonstrate that the theta-sigma model is slightly more accurate than the nominally identical sigma model with respect to standard synoptic variables. Of particular importance, the UW theta-sigma model displays a distinct advantage over the conventional sigma model with respect to the prognostic simulation of inert trace constituent transport in amplifying baroclinic waves of the extratropics. This is especially true in the upper troposphere and stratosphere where the spatial integrity and conservation of an inert trace constituent is severely compromised in the sigma model compared to the theta-sigma model.

  7. Using Six Sigma to improve the film library.

    PubMed

    Benedetto, Anthony R; Dunnington, Joel S; Oxford-Zelenske, Deborah

    2002-01-01

    The film library of a film-based radiology department is a mission-critical component of the department that is frequently underappreciated and under-staffed. A poorly performing film library causes operational problems for not only the radiology department, but for the institution as a whole. Since Six Sigma techniques had proved successful in an earlier CT throughput improvement project, the University of Texas M.D. Anderson Cancer Center Division of Diagnostic Imaging decided to use Six Sigma techniques to dramatically improve the performance of its film library. Nine mini-project teams were formed to address the basic operating functions of the film library. The teams included film library employees, employees from other sections of radiology, employees from stakeholders outside of radiology, and radiologists and referring physicians, as appropriate to the team's mission. Each Six Sigma team developed a process map of the current process, reviewed or acquired baseline quantitative data to assess the current level of performance, and then modified the process map to incorporate their recommendations for improving the process. An overall project steering committee reviewed recommendations from each Six Sigma team to assure that all of the teams' efforts were coordinated and aligned with the overall project goals. The steering committee also provided advice on implementation strategies, particularly for changes that would have an immediate effect on stakeholders outside of the radiology department. After implementation of recommendations, quantitative data were collected again to determine if the changes were having the desired effect. Improvement in both quantitative metrics and in employee morale have been experienced. We continue to collect data as assurance that the improvements are being sustained over the long haul. Six Sigma techniques, which are as quantitatively-based as possible, are useful in a service-oriented organization, such as a film library. The

  8. O(N) Generalized nonlinear sigma model and its applications

    SciTech Connect

    Ferrari, F. Paturej, J.; Vilgis, T. A.

    2010-02-15

    In this work the results of an interdisciplinary research between field theory and statistical mechanics will be presented. It is shown that the dynamics of an inextensible chain is described by a slight generalization of the O(d) nonlinear sigma model. It is checked, that in the large time limit the correct equilibrium distribution is reached. Our approach is based on path integrals, but it may be also connected to the usual description of the dynamics of a chain as a diffusion stochastic process. Some applications of our results will be discussed, like for instance the calculation of the average distance between two polymer segments.

  9. Spectra of sigma models on semi-symmetric spaces

    NASA Astrophysics Data System (ADS)

    Cagnazzo, Alessandra; Schomerus, Volker; Tlapak, Vaclav

    2016-05-01

    Sigma models on semi-symmetric spaces provide the central building block for string theories on AdS backgrounds. Under certain conditions on the global supersymmetry group they can be made one-loop conformal by adding an appropriate fermionic Wess-Zumino term. We determine the full one-loop dilation operator of the theory. It involves an interesting new XXZ-like interaction term. Eigenvalues of our dilation operator, i.e. the one-loop anomalous dimensions, are computed for a few examples.

  10. A review of sigma models for quantum chaotic dynamics

    NASA Astrophysics Data System (ADS)

    Altland, Alexander; Gnutzmann, Sven; Haake, Fritz; Micklitz, Tobias

    2015-07-01

    We review the construction of the supersymmetric sigma model for unitary maps, using the color-flavor transformation. We then illustrate applications by three case studies in quantum chaos. In two of these cases, general Floquet maps and quantum graphs, we show that universal spectral fluctuations arise provided the pertinent classical dynamics are fully chaotic (ergodic and with decay rates sufficiently gapped away from zero). In the third case, the kicked rotor, we show how the existence of arbitrarily long-lived modes of excitation (diffusion) precludes universal fluctuations and entails quantum localization.

  11. Modeling hybrid stars with an SU(3) nonlinear {sigma} model

    SciTech Connect

    Negreiros, Rodrigo; Dexheimer, V. A.; Schramm, S.

    2010-09-15

    We study the behavior of hybrid stars by using an extended hadronic and quark SU(3) nonlinear sigma model. The degrees of freedom change naturally, in this model, from hadrons to quarks as the density/temperature increases. At zero temperature, we reproduce massive neutron stars, which contain cores of hybrid matter of 2 km for the nonrotating case and 1.18 and 0.87 km, in the equatorial and polar directions, respectively, for stars that rotate at the Kepler frequency (physical cases lie in between). The cooling of such stars is also analyzed.

  12. A review of sigma models for quantum chaotic dynamics.

    PubMed

    Altland, Alexander; Gnutzmann, Sven; Haake, Fritz; Micklitz, Tobias

    2015-07-01

    We review the construction of the supersymmetric sigma model for unitary maps, using the color-flavor transformation. We then illustrate applications by three case studies in quantum chaos. In two of these cases, general Floquet maps and quantum graphs, we show that universal spectral fluctuations arise provided the pertinent classical dynamics are fully chaotic (ergodic and with decay rates sufficiently gapped away from zero). In the third case, the kicked rotor, we show how the existence of arbitrarily long-lived modes of excitation (diffusion) precludes universal fluctuations and entails quantum localization. PMID:26181515

  13. Six Sigma in health care management and strategy.

    PubMed

    Carrigan, Martin D; Kujawa, David

    2006-01-01

    In the years ahead, health care organizations will continue to face numerous challenges from longstanding and currently unresolved issues and new and emerging trends. Some of these include workforce shortages, rising consumerism, patient and stakeholder expectations, quality and patient safety, reimbursement, an aging population, regulatory constraints, and disaster preparedness. Health care organizations will need to adopt effective strategic tools, such as Six Sigma, to improve efficiency and effectiveness. Failure to do so will not only threaten their ability to remain competitive and provide quality care to the communities they serve, but their own survival will also be jeopardized by shrinking margins caused by continued downward pressure on reimbursement. PMID:16699328

  14. The Sigma-1 Receptor as a Pluripotent Modulator in Living Systems.

    PubMed

    Su, Tsung-Ping; Su, Tzu-Chieh; Nakamura, Yoki; Tsai, Shang-Yi

    2016-04-01

    The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum (ER) protein that resides specifically in the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), an interface between ER and mitochondria. In addition to being able to translocate to the plasma membrane (PM) to interact with ion channels and other receptors, Sig-1R also occurs at the nuclear envelope, where it recruits chromatin-remodeling factors to affect the transcription of genes. Sig-1Rs have also been reported to interact with other membranous or soluble proteins at other loci, including the cytosol, and to be involved in several central nervous system (CNS) diseases. Here, we propose that Sig-1R is a pluripotent modulator with resultant multiple functional manifestations in living systems. PMID:26869505

  15. Sigma elements are position-specific for many different yeast tRNA genes.

    PubMed Central

    Sandmeyer, S B; Bilanchone, V W; Clark, D J; Morcos, P; Carle, G F; Brodeur, G M

    1988-01-01

    We determined the DNA sequence of seventeen sigma elements and flanking regions in order to investigate the extent of the association between the yeast repetitive element, sigma, and tRNA genes. Fifteen of seventeen sigma elements analyzed begin at position -19 to -16 with respect to the 5' end of a tRNA-coding sequence. This region is close to the initiation point of tRNA gene transcription and contains a sequence which is modestly conserved for a number of tRNA genes. Two pairs of identical sigma elements occur as the long terminal repeats of a sequence which, together with flanking sigma elements, has the structural properties of a retrotransposon; this element has been named Ty3 (manuscript submitted). Hybridization analysis of yeast chromosomal DNA separated by orthogonal field alternation gel electrophoresis (OFAGE) showed that Ty3 and isolated sigma elements are distributed over many chromosomes in the yeast genome. Images PMID:3279393

  16. Nonlinear sigma models with compact hyperbolic target spaces

    NASA Astrophysics Data System (ADS)

    Gubser, Steven; Saleem, Zain H.; Schoenholz, Samuel S.; Stoica, Bogdan; Stokes, James

    2016-06-01

    We explore the phase structure of nonlinear sigma models with target spaces corresponding to compact quotients of hyperbolic space, focusing on the case of a hyperbolic genus-2 Riemann surface. The continuum theory of these models can be approximated by a lattice spin system which we simulate using Monte Carlo methods. The target space possesses interesting geometric and topological properties which are reflected in novel features of the sigma model. In particular, we observe a topological phase transition at a critical temperature, above which vortices proliferate, reminiscent of the Kosterlitz-Thouless phase transition in the O(2) model [1, 2]. Unlike in the O(2) case, there are many different types of vortices, suggesting a possible analogy to the Hagedorn treatment of statistical mechanics of a proliferating number of hadron species. Below the critical temperature the spins cluster around six special points in the target space known as Weierstrass points. The diversity of compact hyperbolic manifolds suggests that our model is only the simplest example of a broad class of statistical mechanical models whose main features can be understood essentially in geometric terms.

  17. Accurate estimation of sigma(exp 0) using AIRSAR data

    NASA Technical Reports Server (NTRS)

    Holecz, Francesco; Rignot, Eric

    1995-01-01

    During recent years signature analysis, classification, and modeling of Synthetic Aperture Radar (SAR) data as well as estimation of geophysical parameters from SAR data have received a great deal of interest. An important requirement for the quantitative use of SAR data is the accurate estimation of the backscattering coefficient sigma(exp 0). In terrain with relief variations radar signals are distorted due to the projection of the scene topography into the slant range-Doppler plane. The effect of these variations is to change the physical size of the scattering area, leading to errors in the radar backscatter values and incidence angle. For this reason the local incidence angle, derived from sensor position and Digital Elevation Model (DEM) data must always be considered. Especially in the airborne case, the antenna gain pattern can be an additional source of radiometric error, because the radar look angle is not known precisely as a result of the the aircraft motions and the local surface topography. Consequently, radiometric distortions due to the antenna gain pattern must also be corrected for each resolution cell, by taking into account aircraft displacements (position and attitude) and position of the backscatter element, defined by the DEM data. In this paper, a method to derive an accurate estimation of the backscattering coefficient using NASA/JPL AIRSAR data is presented. The results are evaluated in terms of geometric accuracy, radiometric variations of sigma(exp 0), and precision of the estimated forest biomass.

  18. Non-linear sigma-models and string theories

    SciTech Connect

    Sen, A.

    1986-10-01

    The connection between sigma-models and string theories is discussed, as well as how the sigma-models can be used as tools to prove various results in string theories. Closed bosonic string theory in the light cone gauge is very briefly introduced. Then, closed bosonic string theory in the presence of massless background fields is discussed. The light cone gauge is used, and it is shown that in order to obtain a Lorentz invariant theory, the string theory in the presence of background fields must be described by a two-dimensional conformally invariant theory. The resulting constraints on the background fields are found to be the equations of motion of the string theory. The analysis is extended to the case of the heterotic string theory and the superstring theory in the presence of the massless background fields. It is then shown how to use these results to obtain nontrivial solutions to the string field equations. Another application of these results is shown, namely to prove that the effective cosmological constant after compactification vanishes as a consequence of the classical equations of motion of the string theory. 34 refs. (LEW)

  19. Roles of sigma-1 receptors in Alzheimer’s disease

    PubMed Central

    Jin, Jia-Li; Fang, Min; Zhao, Yan-Xin; Liu, Xue-Yuan

    2015-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of senile dementia all over the world. Still no existing drugs can effectively reverse the cognitive impairment. However, Sigma-1 (σ-1) receptors have been long implicated in multiple neurological and psychiatric conditions over these years. In this review, we discuss the current understanding of σ-1 receptor functions. Through regulation of lipid rafts, secretases, kinases, neuroceptors and ion channels, σ-1 receptors can influence cellular signal transduction, TCA cycle, oxidative stress, neuron plasticity and neurotransmitter release etc. Based on this, we suggest the key cellular mechanisms linking σ-1 receptor to Alzheimer’s disease. Besides, we detail the evidences showing that σ-1 receptors agonists, being the promising compounds for treatment of cognitive dysfunction, exhibit robust neuroprotection and anti-amnesia effect against Aβ neurotoxicity in the progress of Alzheimer’s disease. The evidence comes from animal models, preclinical studies in humans and full clinical trials. In addition, the questions to be solved regarding this receptor are also presented. When concerned with NMDAR, σ-1 receptor activation may result in two totally different influences on AD. Utilization of σ-1 agents early in AD remains an overlooked therapeutic opportunity. This article may pave the way for further studies about sigma-1 receptor on Alzheimer’s disease. PMID:26131055

  20. Roles of sigma-1 receptors in Alzheimer's disease.

    PubMed

    Jin, Jia-Li; Fang, Min; Zhao, Yan-Xin; Liu, Xue-Yuan

    2015-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of senile dementia all over the world. Still no existing drugs can effectively reverse the cognitive impairment. However, Sigma-1 (σ-1) receptors have been long implicated in multiple neurological and psychiatric conditions over these years. In this review, we discuss the current understanding of σ-1 receptor functions. Through regulation of lipid rafts, secretases, kinases, neuroceptors and ion channels, σ-1 receptors can influence cellular signal transduction, TCA cycle, oxidative stress, neuron plasticity and neurotransmitter release etc. Based on this, we suggest the key cellular mechanisms linking σ-1 receptor to Alzheimer's disease. Besides, we detail the evidences showing that σ-1 receptors agonists, being the promising compounds for treatment of cognitive dysfunction, exhibit robust neuroprotection and anti-amnesia effect against Aβ neurotoxicity in the progress of Alzheimer's disease. The evidence comes from animal models, preclinical studies in humans and full clinical trials. In addition, the questions to be solved regarding this receptor are also presented. When concerned with NMDAR, σ-1 receptor activation may result in two totally different influences on AD. Utilization of σ-1 agents early in AD remains an overlooked therapeutic opportunity. This article may pave the way for further studies about sigma-1 receptor on Alzheimer's disease. PMID:26131055

  1. Binding of kappa- and sigma-opiates in rat brain

    SciTech Connect

    Wolozin, B.L.; Nishimura, S.; Pasternak, G.W.

    1982-06-01

    Detailed displacements of (/sup 3/H)dihydromorphine by ketocyclazocine and SKF 10,047, (/sup 3/H)ethylketocyclazocine by SKF 10,047, and (/sup 3/H)SKF 10,047 by ketocyclazocine are all multiphasic, suggesting multiple binding sites. After treating brain tissue in vitro with naloxazone, all displacements lose the initial inhibition of /sup 3/H-ligand binding by low concentrations of unlabeled drugs. Together with Scatchard analysis of saturation experiments, these studies suggest a common site which binds mu-, kappa, and sigma-opiates and enkephalins equally well and with highest affinity (KD less than 1 nM). The ability of unlabeled drugs to displace the low affinity binding of (/sup 3/H)dihydromorphine (KD . 3 nM), (/sup 3/H)ethylketocyclazocine (KD . 4 nM), (/sup 3/H)SKF 10,047 (KD . 6 nM), and D-Ala2-D-Leu5-(/sup 3/H)enkephalin (KD . 5 nM) remaining after treating tissue with naloxazone demonstrates unique pharmacological profiles for each. These results suggest the existence of distinct binding sites for kappa- and sigma-opiates which differ from those sites which selectively bind morphine (mu) and enkephalin (delta).

  2. Solution to the Sigma Problem of Pulsar Wind Nebulae

    NASA Astrophysics Data System (ADS)

    Porth, Oliver; Komissarov, Serguei S.; Keppens, Rony

    2014-03-01

    Pulsar wind nebulae (PWN) provide a unique test-bed for the study of highly relativistic processes right at our astronomical doorstep. In this contribution we will show results from the first 3D RMHD simulations of PWN. Of key interest to our study is the long standing "sigma-problem" that challenges MHD models of Pulsars and their nebulae now for 3 decades. Earlier 2D MHD models were very successful in reproducing the morphology of the inner Crab nebula showing a jet, torus, concentric wisps and a variable knot. However, these models are limited to a purely toroidal field geometry which leads to an exaggerated compression of the termination shock and polar jet — in contrast to the observations. In three dimensions, the toroidal field structure is susceptible to current driven instabilities; hence kink instability and magnetic dissipation govern the dynamics of the nebula flow. This leads to a resolution of the sigma-problem once also the pulsar's obliqueness (striped wind) is taken into account. In addition, we present polarized synchrotron maps constructed from the 3D simulations, showing the wealth of morphological features reproduced in 2D is preserved in the 3D case.

  3. Existence of vortices in a self-dual gauged linear sigma model and its singular limit

    NASA Astrophysics Data System (ADS)

    Kim, Namkwon

    2006-03-01

    We study rigorously the static (2 + 1)D gauged linear sigma model introduced by Schroers. Analysing the governing system of partial differential equations, we show the existence of energy finite vortices under the partially broken symmetry on R2 with some conditions consistent with the necessary conditions given by Yang. Also, with a special choice of representation, we show that the gauged O(3) sigma model is a singular limit of the gauged linear sigma model.

  4. [Physiological functions of sigma-1 receptors and its relation to psychic dependence].

    PubMed

    Mori, Tomohisa; Yoshizawa, Kazumi; Shibasaki, Masahiro; Suzuki, Tsutomu

    2012-12-01

    Sigma-1 receptors had been believed as a one of the opioid receptors. Recent reports have demonstrated that the sigma-1 receptor is a nonopioid receptor that resides specifically at the endoplasmic reticulum (ER)-mitochondrion interface and has been shown to be protective against neurodegeneration as an ER chaperone. In this review, we review the molecular mechanism on the cytoprotective effects of sigma-1 receptors. Furthermore, we summarize the effects of sigma-1 receptor ligand on the behavioral effects, especially on the reward-related behaviors induced by psychostimulants. The ER is a major locus for the synthesis of proteins. Under physiological conditions, the overall protein level in the ER is maintained by a balance between the protein synthesis and degradation. When the balance is perturbed, signaling pathways (the unfolded protein response (UPR) caused by ER stress or the ER overload response (EOR)) are activated to regulate the cell survival/death signalings. Sigma-1 receptor could be upregulated by ER stress and EOR, and that upregulated sigma-1 receptors attenuate UPR and EOR by increasing the chaperone activity of sigma-1 receptors and attenuation of prossessed NF-kappaB activity, respectively. On the other hand, even sigma-1 receptor could be upregulated by self-administration of methamphetamine in the ventral tegmental area, exact mechanism how sigma-1 receptor chaperone affect the behavioral effects induced by psychostimulants is not yet cleared. However, the prototypic sigma-1 receptor agonist SKF10,047 induces psychotomimetic effects, and psychotomimetic-like discriminative stimulus effects are at least in part mediated by sigma-1 receptors. Recent research showed that endogenous hallucinogen (N,N-dimethyltryptamine) might be a sigma-1 receptor regulator, indicating that sigma-1 receptor is crosely related to psychotomimetic effects. Furthermore, sigma-1 receptor agonist can enhance the discriminative stimulus effects of psychostimulants, and

  5. Prioritizing risk analysis quality control plans based on Sigma-metrics.

    PubMed

    Westgard, Sten

    2013-03-01

    Six Sigma provides data-driven techniques that can enhance and improve the EP23 risk management approach for formulating quality control (QC) Plans. Risk analysis has significant drawbacks in its ability to identify and appropriately prioritize hazards and failure modes for mitigation of risks. Six Sigma quality management is inherently risk oriented on the basis of the required tolerance limits that define defective products. Six Sigma QC tools provide a quantitative assessment of method performance and an objective selection/design of statistical QC procedures. Furthermore, the observed sigma performance of a method is useful for prioritizing the need for development of QC plans. PMID:23331728

  6. Ab initio studies of low-lying 3Sigma(-), 3Pi, and 5Sigma(-) states of NH. I - Potential curves and dipole moment functions

    NASA Technical Reports Server (NTRS)

    Goldfield, Evelyn M.; Kirby, Kate P.

    1987-01-01

    Configuration interaction wave functions, potential energy curves, and dipole moment functions have been calculated for the four lowest 3Sigma(-) and the three lowest 3Pi states and 5Sigma(-) states of NH. The electronic wave functions were constructed to give a balanced description of valence-Rydberg interactions. Two repulsive states have been identified as important photodissociation pathways. Spectroscopic constants are presented for the bound states, and results are compared to other theoretical and experimental work. The possible predissociation of the A 3Pi state by the 1 5Sigma(-) state is discussed.

  7. On the A-dependence of {sigma}{sub L}/{sigma}{sub T}: Skeletons in the shadow

    SciTech Connect

    Milana, J.

    1994-04-01

    A most counter-intuitive dependence in the differential cross-section in the shadowing regime is shown to result from a higher-twist nuclear enhancement in R = {sigma}{sub L}/{sigma}{sub T} which severely complicates the unravelling from present data the corresponding dependence in Q{sup 2} of the nuclear structure functions, F{sub 2}{sup A}(x,Q{sup 2}). Indeed, until precision measurements close this loophole, the extrapolations of the structure functions to either higher Q{sup 2} or other processes (as is necessary to address present data at FNAL or future experiments at RHIC) must be considered problematic. The contribution CEBAF can make in this regard by providing systematic determination of R{sub A}(x, Q{sup 2}) is thus emphasized. The purpose of this talk is to motivate an experiment CEBAF can and should do, especially if upgraded to higher energies. While providing information on nuclear structure that is interesting in itself, the added motivation is that precision results will have important impact on other high-energy experiments involving nuclear targets that have been, and will continue to be done all over the world.

  8. THE L-{sigma} RELATION OF LOCAL H II GALAXIES

    SciTech Connect

    Bordalo, V.; Telles, E. E-mail: etelles@on.br

    2011-07-01

    For the first time we present a new data set of emission line widths for 118 star-forming regions in H II galaxies (HIIGs). This homogeneous set is used to investigate the L-{sigma} relation in conjunction with optical spectrophotometric observations. We were able to classify their nebular emission line profiles due to our high-resolution spectra. Peculiarities in the line profiles such as sharp lines, wings, asymmetries, and in some cases more than one component in emission were verified. From a new independent homogeneous set of spectrophotometric data, we derived physical condition parameters and performed statistical principal component analysis. We have investigated the potential role of metallicity (O/H), H{beta} equivalent width (W{sub H{beta}}), and ionization ratio [O III]/[O II] to account for the observational scatter of the L-{sigma} relation. Our results indicate that the L-{sigma} relation for HIIGs is more sensitive to the evolution of the current starburst event (short-term evolution) and dated by W{sub H}{beta} or even the [O III]/[O II] ratio. The long-term evolution measured by O/H also plays a potential role in determining the luminosity of the current burst for a given velocity dispersion and age as previously suggested. Additionally, galaxies showing Gaussian line profiles present tighter correlations indicating that they are the best targets for the application of the parametric relations as an extragalactic cosmological distance indicator. Best fits for a restricted homogeneous sample of 45 HIIGs provide us with a set of new extragalactic distance indicators with an rms scatter compatible with observational errors of {delta}log L{sub H}{alpha} = 0.2 dex or 0.5 mag. Improvements may still come from future optimized observational programs to reduce the observational uncertainties on the predicted luminosities of HIIGs in order to achieve the precision required for the application of these relations as tests of cosmological models.

  9. Endogenous digitalis-like factors: an overview of the history.

    PubMed

    Buckalew, Vardaman M

    2015-01-01

    The sodium pump is a ubiquitous cell surface enzyme, a Na, K ATPase, which maintains ion gradients between cells and the extracellular fluid (ECF). The extracellular domain of this enzyme contains a highly conserved binding site, a receptor for a plant derived family of compounds, the digitalis glycosides. These compounds inhibit the enzyme and are used in the treatment of congestive heart failure and certain cardiac arrhythmias. The highly conserved nature of this enzyme and its digitalis receptor led to early suggestions that endogenous regulators might exist. Recent examination of this hypothesis emerged from research in two separate areas: the regulation of ECF volume by a natriuretic hormone (NH), and the regulation of peripheral vascular resistance by a circulating inhibitor of vascular Na, K ATPase. These two areas merged with the hypothesis that NH and the vascular Na, K ATPase inhibitor were in fact the same entity, and that it played a causative role in the pathophysiology of certain types of hypertension. The possibility that multiple endogenous digitalis-like factors (EDLFs) exist emerged from efforts to characterize the circulating enzyme inhibitory activity. In this review, the development of this field from its beginnings is traced, the current status of the structure of EDLFs is briefly discussed, and areas for future development are suggested. PMID:25918512

  10. A simple predictive model of chemical potentials: H sub 2 ( sup 1. Sigma. sub g ) and Li sub 2 ( sup 1. Sigma. sub g )

    SciTech Connect

    Tang, K.T.; Toennies, J.P. ); Meyer, W. )

    1991-07-15

    A simple model for van der Waals potentials presented earlier (J. Chem. Phys. {bold 80}, 3726 (1984)) has been extended to describe chemical bonds by including the exchange-dispersion term of Herring and Flicker. For H{sub 2}, the {sup 1}{Sigma} ground state potential is predicted in excellent agreement with the accurately known {ital ab} {ital initio} potential, the well depth being reproduced to within 0.6%. New two configuration self-consistent-field (SCF) calculations for the {sup 1}{Sigma} and the {sup 3}{Sigma} states of Li{sub 2} have made it possible to test the model for this system as well. Here the discrepancy is only 3% in the well depth for the {sup 1}{Sigma} Li{sub 2} potential.

  11. The /A 1 Sigma +/ - /X 1 Sigma +/ system of the isotopic lithium hydrides - The molecular constants, potential energy curves, and their adiabatic corrections

    NASA Technical Reports Server (NTRS)

    Vidal, C. R.; Stwalley, W. C.

    1982-01-01

    The molecular constants and their adiabatic corrections have been determined for the (A 1 Sigma +) - (X 1 Sigma +) system of the isotopic lithium hydrides: (Li-6)H, (Li-7)H, (Li-6)D, and (Li-7)D. Using a fully quantum mechanical variational method, the potential energy curves (IPA potentials) are determined. Extending the variational method, we have obtained for the first time adiabatic corrections of potential energy curves from isotopic spectroscopic data. A significant difference between the potential energy curves of the lithium hydrides and the lithium deuterides has been observed. When Li-6 was replaced by Li-7, a significant difference was only observed for the (A 1 Sigma +) state, but not for the (X 1 Sigma +) state.

  12. Dipole moments and transition probabilities of the a 3Sigma(+)g - b 3Sigma(+)u system of molecular hydrogen

    NASA Technical Reports Server (NTRS)

    Guberman, S.; Dalgarno, A.; Posen, A.; Kwok, T. L.

    1986-01-01

    Multiconfiguration variational calculations of the electronic wave functions of the a 3Sigma(+)g and b 3Sigma(+)u states of molecular hydrogen are presented, and the electric dipole transition moment between them (of interest in connection with stellar atmospheres and the UV spectrum of the Jovian planets) is obtained. The dipole moment is used to calculate the probabilities of radiative transitions from the discrete vibrational levels of the a 3Sigma(+)g state to the vibrational continuum of the repulsive b 3Sigma(+)u state as functions of the wavelength of the emitted photons. The total transition probabilities and radiative lifetimes of the levels v prime = 0-20 are presented.

  13. A gene at 333 degrees on the Bacillus subtilis chromosome encodes the newly identified sigma B-dependent general stress protein GspA.

    PubMed Central

    Antelmann, H; Bernhardt, J; Schmid, R; Hecker, M

    1995-01-01

    In Bacillus subtilis, general stress proteins (Gsps) are induced in response to different stresses (heat, salt, or ethanol) or after nutrient starvation. The majority of the genes for the Gsps are organized in a very large stationary-phase or stress regulon which is controlled by alternative sigma factor sigma B. The most striking spots on Coomassie-stained two-dimensional gels belong to GsiB and GspA, which are synthesized at extremely high levels in response to different stresses. Therefore, we determined the N-terminal protein sequence of GspA, which exhibited total identity to a hypothetical 33.5-kDa protein of B. subtilis encoded by open reading frame 2 (ipa-12d) in the sacY-tyrS1 intergenic region. The GspA-encoding gene gspA and the upstream and downstream regions were cloned with the aid of the PCR technique. By primer extension experiments, one sigma B-dependent promoter immediately upstream of the coding region was identified. A putative factor-independent terminator closely followed the coding region. By Northern (RNA) blot analysis, a 0.95-kb transcript was detected which indicates a monocistronic transcriptional unit. The gspA mRNA was strongly induced by different stimuli like heat or salt stress and starvation for glucose. Analysis of RNA isolated from a sigma B deletion mutant revealed that the transcription of gspA is sigma B dependent. Insertional inactivation of the B. subtilis chromosomal gspA gene confirmed that the gspA gene is not essential for either vegetative growth or growth under the influence of different stresses. In gspA mutant cells, the level of flagellin was increased severalfold over that in wild-type cells. PMID:7768864

  14. Lean Six Sigma Application in Rear Combination Automotive Lighting Process

    NASA Astrophysics Data System (ADS)

    Sodkomkham, Thanwarhat; Chutima, Parames

    2016-05-01

    The case study company produces various front and rear lightings for automobiles and motorcycles. Currently, it faces two problems, i.e. high defective rate and high inventory. Lean Six Sigma was applied as a tool to solve the first problem, whereas the other problem was managed by changing the production concept from push to pull. The results showed that after applying all new settings to the process, the defect rate was reduced from 36,361 DPPM to 3,029 DPPM. In addition, after the implementation of the Kanban system, the company achieved substantial improvement in lead time reduction by 44%, in-process inventory reduction by 42%, finished good inventory reduction by 50%, and finished good area increased by 16%.

  15. Bethe ansatz for a quantum supercoset sigma model

    SciTech Connect

    Mann, Nelia; Polchinski, Joseph

    2005-10-15

    We study an integrable conformal OSp(2m+2|2m) supercoset model as an analog to the AdS{sub 5}xS{sup 5} superstring world-sheet theory. Using the known S-matrix for this system, we obtain integral equations for states of large particle number in an SU(2) sector, which are exact in the sigma model coupling constant. As a check, we derive as a limit the general classical Bethe equation of Kazakov, Marshakov, Minahan, and Zarembo. There are two distinct quantum expansions around the well-studied classical limit, the {lambda}{sup -1/2} effects and the 1/J effects. Our approach captures the first type, but not the second.

  16. Reservoir continuous process improvement six sigma methodology implementation

    SciTech Connect

    Wannamaker, A.L.

    1996-12-01

    The six sigma methodology adopted by AlliedSignal Inc. for implementing continuous improvement activity was applied to a new manufacturing assignment for Federal Manufacturing & Technologies (FM&T). The responsibility for reservoir development/production was transferred from Rocky Flats to FM&T. Pressure vessel fabrication was new to this facility. No fabrication history for this type of product existed in-house. Statistical tools such as process mapping, failure mode and effects analysis, and design of experiments were used to define and fully characterize the machine processes to be used in reservoir production. Continuous improvement with regard to operating efficiencies and product quality is an ongoing activity at FM&T.

  17. Hybridization of a sigma-delta-based CMOS hybrid detector

    NASA Astrophysics Data System (ADS)

    Kolb, K. E.; Stoffel, N. C.; Douglas, B.; Maloney, C. W.; Raisanen, A. D.; Ashe, B.; Figer, D. F.; Tamagawa, T.; Halpern, B.; Ignjatovic, Zeljko

    2010-07-01

    The Rochester Imaging Detector Laboratory, University of Rochester, Infotonics Technology Center, and Jet Process Corporation developed a hybrid silicon detector with an on-chip sigma-delta (ΣΔ) ADC. This paper describes the process and reports the results of developing a fabrication process to robustly produce high-quality bump bonds to hybridize a back-illuminated detector with its ΣΔ ADC. The design utilizes aluminum pads on both the readout circuit and the photodiode array with interconnecting indium bumps between them. The development of the bump bonding process is discussed, including specific material choices, interim process structures, and final functionality. Results include measurements of bond integrity, cross-wafer uniformity of indium bumps, and effects of process parameters on the final product. Future plans for improving the bump bonding process are summarized.

  18. Interference Resilient Sigma Delta-Based Pulse Oximeter.

    PubMed

    Shokouhian, Mohsen; Morling, Richard; Kale, Izzet

    2016-06-01

    Ambient light and optical interference can severely affect the performance of pulse oximeters. The deployment of a robust modulation technique to drive the pulse oximeter LEDs can reduce these unwanted effects and increases the resilient of the pulse oximeter against artificial ambient light. The time division modulation technique used in conventional pulse oximeters can not remove the effect of modulated light coming from surrounding environment and this may cause huge measurement error in pulse oximeter readings. This paper presents a novel cross-coupled sigma delta modulator which ensures that measurement accuracy will be more robust in comparison with conventional fixed-frequency oximeter modulation technique especially in the presence of pulsed artificial ambient light. Moreover, this novel modulator gives an extra control over the pulse oximeter power consumption leading to improved power management. PMID:26742140

  19. On topological terms in the O(3) nonlinear sigma model

    NASA Astrophysics Data System (ADS)

    Tsurumaru, Toyohiro; Tsutsui, Izumi

    1999-08-01

    Topological terms in the O(3) nonlinear sigma model in (1+1) and (2+1) dimensions are re-examined based on the description of the SU(2)-valued field g. We first show that the topological soliton term in (1+1) dimensions arises from the unitary representations of the group characterizing the global structure of the symmetry inherent in the description, in a manner analogous to the appearance of the θ-term in Yang-Mills theory in (3+1) dimensions. We then present a detailed argument as to why the conventional Hopf term, which is the topological counterpart in (2+1) dimensions and has been widely used to realize fractional spin and statistics, is ill-defined unless the soliton charge vanishes. We show how this restriction can be lifted by means of a procedure proposed recently, and provide its physical interpretation as well.

  20. The sigma-1 receptor: roles in neuronal plasticity and disease

    PubMed Central

    Kourrich, Saïd; Su, Tsung-Ping; Fujimoto, Michiko; Bonci, Antonello

    2012-01-01

    Sigma-1 receptors (Sig-1Rs) have been implicated in many neurological and psychiatric conditions. The Sig-1R is an intracellular chaperone that resides specifically at the endoplasmic reticulum (ER)-mitochondrion interface referred to as the mitochondrion-associated ER membrane (MAM). Here, Sig-1Rs regulate ER-mitochondrion Ca2+ signaling. In this review, we discuss the current understanding of Sig-1R functions. Based on this, we suggest that the key cellular mechanism linking Sig-1Rs to neurological disorders involve the translocation of Sig-1Rs from the MAM to other parts of the cell, whereby Sig-1Rs bind and modulate the activities of various ion channels, receptors, or kinases. Thus, Sig-1Rs and their associated ligands may represent new avenues for treating some aspects of neurological and psychiatric diseases. PMID:23102998

  1. Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor.

    PubMed

    Omi, T; Tanimukai, H; Kanayama, D; Sakagami, Y; Tagami, S; Okochi, M; Morihara, T; Sato, M; Yanagida, K; Kitasyoji, A; Hara, H; Imaizumi, K; Maurice, T; Chevallier, N; Marchal, S; Takeda, M; Kudo, T

    2014-01-01

    We recently demonstrated that endoplasmic reticulum (ER) stress induces sigma-1 receptor (Sig-1R) expression through the PERK pathway, which is one of the cell's responses to ER stress. In addition, it has been demonstrated that induction of Sig-1R can repress cell death signaling. Fluvoxamine (Flv) is a selective serotonin reuptake inhibitor (SSRI) with a high affinity for Sig-1R. In the present study, we show that treatment of neuroblastoma cells with Flv induces Sig-1R expression by increasing ATF4 translation directly, through its own activation, without involvement of the PERK pathway. The Flv-mediated induction of Sig-1R prevents neuronal cell death resulting from ER stress. Moreover, Flv-induced ER stress resistance reduces the infarct area in mice after focal cerebral ischemia. Thus, Flv, which is used frequently in clinical practice, can alleviate ER stress. This suggests that Flv could be a feasible therapy for cerebral diseases caused by ER stress. PMID:25032855

  2. Teaching Lean Six Sigma within a Supply Chain Context: The Airplane Supply Chain Simulation

    ERIC Educational Resources Information Center

    Ellis, Scott C.; Goldsby, Thomas J.; Bailey, Ana M.; Oh, Jae-Young

    2014-01-01

    Lean six sigma is a management methodology that firms can employ to achieve substantial improvement in supply chain performance. However, few pedagogical exercises facilitate students' use of a comprehensive set of lean six sigma principles within a supply chain context. We describe the Airplane Supply Chain Simulation that helps students…

  3. 77 FR 1491 - Sigma Corporation; Analysis of Proposed Consent Order To Aid Public Comment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-10

    ... business justification. See In re Petroleum Products Antitrust Litig., 906 F.2d 432, 448 (9th Cir. 1990... Industries, Inc., 94 F.T.C. 6, 97-104 (1979). D. McWane and Sigma Conspired To Monopolize the Domestic DIPF... Sigma in this oligopolistic industry, Star seems much less culpable than the others. More...

  4. Facilitating Teamwork with Lean Six Sigma and Web-Based Technology

    ERIC Educational Resources Information Center

    Krause, Tim

    2009-01-01

    In this article, the author outlines a variety of ways of defining, making explicit, and supporting effective team-based projects through the basic tenets of Lean Six Sigma and the use of Web-based technologies. A combination of Lean Six Sigma and a handful of project management technologies not only help in fostering the communication central to…

  5. The Treatment of Six Sigma in Introductory Operations Management Textbooks: Clearing Up the Confusion

    ERIC Educational Resources Information Center

    Ravinder, Handanhal; Misra, Ram B.

    2016-01-01

    This paper critically examines the treatment of the statistical basis for Six Sigma and process capability in popular operations management textbooks. It discusses areas of confusion and suggest ways of treating the topic that make sense to instructors as well as students. Even though Six Sigma was introduced almost 30 years ago, misconceptions…

  6. Using Six Sigma for Performance Improvement in Business Curriculum: A Case Study

    ERIC Educational Resources Information Center

    Kukreja, Anil; Ricks, Joe M., Jr.; Meyer, Jean A.

    2009-01-01

    During the last few decades, a number of quality improvement methodologies have been used by organizations. This article provides a brief review of the quality improvement literature related to academia and a case study using Six Sigma methodology to analyze students' performance in a standardized examination. We found Six Sigma to be an effective…

  7. Activation of sigma-1 receptor chaperone in the treatment of neuropsychiatric diseases and its clinical implication.

    PubMed

    Hashimoto, Kenji

    2015-01-01

    Endoplasmic reticulum (ER) protein sigma-1 receptor represents unique chaperone activity in the central nervous system, and it exerts a potent influence on a number of neurotransmitter systems. Several lines of evidence suggest that activation of sigma-1 receptor plays a role in the pathophysiology of neuropsychiatric diseases, as well as in the mechanisms of some therapeutic drugs and neurosteroids. Preclinical studies showed that some selective serotonin reuptake inhibitors (SSRIs; fluvoxamine, fluoxetine, excitalopram), donepezil, and ifenprodil act as sigma-1 receptor agonists. Furthermore, sigma-1 receptor agonists could improve the N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP)-induced cognitive deficits in mice. A study using positron emission tomography have demonstrated that an oral administration of fluvoxamine or donepezil could bind to sigma-1 receptor in the healthy human brain, suggesting that sigma-1 receptor might be involved in the therapeutic mechanisms of these drugs. Moreover, case reports suggest that sigma-1 receptor agonists, including fluvoxamine, and ifenprodil, may be effective in the treatment of cognitive impairment in schizophrenia, delirium in elderly people, and flashbacks in post-traumatic stress disorder. In this review article, the author would like to discuss the clinical implication of sigma-1 receptor agonists, including endogenous neurosteroids, in the neuropsychiatric diseases. PMID:25704012

  8. Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site

    PubMed Central

    Xu, Jinbin; Zeng, Chenbo; Chu, Wenhua; Pan, Fenghui; Rothfuss, Justin M.; Zhang, Fanjie; Tu, Zhude; Zhou, Dong; Zeng, Dexing; Vangveravong, Suwanna; Johnston, Fabian; Spitzer, Dirk; Chang, Katherine C.; Hotchkiss, Richard S.; Hawkins, William G.; Wheeler, Kenneth T.; Mach, Robert H.

    2013-01-01

    The sigma-2 receptor, whose gene remains to be cloned, has been validated as a biomarker for tumor cell proliferation. Here we report the use of a novel photoaffinity probe, WC-21, to identify the sigma-2 receptor binding site. WC-21, a sigma-2 ligand containing both a photoactive moiety azide and a fluorescein isothiocyanate group, irreversibly labels sigma-2 receptors in rat liver; the membrane-bound protein was then identified as PGRMC1 (progesterone receptor membrane component-1). Immunocytochemistry reveals that both PGRMC1 and SW120, a fluorescent sigma-2 receptor ligand, colocalizes with molecular markers of the endoplasmic reticulum and mitochondria in HeLa cells. Overexpression and knockdown of the PGRMC1 protein results in an increase and a decrease in binding of a sigma-2 selective radioligand, respectively. The identification of the putative sigma-2 receptor binding site as PGRMC1 should stimulate the development of unique imaging agents and cancer therapeutics that target the sigma-2 receptor/PGRMC1 complex. PMID:21730960

  9. Improving Self Service the Six Sigma Way at Newcastle University Library

    ERIC Educational Resources Information Center

    Kumi, Susan; Morrow, John

    2006-01-01

    Purpose: To report on the collaborative project between Newcastle University Library and 3M which aimed to increase self-issue levels using six sigma methodology. Design/methodology/approach: The six-month long project is outlined and gives an insight into the process improvement methodology called six sigma. An explanation of why we ran the…

  10. Structured and Dynamic Disordered Domains Regulate the Activity of a Multifunctional Anti-σ Factor

    PubMed Central

    Herrou, Julien; Willett, Jonathan W.

    2015-01-01

    ABSTRACT The anti-σ factor NepR plays a central role in regulation of the general stress response (GSR) in alphaproteobacteria. This small protein has two known interaction partners: its cognate extracytoplasmic function (ECF) σ factor and the anti-anti-σ factor, PhyR. Stress-dependent phosphorylation of PhyR initiates a protein partner switch that promotes phospho-PhyR binding to NepR, which frees ECF σ to activate transcription of genes required for cell survival under adverse or fluctuating conditions. We have defined key functional roles for structured and intrinsically disordered domains of Caulobacter crescentus NepR in partner binding and activation of GSR transcription. We further demonstrate that NepR strongly stimulates the rate of PhyR phosphorylation in vitro and that this effect requires the structured and disordered domains of NepR. This result provides evidence for an additional layer of GSR regulation in which NepR directly influences activation of its binding partner, PhyR, as an anti-anti-σ factor. We conclude that structured and intrinsically disordered domains of NepR coordinately control multiple functions in the GSR signaling pathway, including core protein partner switch interactions and pathway activation by phosphorylation. PMID:26220965

  11. Extended Chiral ({sigma},{pi},{omega}) Mean-Field Model with Vacuum Fluctuation Corrections

    SciTech Connect

    Uechi, Schun T.; Uechi, Hiroshi

    2011-10-21

    Density-dependent relations among saturation properties of symmetric nuclear matter and properties of hadronic stars are discussed by applying the conserving chiral nonlinear ({sigma},{pi},{omega}) mean-field theory. The chiral nonlinear ({sigma},{pi},{omega}) mean-field theory is an extension of the conserving nonlinear (nonchiral){sigma}-{omega} mean-field theory, which is thermodynamically consistent, relativistic and Lorentz-covariant. In the extended chiral ({sigma},{pi},{omega}) mean-field model, all the masses of hadrons are produced by the spontaneous chiral symmetry breaking, which is different from conventional chiral partner models. By comparing both nonchiral and chiral mean-field approximations, the effects of the chiral symmetry breaking mechanism on the mass of {sigma}-meson, coefficients of nonlinear interactions and Fermi-liquid properties are investigated in nuclear matter and neutron stars.

  12. Sigma 1 protein of mammalian reoviruses extends from the surfaces of viral particles

    SciTech Connect

    Furlong, D.B.; Nibert, M.L.; Fields, B.N.

    1988-01-01

    Electron microscopy revealed structures consisting of long fibers topped with knobs extending from the surfaces of virions of mammalian reoviruses. The morphology of these structures was reminiscent of the fiber protein of adenovirus. Fibers were also seen extending from the reovirus top component and intermediate subviral particles but not from cores, suggesting that the fibers consist of either the ..mu..1C or sigma1 outer capsid protein. Amino acid sequence analysis predicts that the reovirus cell attachment protein sigma1 contains an extended fiber domain. When sigma1 protein was released from viral particles with mild heat and subsequently obtained in isolation, it was found to have a morphology identical to that of the fiber structures seen extending from the viral particles. The identification of an extended form of sigma1 has important implications for its function in cell attachment. Other evidence suggest that sigma1 protein may occur in virions in both an extended and an unextended state.

  13. Transition magnetic moment of {Lambda}{yields}{Sigma}{sup 0} in QCD sum rules

    SciTech Connect

    Lee, Frank X.; Wang Lai

    2011-05-01

    The {Lambda}{yields}{Sigma}{sup 0} transition magnetic moment is computed in the QCD sum rules approach. Three independent tensor structures are derived in the external-field method using generalized interpolating fields. They are analyzed together with the {Lambda} and {Sigma}{sup 0} mass sum rules using a Monte-Carlo-based analysis, with attention to operator product expansion convergence, ground-state dominance, and the role of the transitions in the intermediate states. Relations between sum rules for magnetic moments of {Lambda} and {Sigma}{sup 0} and sum rules for transition magnetic moment of {Lambda}{yields}{Sigma}{sup 0} are also examined. Our best prediction for the transition magnetic moment is {mu}{sub {Sigma}}{sup 0}{sub {Lambda}=}1.60{+-}0.07{mu}{sub N}. A comparison is made with other calculations in the literature.

  14. Direct observations of sigma phase growth and dissolution in 2205 duplex stainless steel

    SciTech Connect

    Palmer, T.A.; Elmer, J.W.; Babu, S.S.; Specht, E.D.

    2007-10-10

    The formation and growth of sigma ({sigma}) phase in a 2205 duplex stainless steel is monitored during an 850 C isothermal heat treatment using an in situ synchrotron x-ray diffraction technique. At this temperature, {sigma} phase is first observed within approximately 40 seconds of the start of the isothermal heat treatment and grows rapidly over the course of the 3600 second heat treatment to a volume fraction of approximately 13%. A simultaneous increase in the austenite ({gamma}) volume fraction and a decrease in the ferrite ({delta}) volume fraction are observed. The {sigma} phase formed at this temperature is rapidly dissolved within approximately 200 seconds when the temperature is increased to 1000 C. Accompanying this rapid dissolution of the {sigma} phase, the {delta} and {gamma} volume fractions both approach the balanced (50/50) level observed in the as-received material.

  15. Direct Observations of Sigma Phase Growth and Dissolution in 2205 Duplex Stainless Steel

    SciTech Connect

    Palmer, T; Elmer, J; Babu, S; Specht, E

    2005-06-14

    The formation and growth of sigma ({sigma}) phase in a 2205 duplex stainless steel is monitored during an 850 C isothermal heat treatment using an in situ synchrotron x-ray diffraction technique. At this temperature, {sigma} phase is first observed within approximately 40 seconds of the start of the isothermal heat treatment and grows rapidly over the course of the 3600 second heat treatment to a volume fraction of approximately 13%. A simultaneous increase in the austenite ({gamma}) volume fraction and a decrease in the ferrite ({delta}) volume fraction are observed. The {sigma} phase formed at this temperature is rapidly dissolved within approximately 200 seconds when the temperature is increased to 1000 C. Accompanying this rapid dissolution of the {sigma} phase, the {delta} and {gamma} volume fractions both approach the balanced (50/50) level observed in the as-received material.

  16. Isospin Decomposition of the Photoproduced Sigma pi System Near the Lambda(1405)

    SciTech Connect

    Schumacher, Reinhard A.; Moriya, Kei

    2013-09-01

    Recent experimental results for the reaction \\gamma + p \\to K^+ + \\Sigma + \\pi\\ from CLAS at Jefferson Lab are discussed. It was found that the mass distributions or "line shapes" of the three charge combinations \\Sigma^+ \\pi^-, \\Sigma^0 \\pi^0 and \\Sigma^- \\pi^+ differ significantly. Our results show that the \\Lambda(1405), as the I=0 constituent of the reaction, must be accompanied by an I > 0 component. We discuss phenomenological fits to the data to test the possible forms and magnitudes of these amplitudes. A two-amplitude I=0 fit of Breit-Wigner form to the \\Sigma^0\\pi^0 channel alone works quite well. The addition of a single I=1 amplitude works fairly well to model all the line shapes simultaneously.

  17. The low-lying 2-sigma-minus states of OH

    NASA Technical Reports Server (NTRS)

    Van Dishoeck, E. F.; Langhoff, S. R.; Dalgarno, A.

    1983-01-01

    The configuration-interaction method is used to determine the electronic wave functions of the two lowest 2-sigma-minus states of OH using four different atomic orbital basis sets. Potential energy curves, transition moments, oscillator strengths, and photodissociation cross sections are obtained. Electronic transition dipole moments connecting the excited 1 2-sigma-minus and 2(D)2-sigma-minus states with each other and with the ground chi-2-pi state are presented as functions of internuclear distance. The theoretical absorption oscillator strengths for the D-2-sigma-minus(v prime = 0) from chi-2-pi(v double prime = 0) transition are in good agreement with the empirical value derived from astronomical measurement. The photodissociation cross sections for absorption from the v prime = 0, 1, and 2 levels of the ground state into the continuum of the 1 2-sigma-minus state are calculated, and the interstellar and cometary photodissociation rates are derived.

  18. Hyperfine structure and Zeeman tuning of the A {sup 2}PI-X {sup 2}SIGMA{sup +}(0,0) band system of the odd isotopologue of strontium monofluoride {sup 87}SrF

    SciTech Connect

    Le, Anh T.; Wang Hailing; Steimle, Timothy C.

    2009-12-15

    The low-rotational lines of the A {sup 2}PI-X {sup 2}SIGMA{sup +}(0,0) band system of the odd isotopologue of strontium monofluoride, {sup 87}SrF, were recorded and analyzed. The {sup 87}Sr(I=9/2) magnetic hyperfine interaction is significant only in the |OMEGA|=1/2 spin-orbit component of the A {sup 2}PI state. Optical transitions appropriate for monitoring ultracold samples of {sup 87}SrF are identified. The determined fine-structure parameters were used to predict the anisotropic magnetic g factor, g{sub l}, for the X {sup 2}SIGMA{sup +}(v=0) state. The g factors were used to predict the magnetic tuning of the N=0 (+parity) and N=1 (-parity) levels of the X {sup 2}SIGMA{sup +}(v=0) state. A comparison to spectroscopic parameters for the {sup 88}SrF isotopologue is given.

  19. The Dose Rate Conversion Factors for Nuclear Fallout

    SciTech Connect

    Spriggs, G D

    2009-02-13

    In a previous paper, the composite exposure rate conversion factor (ECF) for nuclear fallout was calculated using a simple theoretical photon-transport model. The theoretical model was used to fill in the gaps in the FGR-12 table generated by ORNL. The FGR-12 table contains the individual conversion factors for approximate 1000 radionuclides. However, in order to calculate the exposure rate during the first 30 minutes following a nuclear detonation, the conversion factors for approximately 2000 radionuclides are needed. From a human-effects standpoint, it is also necessary to have the dose rate conversion factors (DCFs) for all 2000 radionuclides. The DCFs are used to predict the whole-body dose rates that would occur if a human were standing in a radiation field of known exposure rate. As calculated by ORNL, the whole-body dose rate (rem/hr) is approximately 70% of the exposure rate (R/hr) at one meter above the surface. Hence, the individual DCFs could be estimated by multiplying the individual ECFs by 0.7. Although this is a handy rule-of-thumb, a more consistent (and perhaps, more accurate) method of estimating the individual DCFs for the missing radionuclides in the FGR-12 table is to use the linear relationship between DCF and total gamma energy released per decay. This relationship is shown in Figure 1. The DCFs for individual organs in the body can also be estimated from the estimated whole-body DCF. Using the DCFs given FGR-12, the ratio of the organ-specific DCFs to the whole-body DCF were plotted as a function of the whole-body DCF. From these plots, the asymptotic ratios were obtained (see Table 1). Using these asymptotic ratios, the organ-specific DCFs can be estimated using the estimated whole-body DCF for each of the missing radionuclides in the FGR-12 table. Although this procedure for estimating the organ-specific DCFs may over-estimate the value for some low gamma-energy emitters, having a finite value for the organ-specific DCFs in the table is

  20. Magnetic detection of sigma phase in duplex stainless steel UNS S31803

    NASA Astrophysics Data System (ADS)

    Tavares, S. S. M.; Pardal, J. M.; Guerreiro, J. L.; Gomes, A. M.; da Silva, M. R.

    2010-09-01

    Duplex stainless steels are high strength and corrosion resistant steels extensively used in the chemical and petrochemical industry. The best mechanical properties and corrosion resistance are obtained with a microstructure composed by equal parts of ferrite and austenite and free from tertiary phases. Sigma phase is one of these deleterious tertiary phases. In the present work different amounts of sigma phase were precipitated by heat treatments in a UNS S31803 stainless steel. Some specimens were cold rolled before sigma phase precipitation in order to evaluate the effect of deformation on the magnetic measurements. The amount of sigma phase was precisely determined by microscopy and image analysis for each heat treatment condition. The effects of sigma phase on the steel properties were investigated, confirming the detrimental effects of very small percentages on corrosion resistance and toughness. Two magnetic methods were used to detect sigma phase: magnetization saturation measurements in a Vibrating Sample Magnetometer and ferritoscope testing. Both methods were found to be sensitive to small percentages of sigma phase in the microstructure.

  1. Sigma: Strain-level inference of genomes from metagenomic analysis for biosurveillance

    DOE PAGESBeta

    Ahn, Tae-Hyuk; Chai, Juanjuan; Pan, Chongle

    2014-09-29

    Motivation: Metagenomic sequencing of clinical samples provides a promising technique for direct pathogen detection and characterization in biosurveillance. Taxonomic analysis at the strain level can be used to resolve serotypes of a pathogen in biosurveillance. Sigma was developed for strain-level identification and quantification of pathogens using their reference genomes based on metagenomic analysis. Results: Sigma provides not only accurate strain-level inferences, but also three unique capabilities: (i) Sigma quantifies the statistical uncertainty of its inferences, which includes hypothesis testing of identified genomes and confidence interval estimation of their relative abundances; (ii) Sigma enables strain variant calling by assigning metagenomic readsmore » to their most likely reference genomes; and (iii) Sigma supports parallel computing for fast analysis of large datasets. In conclusion, the algorithm performance was evaluated using simulated mock communities and fecal samples with spike-in pathogen strains. Availability and Implementation: Sigma was implemented in C++ with source codes and binaries freely available at http://sigma.omicsbio.org.« less

  2. Topography of Slow Sigma Power during Sleep is Associated with Processing Speed in Preschool Children

    PubMed Central

    Doucette, Margaret R.; Kurth, Salome; Chevalier, Nicolas; Munakata, Yuko; LeBourgeois, Monique K.

    2015-01-01

    Cognitive development is influenced by maturational changes in processing speed, a construct reflecting the rapidity of executing cognitive operations. Although cognitive ability and processing speed are linked to spindles and sigma power in the sleep electroencephalogram (EEG), little is known about such associations in early childhood, a time of major neuronal refinement. We calculated EEG power for slow (10–13 Hz) and fast (13.25–17 Hz) sigma power from all-night high-density electroencephalography (EEG) in a cross-sectional sample of healthy preschool children (n = 10, 4.3 ± 1.0 years). Processing speed was assessed as simple reaction time. On average, reaction time was 1409 ± 251 ms; slow sigma power was 4.0 ± 1.5 μV2; and fast sigma power was 0.9 ± 0.2 μV2. Both slow and fast sigma power predominated over central areas. Only slow sigma power was correlated with processing speed in a large parietal electrode cluster (p < 0.05, r ranging from −0.6 to −0.8), such that greater power predicted faster reaction time. Our findings indicate regional correlates between sigma power and processing speed that are specific to early childhood and provide novel insights into the neurobiological features of the EEG that may underlie developing cognitive abilities. PMID:26556377

  3. Kinetic Study to Predict Sigma Phase Formation in Duplex Stainless Steels

    NASA Astrophysics Data System (ADS)

    dos Santos, Daniella Caluscio; Magnabosco, Rodrigo

    2016-04-01

    This work presents an improved kinetic study of sigma phase formation during isothermal aging between 973 K and 1223 K (700 °C and 950 °C), based on Kolmogorov-Johnson-Mehl-Avrami (K-J-M-A) model, established from volume fraction of sigma phase determined in backscattered electron images over polished surfaces of aged samples. The kinetic study shows a change in the main mechanism of sigma formation between 973 K and 1173 K (700 °C and 900 °C), from a nucleation-governed stage to a diffusion-controlled growth-coarsening stage, confirmed by a double inclination in K-J-M-A plots and microstructural observations. A single inclination in K-J-M-A plots was observed for the 1223 K (950 °C) aging temperature, showing that kinetic behavior in this temperature is only related to diffusion-controlled growth of sigma phase. The estimated activation energies for the nucleation of sigma phase are close to the molybdenum diffusion in ferrite, probably the controlling mechanism of sigma phase nucleation. The proposed time-temperature-transformation (TTT) diagram shows a "double c curve" configuration, probably associated to the presence of chi-phase formed between 973 K and 1073 K (700 °C and 800 °C), which acts as heterogeneous nuclei for sigma phase formation in low aging temperatures.

  4. Dominant lethal phenotype of a mutation in the -35 recognition region of Escherichia coli sigma 70.

    PubMed Central

    Keener, J; Nomura, M

    1993-01-01

    A dominant lethal mutation in the Escherichia coli rpoD gene, which encodes sigma 70, the promoter recognition subunit of RNA polymerase, was isolated after random mutagenesis. The lethal gene was maintained under control of the lac repressor on a low copy plasmid. An amount of lethal sigma 70 that was nearly equimolar with the chromosomally encoded sigma 70 was sufficient to cause cessation of growth. RNA synthesis per unit cell mass was unaffected, but protein synthesis was inhibited by the mutant sigma 70. The amino acid change (Glu-585 to Gln) was in a region of sigma 70 thought to bind the -35 hexamer of the promoter, and the mutant sigma 70 caused increased expression from promoters with nonconsensus bases in the third position of the -35 hexamer. A null mutation of the fis gene could partially suppress the mutant phenotype. These properties are consistent with those expected of a sigma 70 insensitive to growth rate control of rRNA and tRNA promoters. Images Fig. 2 PMID:7680477

  5. Sox transcription in sarcosine utilization is controlled by Sigma(54) and SoxR in Bacillus thuringiensis HD73.

    PubMed

    Peng, Qi; Liu, Chunxia; Wang, Bo; Yang, Min; Wu, Jianbo; Zhang, Jie; Song, Fuping

    2016-01-01

    Sarcosine oxidase catalyzes the oxidative demethylation of sarcosine to yield glycine, formaldehyde, and hydrogen peroxide. In this study, we analyzed the transcription and regulation of the sox locus, including the sarcosine oxidase-encoding genes in Bacillus thuringiensis (Bt). RT-PCR analysis revealed that the sox locus forms two opposing transcriptional units: soxB (soxB/E/F/G/H/I) and soxR (soxR/C/D/A). The typical -12/-24 consensus sequence was located 15 bp and 12 bp from the transcriptional start site (TSS) of soxB and soxC, respectively. Promoter-lacZ fusion assays showed that the soxB promoter is controlled by the Sigma(54) factor and is activated by the Sigma(54)-dependent transcriptional regulator SoxR. SoxR also inhibits its own expression. Expression from the PsoxCR promoter, which is responsible for the transcription of soxC, soxD, and soxA, is Sigma(54)-dependent and requires SoxR. An 11-bp inverted repeat sequence was identified as SoxR binding site upstream of the soxB TSS. Purified SoxR specifically bound a DNA fragment containing this region. Mutation or deletion of this sequence abolished the transcriptional activities of soxB and soxC. Thus, SoxR binds to the same sequence to activate the transcription of soxB and soxC. Sarcosine utilization was abolished in soxB and soxR mutants, suggesting that the sox locus is essential for sarcosine utilization. PMID:27404799

  6. Sox transcription in sarcosine utilization is controlled by Sigma54 and SoxR in Bacillus thuringiensis HD73

    PubMed Central

    Peng, Qi; Liu, Chunxia; Wang, Bo; Yang, Min; Wu, Jianbo; Zhang, Jie; Song, Fuping

    2016-01-01

    Sarcosine oxidase catalyzes the oxidative demethylation of sarcosine to yield glycine, formaldehyde, and hydrogen peroxide. In this study, we analyzed the transcription and regulation of the sox locus, including the sarcosine oxidase-encoding genes in Bacillus thuringiensis (Bt). RT-PCR analysis revealed that the sox locus forms two opposing transcriptional units: soxB (soxB/E/F/G/H/I) and soxR (soxR/C/D/A). The typical −12/−24 consensus sequence was located 15 bp and 12 bp from the transcriptional start site (TSS) of soxB and soxC, respectively. Promoter-lacZ fusion assays showed that the soxB promoter is controlled by the Sigma54 factor and is activated by the Sigma54-dependent transcriptional regulator SoxR. SoxR also inhibits its own expression. Expression from the PsoxCR promoter, which is responsible for the transcription of soxC, soxD, and soxA, is Sigma54-dependent and requires SoxR. An 11-bp inverted repeat sequence was identified as SoxR binding site upstream of the soxB TSS. Purified SoxR specifically bound a DNA fragment containing this region. Mutation or deletion of this sequence abolished the transcriptional activities of soxB and soxC. Thus, SoxR binds to the same sequence to activate the transcription of soxB and soxC. Sarcosine utilization was abolished in soxB and soxR mutants, suggesting that the sox locus is essential for sarcosine utilization. PMID:27404799

  7. Stationary-phase-inducible "gearbox" promoters: differential effects of katF mutations and role of sigma 70.

    PubMed

    Bohannon, D E; Connell, N; Keener, J; Tormo, A; Espinosa-Urgel, M; Zambrano, M M; Kolter, R

    1991-07-01

    Many of the changes in gene expression observed when Escherichia coli cells enter stationary phase are regulated at the level of transcription initiation. A group of stationary-phase-inducible promoters, known as "gearbox" promoter, display a characteristic sequence in the -10 region which differs greatly from the consensus sequence for sigma 70-dependent promoters. Here we describe our studies on the gearbox promoters bolAp1 and mcbAp, responsible for the temporally regulated transcription of bolA and the genes involved in the synthesis of the peptide antibiotic microcin B17, respectively. Deletion analysis of mcbAp demonstrated that the stationary-phase-inducible properties of this promoter are found in a DNA fragment extending from -54 to +11 bp, surrounding the transcriptional start site, and are separable from DNA sequences responsible for the OmpR-dependent stimulation of transcription of mcbAp. In vitro transcription studies indicate that the RNA polymerase holoenzyme involved in the transcription of mcbAp contains sigma 70. In this and an accompanying paper (R. Lange and R. Hengge-Aronis, J. Bacteriol. 173: 4474-4481, 1991), experiments are described which show that the product of katF, a global regulator of stationary-phase gene expression and a putative sigma factor, is required for the expression of bolAp1 fused to the reporter gene lacZ. In contrast, mcbAp appears to be negatively regulated by katF. We discuss the implications of these results for postexponential gene expression and the role of gearbox sequences in the regulation of promoter activity. PMID:1906064

  8. First Observation of the Cabibbo-suppressed Decays Xi+(c) ---> Sigma+ pi- pi+ and Xi+(c) ---> Sigma- pi+ pi+ and Measurement of their Branching Ratios

    SciTech Connect

    Vazquez-Jauregui, E.; Engelfried, J.; Akgun, U.; Alkhazov, Georgiy; Amaro-Reyes, J.; Atamantchouk, A.G.; Ayan, Ahmet Sedat; Balatz, M.Y.; Blanco-Covarrubias, A.; Bondar, N.F.; Cooper, Peter S.; /Fermilab /Michigan U., Flint

    2008-04-01

    The authors report the first observation of two Cabibbo-suppressed decay modes, {Xi}{sub c}{sup +} {yields} {Sigma}{sup +}{pi}{sup -}{pi}{sup +} and {Xi}{sub c}{sup +} {yields} {Sigma}{sup -} {pi}{sup +}{pi}{sup +}. They observe 56 {+-} 13 over a background of 21, and 23 {+-} 7 over a background of 12 events, respectively, for the signals. The data were accumulated using the SELEX spectrometer during the 1996-1997 fixed target run at Fermilab, chiefly from a 600 GeV/c {Sigma}{sup -} beam. The branching ratios of the decays relative to the Cabibbo-favored {Xi}{sub c}{sup +} {yields} {Xi}{sup -}{pi}{sup +}{pi}{sup +} are measured to be B({Xi}{sub c}{sup +} {yields} {Sigma}{sup +}{pi}{sup -}{pi}{sup +})/B({xi}{sub c}{sup +} {yields} {Xi}{sup -} {pi}{sup +}{pi}{sup +}) = 0.50 {+-} 0.20, and B({Xi}{sub c}{sup +} {yields} {Sigma}{sup -}{pi}{sup +}{pi}{sup +})/B({Xi}{sub c}{sup +} {yields} {Xi}{sup -}{pi}{sup +}{pi}{sup +}) = 0.23 {+-} 0.11, respectively. They also report branching ratios for the same decay modes of the {Lambda}{sub c}{sup +} relative to {Lambda}{sub c}{sup +} {yields} pK{sup -}{pi}{sup +}.

  9. Maturational Patterns of Sigma Frequency Power Across Childhood and Adolescence: A Longitudinal Study

    PubMed Central

    Campbell, Ian G.; Feinberg, Irwin

    2016-01-01

    Study Objectives: To further evaluate adolescent brain maturation by determining the longitudinal trajectories of nonrapid eye movement (NREM) sigma (11–15 Hz) power across childhood-adolescence. Methods: The maturational trend for sigma (11–15 Hz) power was evaluated in an accelerated longitudinal study of three overlapping age cohorts (n = 92) covering ages 6 to 18 y. Semiannually, sleep electroencephalography (EEG) was recorded from participants sleeping at home in their normal sleep environment while keeping their current school night schedules. Results: Sigma frequencies became faster with age. The frequency of the 11–15 Hz spectral peak increased linearly. Sigma frequency power (SFP) declined with age, but its trajectory was complex (cubic). Power in a group of low sigma subfrequencies declined with age. Power in a group of high sigma frequencies increased with age. Power in subfrequencies within 11–15 Hz also showed different trends across the night, with lower frequencies increasing across NREM periods and higher frequencies decreasing across NREM periods. The upper and lower boundaries for the sigma frequencies that changed across NREMPs shifted upward with age. Conclusions: We hypothesize that these maturational brain changes result from synaptic elimination which decreases sleep depth and streamlines circuits. SFP displays a maturational trajectory different from both delta and theta power. Theories on the function of sigma must be reconciled with its maturational trajectory. These findings further demonstrate the value of sleep EEG for studying noninvasively the complex developmental brain changes of adolescence. Citation: Campbell IG, Feinberg I. Maturational patterns of sigma frequency power across childhood and adolescence: a longitudinal study. SLEEP 2016;39(1):193–201. PMID:26285004

  10. Infrared CO line for the X 1 Sigma(+) state

    NASA Technical Reports Server (NTRS)

    Goorvitch, D.

    1994-01-01

    A complete line list with improved accuracy for all the rotation-vibration transitions of the fundamental, first, and second overtone bands up to v = 20 and J = 149 of the gradual state X 1 Sigma(+) of the seven CO isotopes -- (12)C(16)O, (13)C(16)O, (12)C(17)O, (12)C(18)O, (13)C(18)O, (14)C(16)O, and (13)c(17)O -- is made available to the astronomical community. A line list of the pure rotational transitions up to v = 5 and J = 60 is also made available for these seven isotopes. This line list contains the transition frequency, the lower state energy, the Einstein A-value, the g f-value, the transition strength at 3000 K or 1000 K for the pure rotational transitions, the expectation value of the effective dipole moment operator, and the quantum numbers of each transition. Individual partition functions are reported in the temperature range of 500 to 10,000 K. This line list is available as four text files from the author using an anonymous file transfer protocol (ftp) transfer and in computer-readable form in the AAS CD-ROM Series, Vol. 3.

  11. Supersymmetric sigma model of disordered, isotropic, elastic media

    NASA Astrophysics Data System (ADS)

    Photiadis, Douglas

    The supersymmetry method proposed by Efetov in 1983 has been enormously successful at describing a broad range of phenomena involving disorder, providing a framework for understanding and going beyond the successes of random matrix theory and allowing a calculation of the slowing of diffusion as the Anderson transition is approached. The original model described the propagation of a scalar wave in a disordered medium, and subsequent work extended these ideas to classical waves, optical or elastic, with the approximation that the wave propagation can be similarly described by a scalar theory. Such a theory cannot however account correctly for scattering between different polarizations. A direct attempt to derive a supersymmetric model describing elastic waves results in a non-renormalizable field theory, and poses substantial difficulties. We have obtained a supersymmetric sigma model by considering the dual model which describes a generalized superstress field. The model enables one to fully account for the different wave types and polarizations in the medium. We will present our recent results in this area, including model predictions for the obtained diffusion constants, and the effects of renormalization to first order. This research was funded by the Office of Naval Research.

  12. Sigma-2 Receptor as Potential Indicator of Stem Cell Differentiation

    PubMed Central

    Haller, Jodi L.; Panyutin, Irina; Chaudhry, Aneeka; Zeng, Chenbo; Mach, Robert H.; Frank, Joseph A.

    2011-01-01

    Purpose The sigma-2 (σ2) receptor is a potential biomarker of proliferative status of solid tumors. Specific synthetic probes using N-substituted-9-azabicyclo[3.3.1]nonan-3α-yl carbamate analogs have been designed and implemented for experimental cancer diagnosis and therapy. Procedures We employed the fluorescently-labeled σ2 receptor probe, SW120, to evaluate σ2 receptor expression in human stem cells (SC), including: bone marrow stromal (BMSC), neural progenitor (NPC), amniotic fluid (AFSC), hematopoetic (HSC) and embryonic stem cells (ESC). We concurrently evaluated the intensity of SW120 and 5-ethynyl-2′-deoxyuridine (EdU) relative to passage number and multipotency. Results We substantiated significantly higher σ2 receptor density among proliferating SC relative to lineage-restricted cell types. Additionally, cellular internalization of the σ2 receptor in SC was consistent with receptor-mediated endocytosis and confocal microscopy indicated SW120 specific co-localization with a fluorescent marker of lysosomes in all SC imaged. Conclusion These results suggest that σ2 receptors may serve to monitor stem cell differentiation in future experimental studies. PMID:21614680

  13. A High Performance Delta-Sigma Modulator for Neurosensing.

    PubMed

    Xu, Jian; Zhao, Menglian; Wu, Xiaobo; Islam, Md Kafiul; Yang, Zhi

    2015-01-01

    Recorded neural data are frequently corrupted by large amplitude artifacts that are triggered by a variety of sources, such as subject movements, organ motions, electromagnetic interferences and discharges at the electrode surface. To prevent the system from saturating and the electronics from malfunctioning due to these large artifacts, a wide dynamic range for data acquisition is demanded, which is quite challenging to achieve and would require excessive circuit area and power for implementation. In this paper, we present a high performance Delta-Sigma modulator along with several design techniques and enabling blocks to reduce circuit area and power. The modulator was fabricated in a 0.18-µm CMOS process. Powered by a 1.0-V supply, the chip can achieve an 85-dB peak signal-to-noise-and-distortion ratio (SNDR) and an 87-dB dynamic range when integrated over a 10-kHz bandwidth. The total power consumption of the modulator is 13 µW, which corresponds to a figure-of-merit (FOM) of 45 fJ/conversion step. These competitive circuit specifications make this design a good candidate for building high precision neurosensors. PMID:26262623

  14. An ABET assessment model using Six Sigma methodology

    NASA Astrophysics Data System (ADS)

    Lalovic, Mira

    Technical fields are changing so rapidly that even the core of an engineering education must be constantly reevaluated. Graduates of today give more dedication and, almost certainly, more importance to continued learning than to mastery of specific technical concepts. Continued learning shapes a high-quality education, which is what an engineering college must offer its students. The question is how to guarantee the quality of education. In addition, the Accreditation Board of Engineering and Technology is asking that universities commit to continuous and comprehensive education, assuming quality of the educational process. The research is focused on developing a generic assessment model for a college of engineering as an annual cycle that consists of a systematic assessment of every course in the program, followed by an assessment of the program and of the college as a whole using Six Sigma methodology. This unique approach to assessment in education will provide a college of engineering with valuable information regarding many important curriculum decisions in every accreditation cycle. The Industrial and Manufacturing Engineering (IME) Program in the College of Engineering at the University of Cincinnati will be used as a case example for a preliminary test of the generic model.

  15. A High Performance Delta-Sigma Modulator for Neurosensing

    PubMed Central

    Xu, Jian; Zhao, Menglian; Wu, Xiaobo; Islam, Md. Kafiul; Yang, Zhi

    2015-01-01

    Recorded neural data are frequently corrupted by large amplitude artifacts that are triggered by a variety of sources, such as subject movements, organ motions, electromagnetic interferences and discharges at the electrode surface. To prevent the system from saturating and the electronics from malfunctioning due to these large artifacts, a wide dynamic range for data acquisition is demanded, which is quite challenging to achieve and would require excessive circuit area and power for implementation. In this paper, we present a high performance Delta-Sigma modulator along with several design techniques and enabling blocks to reduce circuit area and power. The modulator was fabricated in a 0.18-μm CMOS process. Powered by a 1.0-V supply, the chip can achieve an 85-dB peak signal-to-noise-and-distortion ratio (SNDR) and an 87-dB dynamic range when integrated over a 10-kHz bandwidth. The total power consumption of the modulator is 13 μW, which corresponds to a figure-of-merit (FOM) of 45 fJ/conversion step. These competitive circuit specifications make this design a good candidate for building high precision neurosensors. PMID:26262623

  16. Amplitude relations in non-linear sigma model

    NASA Astrophysics Data System (ADS)

    Chen, Gang; Du, Yi-Jian

    2014-01-01

    In this paper, we investigate tree-level scattering amplitude relations in U( N) non-linear sigma model. We use Cayley parametrization. As was shown in the recent works [23,24], both on-shell amplitudes and off-shell currents with odd points have to vanish under Cayley parametrization. We prove the off-shell U(1) identity and fundamental BCJ relation for even-point currents. By taking the on-shell limits of the off-shell relations, we show that the color-ordered tree amplitudes with even points satisfy U(1)-decoupling identity and fundamental BCJ relation, which have the same formations within Yang-Mills theory. We further state that all the on-shell general KK, BCJ relations as well as the minimal-basis expansion are also satisfied by color-ordered tree amplitudes. As a consequence of the relations among color-ordered amplitudes, the total 2 m-point tree amplitudes satisfy DDM form of color decomposition as well as KLT relation.

  17. A Visual-Spectroscopic Orbit for the Binary Sigma 248

    NASA Astrophysics Data System (ADS)

    Torres, Guillermo

    1995-06-01

    Spectroscopic studies of visual binaries with angular separations less than about 1" have so far had great difficulty in providing the individual radial velocities for the components, because of the small velocity differences that are typical in these systems. The recent introduction of TODCOR, a two-dimensional cross-correlation technique (Zucker and Mazeh 1994), promises to change the situation, bridging the gap between the wider pairs resolvable at the telescope, and the classical double-lined spectroscopic binaries, with large velocity amplitudes. We present the first example of an application of TODCOR to such a case: the study of the close visual pair Sigma 248. We report our high-resolution low signal-to-noise spectroscopic observations of the system over the past seven years, which happen to cover the periastron passage. Using TODCOR, we are able to disentangle the light from the two stars in our composite spectra and obtain radial velocities for both components despite the small velocity difference. By combining our velocities with all available astrometric observations of the pair we derive for the first time a visual-spectroscopic orbital solution, with a period of about 310 years. We obtain also the orbital parallax of the system, corresponding to a distance of 60 parsecs, as well as the individual masses, which are consistent with early K-type dwarfs. (SECTION: Stars)

  18. Optimizing The DSSC Fabrication Process Using Lean Six Sigma

    NASA Astrophysics Data System (ADS)

    Fauss, Brian

    Alternative energy technologies must become more cost effective to achieve grid parity with fossil fuels. Dye sensitized solar cells (DSSCs) are an innovative third generation photovoltaic technology, which is demonstrating tremendous potential to become a revolutionary technology due to recent breakthroughs in cost of fabrication. The study here focused on quality improvement measures undertaken to improve fabrication of DSSCs and enhance process efficiency and effectiveness. Several quality improvement methods were implemented to optimize the seven step individual DSSC fabrication processes. Lean Manufacturing's 5S method successfully increased efficiency in all of the processes. Six Sigma's DMAIC methodology was used to identify and eliminate each of the root causes of defects in the critical titanium dioxide deposition process. These optimizations resulted with the following significant improvements in the production process: 1. fabrication time of the DSSCs was reduced by 54 %; 2. fabrication procedures were improved to the extent that all critical defects in the process were eliminated; 3. the quantity of functioning DSSCs fabricated was increased from 17 % to 90 %.

  19. Modulation of serotonergic neurotransmission by short- and long-term treatments with sigma ligands.

    PubMed

    Bermack, J E; Debonnel, G

    2001-10-01

    1. Sigma receptors were first described in 1976 as opiate receptors but were later determined to be a distinct class of receptors with two subtypes, sigma(1) and sigma(2). Although the endogenous ligand is yet to be elucidated, the sigma(1) receptor has recently been cloned. 2. Behavioural models used to test potential antidepressants have shown sigma ligands to produce antidepressant effects but their mechanism of action is unknown. 3. The goal of the present study was to assess the effects of various sigma(1) ligands on the firing activity of serotonin (5-HT) neurons of the dorsal raphe nucleus (DRN) using extracellular in vivo recordings in anaesthetized rats. 4. The sigma(1) ligands (+)-pentazocine and 4-(N-benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP) (2 mg kg(-1) day(-1)) increased markedly 5-HT firing activity after 2 days of treatment and maintained the same increased firing rate after long-term (21 days) treatments. Furthermore, the increased firing rate produced by 2 and 21 day treatments with (+)-pentazocine was prevented by the co-administration of N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)-thylamine (NE-100) (10 mg kg(-1) day(-1)) a selective sigma(1) antagonist, confirming the sigma(1) receptor's modulation of these effects. In contrast, the sigma(1) ligands (+)-N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1-1-ethyl-but-3-en-1-ylamine hydrochloride (JO-1784) and 2-(4-morpholinoethyl 1-phenyl-cyclohexane-1-carboxylate hydrochloride (PRE-084) had no effect. 5. Following a 21-day treatment with (+)-pentazocine there was a marked reduction in the number of neurons found per track. This decrease was not seen after chronic treatment with 4-IBP and may represent a depolarization block. 6. These results suggest a modulation of serotonergic neurotransmission by some sigma receptors and provide a potential mechanism for the 'antidepressant effects' reported and provide evidence toward sigma(1) ligands as potential antidepressants with a rapid onset of

  20. When the endogenous hallucinogenic trace amine N,N-dimethyltryptamine meets the sigma-1 receptor.

    PubMed

    Su, Tsung-Ping; Hayashi, Teruo; Vaupel, D Bruce

    2009-01-01

    N,N-dimethyltryptamine (DMT) is a hallucinogen found endogenously in human brain that is commonly recognized to target the 5-hydroxytryptamine 2A receptor or the trace amine-associated receptor to exert its psychedelic effect. DMT has been recently shown to bind sigma-1 receptors, which are ligand-regulated molecular chaperones whose function includes inhibiting various voltage-sensitive ion channels. Thus, it is possible that the psychedelic action of DMT might be mediated in part through sigma-1 receptors. Here, we present a hypothetical signaling scheme that might be triggered by the binding of DMT to sigma-1 receptors. PMID:19278957

  1. When the Endogenous Hallucinogenic Trace Amine N,N-Dimethyltryptamine Meets the Sigma-1 Receptor

    PubMed Central

    Su, Tsung-Ping; Hayashi, Teruo; Vaupel, D. Bruce

    2011-01-01

    N,N-dimethyltryptamine (DMT) is a hallucinogen found endogenously in human brain that is commonly recognized to target the 5-hydroxytryptamine 2A receptor or the trace amine–associated receptor to exert its psychedelic effect. DMT has been recently shown to bind sigma-1 receptors, which are ligand-regulated molecular chaperones whose function includes inhibiting various voltage-sensitive ion channels. Thus, it is possible that the psychedelic action of DMT might be mediated in part through sigma-1 receptors. Here, we present a hypothetical signaling scheme that might be triggered by the binding of DMT to sigma-1 receptors. PMID:19278957

  2. Medium modification of nucleon properties in a Walecka - Linear Sigma Model description

    SciTech Connect

    Alberto, P.; Fiolhais, M.; Bracco, M.E.; Chiapparini, M.

    2004-12-02

    Medium modification of nucleon properties are studied in the framework of the Linear Sigma Model (LSM). The nucleon is described as a chiral soliton with 3-quarks bounded due to their interactions with sigma and pion fields. Medium effects are introduced through the coupling of the quarks to sigma and omega fields, the strengths of which are determined self-consistently in a Walecka-like model, whose fermionic nucleon mass is calculated in the framework of the LSM. The nucleon properties are presented as functions of the nuclear density.

  3. The A6Sigma+ - X6Sigma+ Transition of CrH, Einstein Coefficients and an Improved Description of the A State

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Ram, R. S.; Bernath, Peter F.; Parsons, C. G.; Galehouse, D.; Arnold, James O. (Technical Monitor)

    2001-01-01

    The spectrum of CrH has been reinvestigated in the 9000-15000/cm region using the Fourier transform spectrometer of the National Solar Observatory. The 1-0 and 1-1 bands of the A6Sigma+ - X6Sigma+ transition have been measured and improved spectroscopic constants have been determined. A value for the 2-0 band origin has been obtained from the band head using estimated spectroscopic constants. These data provide a set of much improved equilibrium vibrational and rotational constants for the A6Sigma+ state. An accurate description of the A-X transition has been obtained using a multi-reference configuration interaction approach. The inclusion of both scalar relativity and Cr 3s3p correlation are required to obtain a good description of both states. The ab initio computed Einstein coefficients and radiative lifetimes are reported.

  4. Product branching ratios of the NH({sup 3}{Sigma}{sup -}) + NO and NH({sup 3}{Sigma}{sup -}) + NO{sub 2} reactions

    SciTech Connect

    Quandt, R.W.; Hershberger, J.F.

    1995-11-16

    The title reactions were studied at 298 K using time-resolved infrared diode laser spectroscopy. For the NH ({sup 3}{Sigma}{sup -}) + NO reaction, N{sub 2}O + H were found to be the primary products, with a branching ratio of 0.77 {+-} 0.08, in good agreement with other recent measurements. For the NH ({sup 3} {Sigma}{sup -}) + NO{sub 2} reaction, the measured branching ratio was 0.41 {+-} 0.15 into the N{sub 2}O + OH channel and 0.59 {+-} 0.15 into the NO + HNO channel. 45 refs., 5 figs., 3 tabs.

  5. OBSERVATIONS RELATED TO THE USE OF THE SIGMA COORDINATE TRANSFORMATION FOR ESTUARIES AND COASTAL MODELING STUDIES

    EPA Science Inventory

    One of the common techniques used in application of time-dependent, three-dimensional models addressing estuarine and coastal environmental problems is the sigma coordinate transformation. his transformation has proven useful in applications with highly irregular bottom topograph...

  6. 78 FR 5499 - Manufacturer of Controlled Substances, Notice of Registration; Sigma Aldrich Research...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-25

    ... October 2, 2012, 77 FR 60145, Sigma Aldrich Research Biochemicals, Inc., 1-3 Strathmore Road, Natick...-Methyl-2,5-dimethoxyamphetamine (7395)... I Dimethyltryptamine (7435) I The company plans to...

  7. Space-time delta-sigma modulation for reception of multiple simultaneous independent RF beams

    NASA Astrophysics Data System (ADS)

    Rong, Guoguang; Black, Bruce A.; Siahmakoun, Azad Z.

    2005-09-01

    In this paper we introduce and analyze a multiple-RF-beam beamformer in receive mode utilizing the principle of space-time delta-sigma modulation. This principle is based on sampling input signals in both time and space and converting the sampled signals into a digital format by delta-sigma conversion. Noise shaping is achieved in 2D frequency domain. We show that the modulator can receive signals of narrow and wide bandwidths with steering capability, can receive multiple beams, and establish tradeoffs between sampling in time and in space. The ability of the modulator to trade off between time and space provides an effective way to sample high frequency RF signals without down conversion. In addition, a space-time delta-sigma modulator has better performance than a solely temporal delta-sigma modulator (for the same filter order), as is typically used in communication systems to digitize the down-converted analog signals.

  8. Differential Photoproduction Cross Sections of the Sigma0(1385), Lambda(1405), and Lambda(1520)

    SciTech Connect

    Moriya, Kei; Schumacher, Reinhard A.

    2013-10-01

    We report the exclusive photoproduction cross sections for the Sigma(1385), Lambda(1405), and Lambda(1520) in the reactions gamma + p -> K+ + Y* using the CLAS detector for energies from near the respective production thresholds up to a center-of-mass energy W of 2.85 GeV. The differential cross sections are integrated to give the total exclusive cross sections for each hyperon. Comparisons are made to current theoretical models based on the effective Lagrangian approach and fitted to previous data. The accuracy of these models is seen to vary widely. The cross sections for the Lambda(1405) region are strikingly different for the Sigma+pi-, Sigma0 pi0, and Sigma- pi+ decay channels, indicating the effect of isospin interference, especially at W values close to the threshold.

  9. Is Lebesgue measure the only [sigma]-finite invariant Borel measure?

    NASA Astrophysics Data System (ADS)

    Elekes, Marton; Keleti, Tamas

    2006-09-01

    S. Saks and recently R.D. Mauldin asked if every translation invariant [sigma]-finite Borel measure on is a constant multiple of Lebesgue measure. The aim of this paper is to investigate the versions of this question, since surprisingly the answer is "yes and no," depending on what we mean by Borel measure and by constant. According to a folklore result, if the measure is only defined for Borel sets, then the answer is affirmative. We show that if the measure is defined on a [sigma]-algebra containing the Borel sets, then the answer is negative. However, if we allow the multiplicative constant to be infinity, then the answer is affirmative in this case as well. Moreover, our construction also shows that an isometry invariant [sigma]-finite Borel measure (in the wider sense) on can be non-[sigma]-finite when we restrict it to the Borel sets.

  10. Distinguishing between chi and sigma phases in duplex stainless steels using potentiostatic etching

    SciTech Connect

    Jackson, E.M.L.E.M.; Visser, P.E. de . Physical Metallurgy Div.); Cornish, L.A. )

    1993-12-01

    A color interference film etching technique based on the principle of potentiostatic etching has been developed to distinguish, by optical metallography, between Cr-rich sigma and Mo-rich chi phases as well as with simultaneous identification of the ferrite and austenite phases in duplex stainless steels. The optical metallography results are confirmed by semiquantitative energy dispersive spectrometry analysis and back-scattered electron imaging. The technique is relatively simple and rapid, and makes use of low voltages and a hot etchant. Results have shown distinctively the sigma, chi, ferrite, and austenite phases, and enable observation of the microstructural development, morphology, and kinetics of formation of the phases in duplex alloys. The method, by giving excellent color contrast between sigma and chi, also facilitates quantitative image analysis of the sigma and chi volume fractions.

  11. The Statistical point of view of Quality: the Lean Six Sigma methodology.

    PubMed

    Bertolaccini, Luca; Viti, Andrea; Terzi, Alberto

    2015-04-01

    Six Sigma and Lean are two quality improvement methodologies. The Lean Six Sigma methodology is applicable to repetitive procedures. Therefore, the use of this methodology in the health-care arena has focused mainly on areas of business operations, throughput, and case management and has focused on efficiency outcomes. After the revision of methodology, the paper presents a brief clinical example of the use of Lean Six Sigma as a quality improvement method in the reduction of the complications during and after lobectomies. Using Lean Six Sigma methodology, the multidisciplinary teams could identify multiple modifiable points across the surgical process. These process improvements could be applied to different surgical specialties and could result in a measurement, from statistical point of view, of the surgical quality. PMID:25973253

  12. The Statistical point of view of Quality: the Lean Six Sigma methodology

    PubMed Central

    Viti, Andrea; Terzi, Alberto

    2015-01-01

    Six Sigma and Lean are two quality improvement methodologies. The Lean Six Sigma methodology is applicable to repetitive procedures. Therefore, the use of this methodology in the health-care arena has focused mainly on areas of business operations, throughput, and case management and has focused on efficiency outcomes. After the revision of methodology, the paper presents a brief clinical example of the use of Lean Six Sigma as a quality improvement method in the reduction of the complications during and after lobectomies. Using Lean Six Sigma methodology, the multidisciplinary teams could identify multiple modifiable points across the surgical process. These process improvements could be applied to different surgical specialties and could result in a measurement, from statistical point of view, of the surgical quality. PMID:25973253

  13. 78 FR 32458 - Manufacturer of Controlled Substances; Notice of Registration; Sigma Aldrich Research...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-30

    ... February 21, 2013, 78 FR 12102, Sigma ] Aldrich Research Biochemicals, Inc., 1-3 Strathmore Road, Natick... (TCP) I (7470). N-Benzylpiperazine (BZP) (7493) I Heroin (9200) I Normorphine (9313) I...

  14. 77 FR 31390 - Manufacturer of Controlled Substances; Notice of Registration; Sigma Aldrich Research...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-25

    ... February 6, 2012, 77 FR 5847, Sigma Aldrich Research Biochemicals, Inc., 1-3 Strathmore Road, Natick...-diisopropyltryptamine (7439)....... I 1- piperidine (7470)..... I N-Benzylpiperazine (7493) I Heroin (9200)...

  15. Topics in conformal invariance and generalized sigma models

    SciTech Connect

    Bernardo, L M

    1997-05-01

    This thesis consists of two different parts, having in common the fact that in both, conformal invariance plays a central role. In the first part, the author derives conditions for conformal invariance, in the large N limit, and for the existence of an infinite number of commuting classical conserved quantities, in the Generalized Thirring Model. The treatment uses the bosonized version of the model. Two different approaches are used to derive conditions for conformal invariance: the background field method and the Hamiltonian method based on an operator algebra, and the agreement between them is established. The author constructs two infinite sets of non-local conserved charges, by specifying either periodic or open boundary conditions, and he finds the Poisson Bracket algebra satisfied by them. A free field representation of the algebra satisfied by the relevant dynamical variables of the model is also presented, and the structure of the stress tensor in terms of free fields (and free currents) is studied in detail. In the second part, the author proposes a new approach for deriving the string field equations from a general sigma model on the world sheet. This approach leads to an equation which combines some of the attractive features of both the renormalization group method and the covariant beta function treatment of the massless excitations. It has the advantage of being covariant under a very general set of both local and non-local transformations in the field space. The author applies it to the tachyon, massless and first massive level, and shows that the resulting field equations reproduce the correct spectrum of a left-right symmetric closed bosonic string.

  16. Antagonism of sigma-1 receptors blocks compulsive-like eating.

    PubMed

    Cottone, Pietro; Wang, Xiaofan; Park, Jin Won; Valenza, Marta; Blasio, Angelo; Kwak, Jina; Iyer, Malliga R; Steardo, Luca; Rice, Kenner C; Hayashi, Teruo; Sabino, Valentina

    2012-11-01

    Binge eating disorder is an addiction-like disorder characterized by episodes of rapid and excessive food consumption within discrete periods of time which occur compulsively despite negative consequences. This study was aimed at determining whether antagonism of Sigma-1 receptors (Sig-1Rs) blocked compulsive-like binge eating. We trained male wistar rats to obtain a sugary, highly palatable diet (Palatable group) or a regular chow diet (Chow control group), for 1 h a day under fixed ratio 1 operant conditioning. Following intake stabilization, we evaluated the effects of the selective Sig-1R antagonist BD-1063 on food responding. Using a light/dark conflict test, we also tested whether BD-1063 could block the time spent and the food eaten in an aversive, open compartment, where the palatable diet was offered. Furthermore, we measured Sig-1R mRNA and protein expression in several brain areas of the two groups, 24 h after the last binge session. Palatable rats rapidly developed binge-like eating, escalating the 1 h intake by four times, and doubling the eating rate and the regularity of food responding, compared to Chow rats. BD-1063 dose-dependently reduced binge-like eating and the regularity of food responding, and blocked the increased eating rate in Palatable rats. In the light/dark conflict test, BD-1063 antagonized the increased time spent in the aversive compartment and the increased intake of the palatable diet, without affecting motor activity. Finally, Palatable rats showed reduced Sig-1R mRNA expression in prefrontal and anterior cingulate cortices, and a two-fold increase in Sig-1R protein expression in anterior cingulate cortex compared to control Chow rats. These findings suggest that the Sig-1R system may contribute to the neurobiological adaptations driving compulsive-like eating, opening new avenues of investigation towards pharmacologically treating binge eating disorder. PMID:22713906

  17. Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance

    PubMed Central

    Kabe, Yasuaki; Nakane, Takanori; Koike, Ikko; Yamamoto, Tatsuya; Sugiura, Yuki; Harada, Erisa; Sugase, Kenji; Shimamura, Tatsuro; Ohmura, Mitsuyo; Muraoka, Kazumi; Yamamoto, Ayumi; Uchida, Takeshi; Iwata, So; Yamaguchi, Yuki; Krayukhina, Elena; Noda, Masanori; Handa, Hiroshi; Ishimori, Koichiro; Uchiyama, Susumu; Kobayashi, Takuya; Suematsu, Makoto

    2016-01-01

    Progesterone-receptor membrane component 1 (PGRMC1/Sigma-2 receptor) is a haem-containing protein that interacts with epidermal growth factor receptor (EGFR) and cytochromes P450 to regulate cancer proliferation and chemoresistance; its structural basis remains unknown. Here crystallographic analyses of the PGRMC1 cytosolic domain at 1.95 Å resolution reveal that it forms a stable dimer through stacking interactions of two protruding haem molecules. The haem iron is five-coordinated by Tyr113, and the open surface of the haem mediates dimerization. Carbon monoxide (CO) interferes with PGRMC1 dimerization by binding to the sixth coordination site of the haem. Haem-mediated PGRMC1 dimerization is required for interactions with EGFR and cytochromes P450, cancer proliferation and chemoresistance against anti-cancer drugs; these events are attenuated by either CO or haem deprivation in cancer cells. This study demonstrates protein dimerization via haem–haem stacking, which has not been seen in eukaryotes, and provides insights into its functional significance in cancer. PMID:26988023

  18. Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance.

    PubMed

    Kabe, Yasuaki; Nakane, Takanori; Koike, Ikko; Yamamoto, Tatsuya; Sugiura, Yuki; Harada, Erisa; Sugase, Kenji; Shimamura, Tatsuro; Ohmura, Mitsuyo; Muraoka, Kazumi; Yamamoto, Ayumi; Uchida, Takeshi; Iwata, So; Yamaguchi, Yuki; Krayukhina, Elena; Noda, Masanori; Handa, Hiroshi; Ishimori, Koichiro; Uchiyama, Susumu; Kobayashi, Takuya; Suematsu, Makoto

    2016-01-01

    Progesterone-receptor membrane component 1 (PGRMC1/Sigma-2 receptor) is a haem-containing protein that interacts with epidermal growth factor receptor (EGFR) and cytochromes P450 to regulate cancer proliferation and chemoresistance; its structural basis remains unknown. Here crystallographic analyses of the PGRMC1 cytosolic domain at 1.95 Å resolution reveal that it forms a stable dimer through stacking interactions of two protruding haem molecules. The haem iron is five-coordinated by Tyr113, and the open surface of the haem mediates dimerization. Carbon monoxide (CO) interferes with PGRMC1 dimerization by binding to the sixth coordination site of the haem. Haem-mediated PGRMC1 dimerization is required for interactions with EGFR and cytochromes P450, cancer proliferation and chemoresistance against anti-cancer drugs; these events are attenuated by either CO or haem deprivation in cancer cells. This study demonstrates protein dimerization via haem-haem stacking, which has not been seen in eukaryotes, and provides insights into its functional significance in cancer. PMID:26988023

  19. Vibrational Properties of {alpha}- and {sigma}-phase Fe-Cr alloy.

    SciTech Connect

    Dubiel, S. M.; Cieslak, J.; Sturhahn, W.; Sternik, M.; Piekarz, P.; Stankov, S.; Parlinski, K.; AGH Univ. of Science and Technology; Polish Academy of Sciences; Karlsruher Inst. of Tech.

    2010-01-01

    Experimental and theoretical studies, of the Fe-partial phonon density of states (PDOS) for Fe{sub 52.5}Cr{sub 47.5} alloy having {alpha} and {sigma} phases were carried out. The former using the nuclear resonant inelastic x-ray scattering method, and the latter with the direct one. Characteristic features of PDOS, which distinguish one phase from the other, were revealed and successfully reproduced by the theory. Data pertinent to the dynamics such as the Lamb-Moessbauer factor, f, the kinetic energy per atom, E{sub k}, and the mean force constant, D, were directly derived, while vibrational specific heat at constant volume, C{sub V}, and vibrational entropy, S were calculated using the Fe partial PDOS. Based on the values of f and C{sub V}, we determined Debye temperatures, {Theta}{sub D}. An excellent agreement for some quantities derived from experiment and first-principles theory, like C{sub V} and quite good ones for others like D and S were obtained.

  20. DISK ASSEMBLY AND THE M {sub BH}-{sigma} {sub e} RELATION OF SUPERMASSIVE BLACK HOLES

    SciTech Connect

    Debattista, Victor P.; Kazantzidis, Stelios; Van den Bosch, Frank C. E-mail: stelios@mps.ohio-state.edu

    2013-03-01

    Recent Hubble Space Telescope observations have revealed that a majority of active galactic nuclei (AGNs) at z {approx} 1-3 are resident in isolated disk galaxies, contrary to the usual expectation that AGNs are triggered by mergers. Here we develop a new test of the cosmic evolution of supermassive black holes (SMBHs) in disk galaxies by considering the local population of SMBHs. We show that substantial SMBH growth in spiral galaxies is required as disks assemble. SMBHs exhibit a tight relation between their mass and the velocity dispersion of the spheroid within which they reside, the M {sub .}-{sigma} {sub e} relation. In disk galaxies the bulge is the spheroid of interest. We explore the evolution of the M {sub .}-{sigma} {sub e} relation when bulges form together with SMBHs on the M {sub .}-{sigma} {sub e} relation and then slowly re-form a disk around them. The formation of the disk compresses the bulge, raising its {sigma} {sub e}. We present evidence for such compression in the form of larger velocity dispersion of classical bulges compared with elliptical galaxies at the same mass. This compression leads to an offset in the M {sub .}-{sigma} {sub e} relation if it is not accompanied by an increased M {sub .}. We quantify the expected offset based on photometric data and show that, on average, SMBHs must grow by {approx}50%-65% just to remain on the M {sub .}-{sigma} {sub e} relation. We find no significant offset in the M {sub .}-{sigma} {sub e} relations of classical bulges and of ellipticals, implying that SMBHs have been growing along with disks. Our simulations demonstrate that SMBH growth is necessary for the local population of disk galaxies to have remained on the M {sub .}-{sigma} {sub e} relation.

  1. Comparison of Sigma-Point and Extended Kalman Filters on a Realistic Orbit Determination Scenario

    NASA Technical Reports Server (NTRS)

    Gaebler, John; Hur-Diaz. Sun; Carpenter, Russell

    2010-01-01

    Sigma-point filters have received a lot of attention in recent years as a better alternative to extended Kalman filters for highly nonlinear problems. In this paper, we compare the performance of the additive divided difference sigma-point filter to the extended Kalman filter when applied to orbit determination of a realistic operational scenario based on the Interstellar Boundary Explorer mission. For the scenario studied, both filters provided equivalent results. The performance of each is discussed in detail.

  2. Purification, molecular cloning, and expression of the mammalian sigma1-binding site.

    PubMed Central

    Hanner, M; Moebius, F F; Flandorfer, A; Knaus, H G; Striessnig, J; Kempner, E; Glossmann, H

    1996-01-01

    Sigma-ligands comprise several chemically unrelated drugs such as haloperidol, pentazocine, and ditolylguanidine, which bind to a family of low molecular mass proteins in the endoplasmic reticulum. These so-called sigma-receptors are believed to mediate various pharmacological effects of sigma-ligands by as yet unknown mechanisms. Based on their opposite enantioselectivity for benzomorphans and different molecular masses, two subtypes are differentiated. We purified the sigma1-binding site as a single 30-kDa protein from guinea pig liver employing the benzomorphan(+)[3H]pentazocine and the arylazide (-)[3H]azidopamil as specific probes. The purified (+)[3H]pentazocine-binding protein retained its high affinity for haloperidol, pentazocine, and ditolylguanidine. Partial amino acid sequence obtained after trypsinolysis revealed no homology to known proteins. Radiation inactivation of the pentazocine-labeled sigma1-binding site yielded a molecular mass of 24 +/- 2 kDa. The corresponding cDNA was cloned using degenerate oligonucleotides and cDNA library screening. Its open reading frame encoded a 25.3-kDa protein with at least one putative transmembrane segment. The protein expressed in yeast cells transformed with the cDNA showed the pharmacological characteristics of the brain and liver sigma1-binding site. The deduced amino acid sequence was structurally unrelated to known mammalian proteins but it shared homology with fungal proteins involved in sterol synthesis. Northern blots showed high densities of the sigma1-binding site mRNA in sterol-producing tissues. This is also in agreement with the known ability of sigma1-binding sites to interact with steroids, such as progesterone. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8755605

  3. Sigma-2 receptor binding is decreased in female, but not male, APP/PS1 mice.

    PubMed

    Sahlholm, Kristoffer; Liao, Fan; Holtzman, David M; Xu, Jinbin; Mach, Robert H

    2015-05-01

    The sigma-2 receptor is a steroid-binding membrane-associated receptor which has been implicated in cell survival. Sigma-2 has recently been shown to bind amyloid-β (Aβ) oligomers in Alzheimer's disease (AD) brain. Furthermore, blocking this interaction was shown to prevent or reverse the effects of Aβ to cause cognitive impairment in mouse models and synaptic loss in neuronal cultures. In the present work, the density of sigma-2 receptors was measured in a double transgenic mouse model of amyloid-β deposition (APP/PS1). Comparisons were made between males and females and between transgenic and wt animals. Sigma-2 receptor density was assessed by quantitative autoradiography performed on coronal brain slices using [(3)H]N-[4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butyl]-2-methoxy-5-methyl-benzamide ([(3)H]RHM-1), which has a 300-fold selectivity for the sigma-2 receptor over the sigma-1 receptor. The translocator protein of 18 kDa (TSPO) is expressed on activated microglia and is a marker for neuroinflammation. TSPO has been found to be upregulated in neurodegenerative disorders, including AD. Therefore, in parallel with the sigma-2 autoradiography experiments, we measured TSPO expression using the selective radioligand, [(3)H]PBR28. We also quantified Aβ plaque burden in the same animals using a monoclonal antibody raised against aggregated Aβ. Sigma-2 receptor density was significantly decreased in piriform and motor cortices as well as striata of 16-month old female, but not male, APP/PS1 mice as compared to their wt counterparts. [(3)H]PBR28 binding and immunostaining for Aβ plaques were significantly increased in piriform and motor cortices of both male and female transgenic mice. In striatum however, significant increases were observed only in females. PMID:25796326

  4. The structural significance of HAZ sigma phase formation in welded 25%Cr super duplex pipework

    SciTech Connect

    Wiesner, C.S.; Garwood, S.J.; Bowden, P.L.

    1993-12-31

    The welding of 25%Cr duplex stainless steel can lead to the formation of sigma phase in both weld metal and heat affected zone (HAZ) regions. It has generally been accepted that this can be avoided by the adoption of appropriate welding procedure controls, generally aimed at reducing heat input and promoting rapid cooling rates. However, experience during pipe spool fabrication for the Marathon East Brae Project has shown that it is extremely difficult to satisfy a welding specification requiring sigma free HAZs. This has proved a particular problem with thin wall pipe welds made in the 2G/5G or 6G fixed positions, where the joint geometry reduces heat flow away from the weld and welding conditions tend to result in the use of higher heat inputs. This paper examines the effect of sigma phase on the fracture toughness of 25%Cr super duplex steel (UNS S32760). It is shown that the CTOD toughness at {minus}20 C decreases as soon as any sigma phase is present and continues to decrease with increasing sigma levels. The toughness of the sigmatized specimens produced by heat treatment was shown to be conservative compared to the toughness measured in the HAZ of 14.2mm and 7.1mm thick pipe weldments, made with welding parameters chosen to enhance HAZ sigma phase formation. Based on the CTOD versus percent sigma level relationship derived from the laboratory specimens, fracture assessment calculations of tolerable flaw sizes were performed. These demonstrated that under the severest design conditions, assuming the maximum flaw sizes which could remain undetected in the pipework, sigma levels up to 2.5% can be tolerated safely. The conservatism of the fracture assessments for predicting the performance of weldments was demonstrated by full scale tensile testing of 2 inch nominal bore x 2.77 mm wall thickness pipe butt welds containing through-thickness circumferential fatigue cracks located in the sigmatized HAZ.

  5. Use of Six Sigma for eliminating missed opportunities for prevention services.

    PubMed

    Gittner, LisaAnn S; Husaini, Baqar A; Hull, Pamela C; Emerson, Janice S; Tropez-Sims, Suzanne; Reece, Michelle C; Zoorob, Roger; Levine, Robert S

    2015-01-01

    Delivery of primary care preventative services can be significantly increased utilizing Six Sigma methods. Missed preventative service opportunities were compared in the study clinic with the community clinic in the same practice. The study clinic had 100% preventative services, compared with only 16.3% in the community clinic. Preventative services can be enhanced to Six Sigma quality when the nurse executive and medical staff agree on a single standard of nursing care executed via standing orders. PMID:25629453

  6. Sigma E Regulators Control Hemolytic Activity and Virulence in a Shrimp Pathogenic Vibrio harveyi

    PubMed Central

    Rattanama, Pimonsri; Thompson, Janelle R.; Kongkerd, Natthawan; Srinitiwarawong, Kanchana; Vuddhakul, Varaporn; Mekalanos, John J.

    2012-01-01

    Members of the genus Vibrio are important marine and aquaculture pathogens. Hemolytic activity has been identified as a virulence factor in many pathogenic vibrios including V. cholerae, V. parahaemolyticus, V. alginolyticus, V. harveyi and V. vulnificus. We have used transposon mutagenesis to identify genes involved in the hemolytic activity of shrimp-pathogenic V. harveyi strain PSU3316. Out of 1,764 mutants screened, five mutants showed reduced hemolytic activity on sheep blood agar and exhibited virulence attenuation in shrimp (Litopenaeus vannamei). Mutants were identified by comparing transposon junction sequences to a draft of assembly of the PSU3316 genome. Surprisingly none of the disrupted open reading frames or gene neighborhoods contained genes annotated as hemolysins. The gene encoding RseB, a negative regulator of the sigma factor (σE), was interrupted in 2 out of 5 transposon mutants, in addition, the transcription factor CytR, a threonine synthetase, and an efflux-associated cytoplasmic protein were also identified. Knockout mutations introduced into the rpoE operon at the rseB gene exhibited low hemolytic activity in sheep blood agar, and were 3-to 7-fold attenuated for colonization in shrimp. Comparison of whole cell extracted proteins in the rseB mutant (PSU4030) to the wild-type by 2-D gel electrophoresis revealed 6 differentially expressed proteins, including two down-regulated porins (OmpC-like and OmpN) and an upregulated protease (DegQ) which have been associated with σE in other organisms. Our study is the first report linking hemolytic activity to the σE regulators in pathogenic Vibrio species and suggests expression of this virulence-linked phenotype is governed by multiple regulatory pathways within the V. harveyi. PMID:22384269

  7. Targeting ligand-operated chaperone sigma-1 receptors in the treatment of neuropsychiatric disorders

    PubMed Central

    Teruo, Hayashi; Shang-Yi, Tsai; Tomohisa, Mori; Michiko, Fujimoto; Tsung-Ping, Su

    2011-01-01

    Introduction Current conventional therapeutic drugs for the treatment of psychiatric or neurodegenerative disorders have certain limitations of use. Psychotherapeutic drugs such as typical and atypical antipsychotics, tricyclic antidepressants, and selective monoamine reuptake inhibitors, aim to normalize the hyper- or hypo-neurotransmission of monoaminergic systems. Despite their great contribution to the outcomes of psychiatric patients, these agents often exert severe side effects and require chronic treatments to promote amelioration of symptoms. Furthermore, drugs available for the treatment of neurodegenerative disorders are severely limited. Areas covered This review discusses recent evidence that has shed light on sigma-1 receptor ligands, which may serve as a new class of antidepressants or neuroprotective agents. Sigma-1 receptors are novel ligand-operated molecular chaperones regulating a variety of signal transduction, ER stress, cellular redox, cellular survival, and synaptogenesis. Selective sigma-1 receptor ligands exert rapid antidepressant-like, anxiolytic, antinociceptive and robust neuroprotective actions in preclinical studies. The review also looks at recent studies which suggest that reactive oxygen species might play a crucial role as signal integrators at the downstream of Sig-1Rs Expert opinion The significant advances in sigma receptor research in the last decade have begun to elucidate the intracellular signal cascades upstream and downstream of sigma-1 receptors. The novel ligand-operated properties of the sigma-1 receptor chaperone may enable a variety of interventions by which stress-related cellular systems are pharmacologically controlled. PMID:21375464

  8. The Applicability of Lean and Six Sigma Techniques to Clinical and Translational Research

    PubMed Central

    Schweikhart, Sharon A.; Dembe, Allard E

    2010-01-01

    Background Lean and Six Sigma are business management strategies commonly used in production industries to improve process efficiency and quality. During the past decade, these process improvement techniques increasingly have been applied outside of the manufacturing sector, for example, in health care and in software development. This article concerns the potential use of Lean and Six Sigma to improve the processes involved in clinical and translational research. Improving quality, avoiding delays and errors, and speeding up the time to implementation of biomedical discoveries are prime objectives of the NIH Roadmap for Biomedical Research and the NIH Clinical and Translational Science Award (CTSA) program. Methods This article presents a description of the main principles, practices, and methodologies used in Lean and Six Sigma. Available literature involving applications of Lean and Six Sigma to health care, laboratory science, and clinical and translational research is reviewed. Specific issues concerning the use of these techniques in different phases of translational research are identified. Results Examples are provided of Lean and Six Sigma applications that are being planned at a current CTSA site, which could potentially be replicated elsewhere. We describe how different process improvement approaches are best adapted for particularly translational research phases. Conclusions Lean and Six Sigma process improvement methodologies are well suited to help achieve NIH’s goal of making clinical and translational research more efficient and cost-effective, enhancing the quality of the research, and facilitating the successful adoption of biomedical research findings into practice. PMID:19730130

  9. [The use of sigma-delta analog-digital conversion in multichannel electrocardiographs].

    PubMed

    Kurikov, S F; Prilutskiĭ, D A; Selishchev, S V

    1997-01-01

    With advances in the manufacture of super great integrated circuits, a commercially available element base that realizes the sigma-delta (sigma-delta) analog-to-digital conversion principle in one microcircuit has appeared. The sigma-delta analog-to-digital converters (ADC) have a high resolving power (above 12 bits), they are largely based on the signal digital filtration principles, which may moderate requirements for the analog filtration of signals and use direct-current amplifiers as alternatives to instrument ones. For electrocardiograph operation, the sigma-delta ADC of an AD 7716 (Analog Devices) with 22 bits were used in this study. The use of sigma-delta ADC in the electrocardiographs has been shown to be a rather useful alternative of traditional ADC. Moreover, sigma-delta ADC may be also useful for other systems for collecting and processing biomedical signals which are close in their requirements for a frequency range and a dynamic range, i.e. encephalographic, myographic, rheographic and other input signals. PMID:9379865

  10. Crucial interactions between selective serotonin uptake inhibitors and sigma-1 receptor in heart failure.

    PubMed

    Bhuiyan, Md Shenuarin; Tagashira, Hideaki; Fukunaga, Kohji

    2013-01-01

    Depression is associated with a substantial increase in the risk of developing heart failure and is independently associated with increased cardiovascular morbidity and mortality. Inversely, cardiovascular disease can lead to severe depression. Thus, therapy with selective serotonin reuptake inhibitors (SSRIs) is strongly recommended to reduce cardiovascular disease-induced morbidity and mortality. However, molecular mechanisms to support evidence-based SSRI treatment of cardiovascular disease have not been elucidated. We recently found very high expression of the sigma-1 receptor, an orphan receptor, in rat heart tissue and defined the cardiac sigma-1 receptor as a direct SSRI target in eliciting cardioprotection in both pressure overload (PO)induced and transverse aortic constriction (TAC)-induced myocardial hypertrophy models in rodents. Our findings suggest that SSRIs such as fluvoxamine protect against PO- and TAC-induced cardiac dysfunction by upregulating sigma-1 receptor expression and stimulating sigma-1 receptor-mediated Akt-eNOS signaling. Here, we discuss the association of depression and cardiovascular diseases, the protective mechanism of SSRIs in heart failure patients, and the pathophysiological relevance of sigma-1 receptors to progression of heart failure. These findings should promote development of clinical therapeutics targeting the sigma-1 receptor in cardiovascular diseases. PMID:23428811

  11. [Laser fluorescence excited spectrum of NO via alpha2sigma<--chi2pi transition].

    PubMed

    Zhang, Lian-shui; Zhang, Gui-yin; Zhao, Xiao-hui; Yang, Xiao-dong; Li, Yi

    2004-06-01

    Two-photon fluorescence excited spectrum of NO induced by Nd: YAG laser pumped optical parameter generator/amplifier as excitation source was obtained in the range of 420-472 nm. With this technique, the structure of the energy levels of NO molecule in alpha2sigma electronic state was investigated. The peaks of the spectrum were attributed to alpha2sigma(v' = 0,1)<--chi2pi(v" = 0) transition. The near square dependence of fluorescence signal on the laser intensity indicates a two-photon process. The ground-vibrational-state oscillation frequency and the force constant of alpha2sigma state were calculated. The fluorescence lifetime of alpha2sigma(v' = 0) state under the pressure of 266 Pa was also obtained by measuring fluorescence decay curve of alpha2sigma(v' = 0) states. It is about 53.76 ns. Fitting the curve of the fluorescence radiant lifetime versus pressure, the spontaneous radiant lifetimes and the rate coefficient of nonradiative transition relaxation of alpha2sigma(v' = 0,1) states were deduced. PMID:15766171

  12. Characterization and Evaluation of Two Novel Fluorescent Sigma-2 Receptor Ligands as Proliferation Probes

    PubMed Central

    Zeng, Chenbo; Vangveravong, Suwanna; Jones, Lynne A.; Hyrc, Krzysztof; Chang, Katherine C.; Xu, Jinbin; Rothfuss, Justin M.; Goldberg, Mark P.; Hotchkiss, Richard S.; Mach, Robert H.

    2015-01-01

    We synthesized and characterized two novel fluorescent sigma-2 receptor selective ligands, SW120 and SW116, and evaluated these ligands as potential probes for imaging cell proliferation. Both ligands are highly selective for sigma-2 receptors versus sigma-1 receptors. SW120 and SW116 were internalized into MDA-MB-435 cells, and 50% of the maximum fluorescent intensity was reached in 11 and 24 minutes, respectively. In vitro studies showed that 50% of SW120 or SW116 washed out of cells in 1 hour. The internalization of SW120 was reduced ≈30% by phenylarsine oxide, an inhibitor of endocytosis, suggesting that sigma-2 ligands are internalized, in part, by an endocytotic pathway. Subcellular localization studies using confocal and two-photon microscopy showed that SW120 and SW116 partially colocalized with fluorescent markers of mitochondria, endoplasmic reticulum, lysosomes, and the plasma membrane, suggesting that sigma-2 receptors localized to the cytoplasmic organelles and plasma membrane. SW120 did not colocalize with the nuclear dye 4′,6-diamidino-2-phenylindole. In vivo studies showed that the uptake of SW120 in solid tumors and peripheral blood mononuclear cells of mice positively correlated with the expression level of the cell proliferation marker Ki-67, suggesting that sigma-2 fluorescent probes may be used to image cell proliferation in mice. PMID:22201533

  13. Transcriptome Profiling of the Endophyte Burkholderia phytofirmans PsJN Indicates Sensing of the Plant Environment and Drought Stress

    PubMed Central

    Sheibani-Tezerji, Raheleh; Rattei, Thomas; Sessitsch, Angela; Trognitz, Friederike

    2015-01-01

    ABSTRACT It is widely accepted that bacterial endophytes actively colonize plants, interact with their host, and frequently show beneficial effects on plant growth and health. However, the mechanisms of plant-endophyte communication and bacterial adaption to the plant environment are still poorly understood. Here, whole-transcriptome sequencing of B. phytofirmans PsJN colonizing potato (Solanum tuberosum L.) plants was used to analyze in planta gene activity and the response of strain PsJN to plant stress. The transcriptome of PsJN colonizing in vitro potato plants showed a broad array of functionalities encoded in the genome of strain PsJN. Transcripts upregulated in response to plant drought stress were mainly involved in transcriptional regulation, cellular homeostasis, and the detoxification of reactive oxygen species, indicating an oxidative stress response in PsJN. Genes with modulated expression included genes for extracytoplasmatic function (ECF) group IV sigma factors. These cell surface signaling elements allow bacteria to sense changing environmental conditions and to adjust their metabolism accordingly. TaqMan quantitative PCR (TaqMan-qPCR) was performed to identify ECF sigma factors in PsJN that were activated in response to plant stress. Six ECF sigma factor genes were expressed in PsJN colonizing potato plants. The expression of one ECF sigma factor was upregulated whereas that of another one was downregulated in a plant genotype-specific manner when the plants were stressed. Collectively, our study results indicate that endophytic B. phytofirmans PsJN cells are active inside plants. Moreover, the activity of strain PsJN is affected by plant drought stress; it senses plant stress signals and adjusts its gene expression accordingly. PMID:26350963

  14. The low-lying {pi}{sigma}* state and its role in the intramolecular charge transfer of aminobenzonitriles and aminobenzethyne

    SciTech Connect

    Lee, Jae-Kwang; Fujiwara, Takashige; Kofron, William G.; Zgierski, Marek Z.; Lim, Edward C.

    2008-04-28

    Electronic absorption spectra of the low-lying {pi}{pi}* and {pi}{sigma}* states of several aminobenzonitriles and 4-dimethylaminobenzethyne have been studied by time-resolved transient absorption and time-dependent density functional theory calculation. In acetonitrile, the lifetime of the {pi}{sigma}*-state absorption is very short (picoseconds or subpicosecond) for molecules that exhibit intramolecular charge transfer (ICT), and very long (nanoseconds) for those that do not. Where direct comparison of the temporal characteristics of the {pi}{sigma}*-state and the ICT-state transients could be made, the formation rate of the ICT state is identical to the decay rate of the {pi}{sigma}* state within the experimental uncertainty. These results are consistent with the {pi}{sigma}*-mediated ICT mechanism, L{sub a} ({pi}{pi}*){yields}{pi}{sigma}*{yields}ICT, in which the decay rate of the {pi}{sigma}* state is determined by the rate of the solvent-controlled {pi}{sigma}*{yields}ICT charge-shift reaction. The {pi}{pi}*{yields}{pi}{sigma}* state crossing does not occur in 3-dimethylaminobenzonitrile or 2-dimethylaminobenzonitrile, as predicted by the calculation, and 4-aminobenzonitrile and 4-dimethylaminobenzethyne does not exhibit the ICT reaction, consistent with the higher energy of the ICT state relative to the {pi}{sigma}* state.

  15. UDP-glucose is a potential intracellular signal molecule in the control of expression of sigma S and sigma S-dependent genes in Escherichia coli.

    PubMed Central

    Böhringer, J; Fischer, D; Mosler, G; Hengge-Aronis, R

    1995-01-01

    The sigma S subunit of RNA polymerase is the master regulator of a regulatory network that controls stationary-phase induction as well as osmotic regulation of many genes in Escherichia coli. In an attempt to identify additional regulatory components in this network, we have isolated Tn10 insertion mutations that in trans alter the expression of osmY and other sigma S-dependent genes. One of these mutations conferred glucose sensitivity and was localized in pgi (encoding phosphoglucose isomerase). pgi::Tn10 strains exhibit increased basal levels of expression of osmY and otsBA in exponentially growing cells and reduced osmotic inducibility of these genes. A similar phenotype was also observed for pgm and galU mutants, which are deficient in phosphoglucomutase and UDP-glucose pyrophosphorylase, respectively. This indicates that the observed effects on gene expression are related to the lack of UDP-glucose (or a derivative thereof), which is common to all three mutants. Mutants deficient in UDP-galactose epimerase (galE mutants) and trehalose-6-phosphate synthase (otsA mutants) do not exhibit such an effect on gene expression, and an mdoA mutant that is deficient in the first step of the synthesis of membrane-derived oligosaccharides, shows only a partial increase in the expression of osmY. We therefore propose that the cellular content of UDP-glucose serves as an internal signal that controls expression of osmY and other sigma S-dependent genes. In addition, we demonstrate that pgi, pgm, and galU mutants contain increased levels of sigma S during steady-state growth, indicating that UDP-glucose interferes with the expression of sigma S itself. PMID:7814331

  16. Bacillus cereus ATCC 14579 RpoN (Sigma 54) Is a Pleiotropic Regulator of Growth, Carbohydrate Metabolism, Motility, Biofilm Formation and Toxin Production

    PubMed Central

    Hayrapetyan, Hasmik; Tempelaars, Marcel; Nierop Groot, Masja; Abee, Tjakko

    2015-01-01

    Sigma 54 is a transcriptional regulator predicted to play a role in physical interaction of bacteria with their environment, including virulence and biofilm formation. In order to study the role of Sigma 54 in Bacillus cereus, a comparative transcriptome and phenotypic study was performed using B. cereus ATCC 14579 WT, a markerless rpoN deletion mutant, and its complemented strain. The mutant was impaired in many different cellular functions including low temperature and anaerobic growth, carbohydrate metabolism, sporulation and toxin production. Additionally, the mutant showed lack of motility and biofilm formation at air-liquid interphase, and this correlated with absence of flagella, as flagella staining showed only WT and complemented strain to be highly flagellated. Comparative transcriptome analysis of cells harvested at selected time points during growth in aerated and static conditions in BHI revealed large differences in gene expression associated with loss of phenotypes, including significant down regulation of genes in the mutant encoding enzymes involved in degradation of branched chain amino acids, carbohydrate transport and metabolism, flagella synthesis and virulence factors. Our study provides evidence for a pleiotropic role of Sigma 54 in B. cereus supporting its adaptive response and survival in a range of conditions and environments. PMID:26241851

  17. Antitussive activity of sigma-1 receptor agonists in the guinea-pig

    PubMed Central

    Brown, Claire; Fezoui, Malika; Selig, William M; Schwartz, Carl E; Ellis, James L

    2003-01-01

    Current antitussive medications have limited efficacy and often contain the opiate-like agent dextromethorphan (DEX). The mechanism whereby DEX inhibits cough is ill defined. DEX displays affinity at both NMDA and sigma receptors, suggesting that the antitussive activity may involve central or peripheral activity at either of these receptors. This study examined and compared the antitussive activity of DEX and various putative sigma receptor agonists in the guinea-pig citric-acid cough model. Intraperitoneal (i.p.) administration of DEX (30 mg kg−1) and the sigma-1 agonists SKF-10,047 (1–5 mg kg−1), Pre-084 (5 mg kg−1), and carbetapentane (1–5 mg kg−1) inhibited citric-acid-induced cough in guinea-pigs. Intraperitoneal administration of a sigma-1 antagonist, BD 1047 (1–5 mg kg−1), reversed the inhibition of cough elicited by SKF-10,047. In addition, two structurally dissimilar sigma agonists SKF-10,047 (1 mg ml−1) and Pre-084 (1 mg ml−1) inhibited cough when administered by aerosol. Aerosolized BD 1047 (1 mg ml−1, 30 min) prevented the antitussive action of SKF-10,047 (5 mg kg−1) or DEX (30 mg kg−1) given by i.p. administration and, likewise, i.p. administration of BD 1047 (5 mg kg−1) prevented the antitussive action of SKF-10,047 given by aerosol (1 mg ml−1). These results therefore support the argument that antitussive effects of DEX may be mediated via sigma receptors, since both systemic and aerosol administration of sigma-1 receptor agonists inhibit citric-acid-induced cough in guinea-pigs. While significant systemic exposure is possible with aerosol administration, the very low doses administered (estimated <0.3 mg kg−1) suggest that there may be a peripheral component to the antitussive effect. PMID:14691051

  18. Selective sigma-2 ligands preferentially bind to pancreatic adenocarcinomas: applications in diagnostic imaging and therapy

    PubMed Central

    Kashiwagi, Hiroyuki; McDunn, Jonathan E; Simon, Peter O; Goedegebuure, Peter S; Xu, Jinbin; Jones, Lynne; Chang, Katherine; Johnston, Fabian; Trinkaus, Kathryn; Hotchkiss, Richard S; Mach, Robert H; Hawkins, William G

    2007-01-01

    Background Resistance to modern adjuvant treatment is in part due to the failure of programmed cell death. Therefore the molecules that execute the apoptotic program are potential targets for the development of anti-cancer therapeutics. The sigma-2 receptor has been found to be over-expressed in some types of malignant tumors, and, recently, small molecule ligands to the sigma-2 receptor were found to induce cancer cell apoptosis. Results The sigma-2 receptor was expressed at high levels in both human and murine pancreas cancer cell lines, with minimal or limited expression in normal tissues, including: brain, kidney, liver, lung, pancreas and spleen. Micro-PET imaging was used to demonstrate that the sigma-2 receptor was preferentially expressed in tumor as opposed to normal tissues in pancreas tumor allograft-bearing mice. Two structurally distinct sigma-2 receptor ligands, SV119 and WC26, were found to induce apoptosis to mice and human pancreatic cancer cells in vitro and in vivo. Sigma-2 receptor ligands induced apoptosis in a dose dependent fashion in all pancreatic cell lines tested. At the highest dose tested (10 μM), all sigma-2 receptor ligands induced 10–20% apoptosis in all pancreatic cancer cell lines tested (p < 0.05). In pancreas tumor allograft-bearing mice, a single bolus dose of WC26 caused approximately 50% apoptosis in the tumor compared to no appreciable apoptosis in tumor-bearing, vehicle-injected control animals (p < 0.0001). WC26 significantly slowed tumor growth after a 5 day treatment compared to vehicle-injected control animals (p < 0.0001) and blood chemistry panels suggested that there is minimal peripheral toxicity. Conclusion We demonstrate a novel therapeutic strategy that induces a significant increase in pancreas cancer cell death. This strategy highlights a new potential target for the treatment of pancreas cancer, which has little in the way of effective treatments. PMID:17631687

  19. The origin of aromaticity: important role of the sigma framework in benzene.

    PubMed

    Kovacević, Borislav; Barić, Danijela; Maksić, Zvonimir B; Müller, Thomas

    2004-09-20

    The physical nature of aromaticity is addressed at a high ab initio level. It is conclusively shown that the extrinsic aromatic stabilization energy of benzene E(ease)B, estimated relative to its linear polyene counterpart(s), is very well-reproduced at the Hartree-Fock (HF) level. This is a consequence of the fact that the contributions arising from the zero-point vibrational energy (ZPVE) and electron correlation are rather small. More specifically, they yield together 2.0 kcalmol(-1) to the destabilization of benzene. A careful scrutiny of the HF energies by virial theorem shows further that the kinetic energies of the sigma and pi electrons E(T)HF(sigma) and E(T)HF(pi) are strictly additive in the gauge linear zig-zag polyenes, which also holds for their sum Et(T)HF This finding has the important corollary that E(ease)B is little dependent on the choice of the homodesmic reactions involving zig-zag polyenes. A detailed physical analysis of the sigma- and pi-electron contributions to extrinsic aromaticity requires explicit introduction of the potential energy terms Vne, Vee, and Vnn, which signify Coulomb interactions between the electrons and the nuclei. The Vee term involves repulsive interaction Vee(sigmapi) between the sigma and pi electrons, which cannot be unequivocally resolved into sigma and pi contributions. The same holds for the Vnn energy, which implicitly depends on the electron density distribution via the Born-Oppenheimer (BO) potential energy surface. Several possibilities for partitioning Vee(sigmapi) and Vnn terms into sigma and pi components are examined. It is argued that the stockholder principle is the most realistic, which strongly indicates that E(ease)B is a result of favorable sigma-framework interactions. In contrast, the pi-electron framework prefers the open-chain linear polyenes. PMID:15503393

  20. Contribution of Flagellar Sigma Factor (FliA) to Virulence of Dickeya Dadantii

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ability to move in a directed manner affords advantages to host-adapted bacteria. This includes the ability to move toward a preferred host, access to infection sites, and escape back into the environment. The best understood flagella regulatory pathways are the transcriptional hierarchies of Es...