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Sample records for ecf sigma factor

  1. Regulation of antimicrobial resistance by extracytoplasmic function (ECF) sigma factors.

    PubMed

    Woods, Emily C; McBride, Shonna M

    2017-01-30

    Extracytoplasmic function (ECF) sigma factors are a subfamily of σ(70) sigma factors that activate genes involved in stress-response functions. In many bacteria, ECF sigma factors regulate resistance to antimicrobial compounds. This review will summarize the ECF sigma factors that regulate antimicrobial resistance in model organisms and clinically relevant pathogens.

  2. Characterization of five ECF sigma factors in the genome of Pseudomonas syringae pv. syringae B728a.

    PubMed

    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.

  3. Canonical and non-canonical EcfG sigma factors control the general stress response in Rhizobium etli.

    PubMed

    Jans, Ann; Vercruysse, Maarten; Gao, Shanjun; Engelen, Kristof; Lambrichts, Ivo; Fauvart, Maarten; Michiels, Jan

    2013-12-01

    A core component of the α-proteobacterial general stress response (GSR) is the extracytoplasmic function (ECF) sigma factor EcfG, exclusively present in this taxonomic class. Half of the completed α-proteobacterial genome sequences contain two or more copies of genes encoding σ(EcfG) -like sigma factors, with the primary copy typically located adjacent to genes coding for a cognate anti-sigma factor (NepR) and two-component response regulator (PhyR). So far, the widespread occurrence of additional, non-canonical σ(EcfG) copies has not satisfactorily been explained. This study explores the hierarchical relation between Rhizobium etli σ(EcfG1) and σ(EcfG2) , canonical and non-canonical σ(EcfG) proteins, respectively. Contrary to reports in other species, we find that σ(EcfG1) and σ(EcfG2) act in parallel, as nodes of a complex regulatory network, rather than in series, as elements of a linear regulatory cascade. We demonstrate that both sigma factors control unique yet also shared target genes, corroborating phenotypic evidence. σ(EcfG1) drives expression of rpoH2, explaining the increased heat sensitivity of an ecfG1 mutant, while katG is under control of σ(EcfG2) , accounting for reduced oxidative stress resistance of an ecfG2 mutant. We also identify non-coding RNA genes as novel σ(EcfG) targets. We propose a modified model for GSR regulation in R. etli, in which σ(EcfG1) and σ(EcfG2) function largely independently. Based on a phylogenetic analysis and considering the prevalence of α-proteobacterial genomes with multiple σ(EcfG) copies, this model may also be applicable to numerous other species.

  4. A Novel Extracytoplasmic Function (ECF) Sigma Factor Regulates Virulence in Pseudomonas aeruginosa

    PubMed Central

    Llamas, María A.; van der Sar, Astrid; Chu, Byron C. H.; Sparrius, Marion; Vogel, Hans J.; Bitter, Wilbert

    2009-01-01

    Next to the two-component and quorum sensing systems, cell-surface signaling (CSS) has been recently identified as an important regulatory system in Pseudomonas aeruginosa. CSS systems sense signals from outside the cell and transmit them into the cytoplasm. They generally consist of a TonB-dependent outer membrane receptor, a sigma factor regulator (or anti-sigma factor) in the cytoplasmic membrane, and an extracytoplasmic function (ECF) sigma factor. Upon perception of the extracellular signal by the receptor the ECF sigma factor is activated and promotes the transcription of a specific set of gene(s). Although most P. aeruginosa CSS systems are involved in the regulation of iron uptake, we have identified a novel system involved in the regulation of virulence. This CSS system, which has been designated PUMA3, has a number of unusual characteristics. The most obvious difference is the receptor component which is considerably smaller than that of other CSS outer membrane receptors and lacks a β-barrel domain. Homology modeling of PA0674 shows that this receptor is predicted to be a bilobal protein, with an N-terminal domain that resembles the N-terminal periplasmic signaling domain of CSS receptors, and a C-terminal domain that resembles the periplasmic C-terminal domains of the TolA/TonB proteins. Furthermore, the sigma factor regulator both inhibits the function of the ECF sigma factor and is required for its activity. By microarray analysis we show that PUMA3 regulates the expression of a number of genes encoding potential virulence factors, including a two-partner secretion (TPS) system. Using zebrafish (Danio rerio) embryos as a host we have demonstrated that the P. aeruginosa PUMA3-induced strain is more virulent than the wild-type. PUMA3 represents the first CSS system dedicated to the transcriptional activation of virulence functions in a human pathogen. PMID:19730690

  5. Bacillus subtilis extracytoplasmic function (ECF) sigma factors and defense of the cell envelope

    PubMed Central

    Helmann, John D.

    2016-01-01

    Summary Bacillus subtilis provides a model for investigation of the bacterial cell envelope, the first line of defense against environmental threats. Extracytoplasmic function (ECF) sigma factors activate genes that confer resistance to agents that threaten the integrity of the envelope. Although their individual regulons overlap, σW is most closely associated with membrane-active agents, σX with cationic antimicrobial peptide resistance, and σV with resistance to lysozyme. Here, I highlight the role of the σM regulon, which is strongly induced by conditions that impair peptidoglycan synthesis and includes the core pathways of envelope synthesis and cell division, as well as stress-inducible alternative enzymes. Studies of these cell envelope stress responses provide insights into how bacteria acclimate to the presence of antibiotics. PMID:26901131

  6. Bacillus subtilis extracytoplasmic function (ECF) sigma factors and defense of the cell envelope.

    PubMed

    Helmann, John D

    2016-04-01

    Bacillus subtilis provides a model for investigation of the bacterial cell envelope, the first line of defense against environmental threats. Extracytoplasmic function (ECF) sigma factors activate genes that confer resistance to agents that threaten the integrity of the envelope. Although their individual regulons overlap, σ(W) is most closely associated with membrane-active agents, σ(X) with cationic antimicrobial peptide resistance, and σ(V) with resistance to lysozyme. Here, I highlight the role of the σ(M) regulon, which is strongly induced by conditions that impair peptidoglycan synthesis and includes the core pathways of envelope synthesis and cell division, as well as stress-inducible alternative enzymes. Studies of these cell envelope stress responses provide insights into how bacteria acclimate to the presence of antibiotics.

  7. Role of the Porphyromonas gingivalis ECF sigma factor, SigH

    PubMed Central

    Yanamandra, Sai S.; Sarrafee, Sara S.; Anaya-Bergman, Cecilia; Jones, Kevin; Lewis, Janina P.

    2012-01-01

    Little is known about the regulatory mechanisms that allow Porphyromonas gingivalis to survive in the oral cavity. Here we characterize the sigma factor SigH, one of six extracytoplasmic (ECF) sigma (σ) factors encoded in the P. gingivalis genome. Our results indicate that sigH expression is upregulated by exposure to molecular oxygen, suggesting that sigH plays a role in adaptation of P. gingivalis to oxygen. Furthermore, several genes involved in oxidative stress protection, such as sod, trx, tpx, ftn, feoB2 and the hemin uptake hmu locus, are downregulated in mutant deficient in SigH designated as V2948. ECF σ consensus sequences were identified upstream of the transcriptional start sites of these genes, consistent with the SigH-dependent regulation of these genes. Growth of V2948 was inhibited in the presence of 6% oxygen when compared to the wild-type W83 strain, while in anaerobic conditions both strains were able to grow. In addition, reduced growth of V2948 was observed in the presence of peroxide and thiol-oxidizing reagent, diamide when compared to the W83 strain. The SigH-deficient strain V2948 also exhibited reduced hemin uptake, consistent with the observed reduced expression of genes involved in hemin uptake. Finally, survival of V2948 was reduced in the presence of host cells compared to the wild-type W83 strain. Collectively, our studies demonstrate that SigH is a positive regulator of gene expression required for survival of the bacterium in the presence of oxygen and oxidative stress, hemin uptake, and virulence. PMID:22520389

  8. 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...

  9. A Novel Role for an ECF Sigma Factor in Fatty Acid Biosynthesis and Membrane Fluidity in Pseudomonas aeruginosa

    PubMed Central

    Boechat, Ana Laura; Kaihami, Gilberto Hideo; Politi, Mario José; Lépine, François; Baldini, Regina L.

    2013-01-01

    Extracytoplasmic function (ECF) sigma factors are members of cell-surface signaling systems, abundant in the opportunistic pathogen Pseudomonas aeruginosa. Twenty genes coding for ECF sigma factors are present in P. aeruginosa sequenced genomes, most of them being part of TonB systems related to iron uptake. In this work, poorly characterized sigma factors were overexpressed in strain PA14, in an attempt to understand their role in the bacterium´s physiology. Cultures overexpressing SigX displayed a biphasic growth curve, reaching stationary phase earlier than the control strain, followed by subsequent growth resumption. During the first stationary phase, most cells swell and die, but the remaining cells return to the wild type morphology and proceed to a second exponential growth. This is not due to compensatory mutations, since cells recovered from late time points and diluted into fresh medium repeated this behavior. Swollen cells have a more fluid membrane and contain higher amounts of shorter chain fatty acids. A proteomic analysis was performed to identify differentially expressed proteins due to overexpression of sigX, revealing the induction of several fatty acid synthesis (FAS) enzymes. Using qRT-PCR, we showed that at least one isoform from each of the FAS pathway enzymes were upregulated at the mRNA level in the SigX overexpressing strain thus pointing to a role for this ECF sigma factor in the FAS regulation in P. aeruginosa. PMID:24386415

  10. hrpL activates Erwinia amylovora hrp gene transcription and is a member of the ECF subfamily of sigma factors.

    PubMed Central

    Wei, Z M; Beer, S V

    1995-01-01

    hrpL of Erwinia amylovora Ea321 encodes a 21.7-kDa regulatory protein, similar to members of the ECF (extra cytoplasmic functions) subfamily of eubacterial RNA polymerase sigma factors. hrpL is a single-gene operon in complementation group VI of the E. amylovora hrp gene cluster. Its product is required by Ea321 to elicit the hypersensitive response (HR) and to cause disease. HrpL controls the expression of five independent hrp loci, including hrpN, which encodes harpin, a proteinaceous elicitor of the HR. hrpL is environmentally regulated, and its expression is affected by hrpS, another regulatory gene of the hrp gene cluster of E. amylovora. pCPP1078, a multicopy plasmid carrying hrpL, is able to restore HR-eliciting ability to hrpS mutants. A conserved motif was identified upstream of the hrpI and hrpN operons, which are transcriptionally regulated by hrpL. This conserved motif shares a high degree of similarity with other biochemically defined or putative ECF-dependent promoter sequences, including sequences upstream of Streptomyces coelicolor dagA P2, Pseudomonas aeruginosa algD, Pseudomonas syringae pv. syringae 61 hrpZ, and P. syringae pv. tomato avrD. In spite of the similarity between the hrpL genes of E. amylovora and P. syringae 61, no functional cross-complementation was observed. PMID:7592386

  11. 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

  12. 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 ...

  13. Influence of a Putative ECF Sigma Factor on Expression of the Major Outer Membrane Protein, OprF, in Pseudomonas aeruginosa and Pseudomonas fluorescens

    PubMed Central

    Brinkman, Fiona S. L.; Schoofs, Geert; Hancock, Robert E. W.; De Mot, René

    1999-01-01

    The gene encoding OprF, a major outer membrane protein in Pseudomonas species (formerly known as type 1 pseudomonads), was thought to be constitutively transcribed from a single sigma 70 promoter immediately upstream of the gene. We now report the identification of a novel putative ECF (extracytoplasmic function) sigma factor gene, sigX, located immediately upstream of oprF in both Pseudomonas aeruginosa PAO1 and Pseudomonas fluorescens OE 28.3 and show that disruption of this gene significantly reduces OprF expression. In P. aeruginosa, Northern analysis demonstrated that this reduction was a result of an effect on transcription of monocistronic oprF combined with a polar effect due to termination of a transcript containing sigX and oprF. Comparison of sigX-disrupted and wild-type cell transcripts by primer extension indicated that monocistronic transcription of oprF occurs from two overlapping promoters, one that is SigX-dependent and resembles ECF sigma factor promoters in its minus-35 region and another promoter that is independent of SigX and is analogous to the sigma 70-type promoter previously reported. Complementation of the P. aeruginosa sigX-disrupted mutant with plasmid-encoded OprF did not resolve the phenotypes associated with this mutant, which included a markedly reduced logarithmic-phase growth rate in rich medium (compared to that in minimal medium), further reduction of the growth rate in a low-osmolarity environment, secretion of an unidentified pigment, and increased sensitivity to the antibiotic imipenem. This indicates that SigX is involved in the regulation of other genes in P. aeruginosa. Disruption of the sigX gene in P. fluorescens also had an effect on the logarithmic-phase growth rate in rich medium. A conserved sigX gene was also identified in a Pseudomonas syringae isolate and six P. aeruginosa clinical isolates. Collectively, these data indicate that an ECF sigma factor plays a role in the regulation and expression of OprF and also

  14. A two-component system, an anti-sigma factor and two paralogous ECF sigma factors are involved in the control of general stress response in Caulobacter crescentus.

    PubMed

    Lourenço, Rogério F; Kohler, Christian; Gomes, Suely L

    2011-06-01

    The extracytoplasmic function sigma factor σ(T) is the master regulator of general stress response in Caulobacter crescentus and controls the expression of its paralogue σ(U). In this work we showed that PhyR and NepR act, respectively, as positive and negative regulators of σ(T) expression and function. Biochemical data also demonstrated that NepR directly binds σ(T) and the phosphorylated form of PhyR. We also described the essential role of the histidine kinase gene CC3474, here denominated phyK, for expression of σ(T)-dependent genes and for resistance to stress conditions. Additionally, in vivo evidence of PhyK-dependent phosphorylation of PhyR is presented. This study also identified a conserved cysteine residue (C95) located in the periplasmic portion of PhyK that is crucial for the function of the protein. Furthermore, we showed that PhyK, PhyR and σ(T) regulate the same set of genes and that σ(T) apparently directly controls most of its regulon. In contrast, σ(U) seems to have a very modest contribution to the expression of a subset of σ(T)-dependent genes. In conclusion, this report describes the molecular mechanism involved in the control of general stress response in C. crescentus.

  15. Glucose Induces ECF Sigma Factor Genes, sigX and sigM, Independent of Cognate Anti-sigma Factors through Acetylation of CshA in Bacillus subtilis

    PubMed Central

    Ogura, Mitsuo; Asai, Kei

    2016-01-01

    Extracytoplasmic function (ECF) σ factors have roles related to cell envelope and/or cell membrane functions, in addition to other cellular functions. Without cell-surface stresses, ECF σ factors are sequestered by the cognate anti-σ factor, leading to inactivation and the resultant repression of regulons due to the inhibition of transcription of their own genes. Bacillus subtilis has seven ECF σ factors including σX and σM that transcribe their own structural genes. Here, we report that glucose addition to the medium induced sigX and sigM transcription independent of their anti-σ factors. This induction was dependent on an intracellular acetyl-CoA pool. Transposon mutagenesis searching for the mutants showing no induction of sigX and sigM revealed that the cshA gene encoding DEAD-box RNA helicase is required for gene induction. Global analysis of the acetylome in B. subtilis showed CshA has two acetylated lysine residues. We found that in a cshA mutant with acetylation-abolishing K to R exchange mutations, glucose induction of sigX and sigM was abolished and that glucose addition stimulated acetylation of CshA in the wild type strain. Thus, we present a model wherein glucose addition results in a larger acetyl-CoA pool, probably leading to increased levels of acetylated CshA. CshA is known to associate with RNA polymerase (RNAP), and thus RNAP with acetylated CshA could stimulate the autoregulation of sigX and sigM. This is a unique model showing a functional link between nutritional signals and the basal transcription machinery. PMID:27965645

  16. Glucose Induces ECF Sigma Factor Genes, sigX and sigM, Independent of Cognate Anti-sigma Factors through Acetylation of CshA in Bacillus subtilis.

    PubMed

    Ogura, Mitsuo; Asai, Kei

    2016-01-01

    Extracytoplasmic function (ECF) σ factors have roles related to cell envelope and/or cell membrane functions, in addition to other cellular functions. Without cell-surface stresses, ECF σ factors are sequestered by the cognate anti-σ factor, leading to inactivation and the resultant repression of regulons due to the inhibition of transcription of their own genes. Bacillus subtilis has seven ECF σ factors including σ(X) and σ(M) that transcribe their own structural genes. Here, we report that glucose addition to the medium induced sigX and sigM transcription independent of their anti-σ factors. This induction was dependent on an intracellular acetyl-CoA pool. Transposon mutagenesis searching for the mutants showing no induction of sigX and sigM revealed that the cshA gene encoding DEAD-box RNA helicase is required for gene induction. Global analysis of the acetylome in B. subtilis showed CshA has two acetylated lysine residues. We found that in a cshA mutant with acetylation-abolishing K to R exchange mutations, glucose induction of sigX and sigM was abolished and that glucose addition stimulated acetylation of CshA in the wild type strain. Thus, we present a model wherein glucose addition results in a larger acetyl-CoA pool, probably leading to increased levels of acetylated CshA. CshA is known to associate with RNA polymerase (RNAP), and thus RNAP with acetylated CshA could stimulate the autoregulation of sigX and sigM. This is a unique model showing a functional link between nutritional signals and the basal transcription machinery.

  17. 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

  18. Identification of Disulphide Stress-responsive Extracytoplasmic Function Sigma Factors in Rothia mucilaginosa

    DTIC Science & Technology

    2013-01-01

    Mycobacterium tuberculosis extracytoplasmic-function sigma factor SigL regulates polyketide synthases and secreted or membrane proteins and is required for...analysis on the available database of R. mucilaginosa ATCC 25296 (a type strain for R. mucilaginosa) revealed that ATCC 25296 has three sigma factors: one ...primary sigma factor and two ECF sigma factors, one of which was highly homologous to that of DY-18. ECF sigma factors play an important role in the

  19. 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...

  20. σ(ECF) factors of gram-positive bacteria: a focus on Bacillus subtilis and the CMNR group.

    PubMed

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

    2014-07-01

    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 σ(ECF) 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.

  1. An extra-cytoplasmic function sigma factor and anti-sigma factor control carotenoid biosynthesis in Azospirillum brasilense.

    PubMed

    Thirunavukkarasu, Nagarajan; Mishra, Mukti Nath; Spaepen, Stijn; Vanderleyden, Jos; Gross, Carol A; Tripathi, Anil K

    2008-07-01

    Strains Sp7 and Cd of Azospirillum brasilense, a plant growth-promoting rhizobacterium, differ in synthesis of carotenoids. While colonies of strain Sp7 have a white-cream colour on plates, colonies of strain Cd are orange-pink coloured because of the synthesis of carotenoids. Screening of a mini-Tn5 mutant library of A. brasilense Sp7 revealed two orange-pink-coloured mutants that produced carotenoids. Cloning and sequencing of the Tn5 flanking region in both the carotenoid-producing mutants of Sp7 revealed insertion of Tn5 in an ORF encoding anti-sigma factor, a ChrR-like protein. The upstream region of the Tn5-mutated ORF contained another ORF that encoded an extra-cytoplasmic function (ECF)-class sigma factor (sigma(E), RpoE). When the nucleotide sequences of the corresponding ORFs from the carotenoid-producing strain Cd were analysed, the sequence of the Cd sigma(E) was identical to that of the carotenoid non-producing strain Sp7, but the Cd anti-sigma(E) ORF had a deletion that caused frame shifting and creation of a stop codon. This resulted in the premature termination of the protein, which was about 7 kDa smaller than the Sp7 anti-sigma(E). Cloning of Sp7 anti-sigma(E) in a broad-host-range expression vector and expression in A. brasilense Cd and in the anti-sigma(E) knockout mutant of A. brasilense Sp7 resulted in the inhibition of carotenoid synthesis. Similarly, cloning and overexpression of A. brasilense Sp7 sigma(E) in A. brasilense Sp7 resulted in the production of carotenoids. These observations clearly indicate that carotenoid synthesis in A. brasilense is controlled by sigma(E) with its cognate anti-sigma(E).

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

    DOE PAGES

    Allen, Michael S.; Hurst, Gregory B.; Lu, Tse-Yuan S.; ...

    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

  3. 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.

  4. The Bartonella quintana Extracytoplasmic Function Sigma Factor RpoE Has a Role in Bacterial Adaptation to the Arthropod Vector Environment

    PubMed Central

    Abromaitis, Stephanie

    2013-01-01

    Bartonella quintana is a vector-borne bacterial pathogen that causes fatal disease in humans. During the infectious cycle, B. quintana transitions from the hemin-restricted human bloodstream to the hemin-rich body louse vector. Because extracytoplasmic function (ECF) sigma factors often regulate adaptation to environmental changes, we hypothesized that a previously unstudied B. quintana ECF sigma factor, RpoE, is involved in the transition from the human host to the body louse vector. The genomic context of B. quintana rpoE identified it as a member of the ECF15 family of sigma factors found only in alphaproteobacteria. ECF15 sigma factors are believed to be the master regulators of the general stress response in alphaproteobacteria. In this study, we examined the B. quintana RpoE response to two stressors that are encountered in the body louse vector environment, a decreased temperature and an increased hemin concentration. We determined that the expression of rpoE is significantly upregulated at the body louse (28°C) versus the human host (37°C) temperature. rpoE expression also was upregulated when B. quintana was exposed to high hemin concentrations. In vitro and in vivo analyses demonstrated that RpoE function is regulated by a mechanism involving the anti-sigma factor NepR and the response regulator PhyR. The ΔrpoE ΔnepR mutant strain of B. quintana established that RpoE-mediated transcription is important in mediating the tolerance of B. quintana to high hemin concentrations. We present the first analysis of an ECF15 sigma factor in a vector-borne human pathogen and conclude that RpoE has a role in the adaptation of B. quintana to the hemin-rich arthropod vector environment. PMID:23564167

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

    PubMed

    Paget, Mark S

    2015-06-26

    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.

  6. 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

  7. 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.

  8. Regulation of toxin and bacteriocin synthesis in Clostridium species by a new subgroup of RNA polymerase sigma-factors.

    PubMed

    Dupuy, Bruno; Matamouros, Susana

    2006-04-01

    Many Clostridium species are pathogenic for humans and animals, and most of the resulting diseases, such as tetanus, botulism, gas gangrene and pseudomembranous colitis, are due to the production of potent extracellular toxins. The biochemical mechanisms of action of Clostridium toxins have been extensively studied in the past ten years. However, detailed information about the regulation of toxin gene expression has only recently emerged. TcdR, BotR, TetR and UviA are now known to be related alternative RNA polymerase sigma factors that drive transcription of toxin A and toxin B genes in C. difficile, the neurotoxin genes in C. botulinum and C. tetani, and a bacteriocin gene in C. perfringens. Although the Clostridium sigma factors have some similarity to members of the ECF sigma factor group, they differ sufficiently in structure and function so that they have been assigned to a new group within the sigma(70)-family.

  9. An extracytoplasmic function sigma factor acts as a general stress response regulator in Sinorhizobium meliloti.

    PubMed

    Sauviac, Laurent; Philippe, Heinui; Phok, Kounthéa; Bruand, Claude

    2007-06-01

    Sinorhizobium meliloti genes transcriptionally up-regulated after heat stress, as well as upon entry into stationary phase, were identified by microarray analyses. Sixty stress response genes were thus found to be up-regulated under both conditions. One of them, rpoE2 (smc01506), encodes a putative extracytoplasmic function (ECF) sigma factor. We showed that this sigma factor controls its own transcription and is activated by various stress conditions, including heat and salt, as well as entry into stationary phase after either carbon or nitrogen starvation. We also present evidence that the product of the gene cotranscribed with rpoE2 negatively regulates RpoE2 activity, and we therefore propose that it plays the function of anti-sigma factor. By combining transcriptomic, bioinformatic, and quantitative reverse transcription-PCR analyses, we identified 44 RpoE2-controlled genes and predicted the number of RpoE2 targets to be higher. Strikingly, more than one-third of the 60 stress response genes identified in this study are RpoE2 targets. Interestingly, two genes encoding proteins with known functions in stress responses, namely, katC and rpoH2, as well as a second ECF-encoding gene, rpoE5, were found to be RpoE2 regulated. Altogether, these data suggest that RpoE2 is a major global regulator of the general stress response in S. meliloti. Despite these observations, and although this sigma factor is well conserved among alphaproteobacteria, no in vitro nor in planta phenotypic difference from the wild-type strain could be detected for rpoE2 mutants. This therefore suggests that other important actors in the general stress response have still to be identified in S. meliloti.

  10. 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

  11. 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...

  12. 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

  13. A model for sigma factor competition in bacterial cells.

    PubMed

    Mauri, Marco; Klumpp, Stefan

    2014-10-01

    Sigma factors control global switches of the genetic expression program in bacteria. Different sigma factors compete for binding to a limited pool of RNA polymerase (RNAP) core enzymes, providing a mechanism for cross-talk between genes or gene classes via the sharing of expression machinery. To analyze the contribution of sigma factor competition to global changes in gene expression, we develop a theoretical model that describes binding between sigma factors and core RNAP, transcription, non-specific binding to DNA and the modulation of the availability of the molecular components. The model is validated by comparison with in vitro competition experiments, with which excellent agreement is found. Transcription is affected via the modulation of the concentrations of the different types of holoenzymes, so saturated promoters are only weakly affected by sigma factor competition. However, in case of overlapping promoters or promoters recognized by two types of sigma factors, we find that even saturated promoters are strongly affected. Active transcription effectively lowers the affinity between the sigma factor driving it and the core RNAP, resulting in complex cross-talk effects. Sigma factor competition is not strongly affected by non-specific binding of core RNAPs, sigma factors and holoenzymes to DNA. Finally, we analyze the role of increased core RNAP availability upon the shut-down of ribosomal RNA transcription during the stringent response. We find that passive up-regulation of alternative sigma-dependent transcription is not only possible, but also displays hypersensitivity based on the sigma factor competition. Our theoretical analysis thus provides support for a significant role of passive control during that global switch of the gene expression program.

  14. A Model for Sigma Factor Competition in Bacterial Cells

    PubMed Central

    Mauri, Marco; Klumpp, Stefan

    2014-01-01

    Sigma factors control global switches of the genetic expression program in bacteria. Different sigma factors compete for binding to a limited pool of RNA polymerase (RNAP) core enzymes, providing a mechanism for cross-talk between genes or gene classes via the sharing of expression machinery. To analyze the contribution of sigma factor competition to global changes in gene expression, we develop a theoretical model that describes binding between sigma factors and core RNAP, transcription, non-specific binding to DNA and the modulation of the availability of the molecular components. The model is validated by comparison with in vitro competition experiments, with which excellent agreement is found. Transcription is affected via the modulation of the concentrations of the different types of holoenzymes, so saturated promoters are only weakly affected by sigma factor competition. However, in case of overlapping promoters or promoters recognized by two types of sigma factors, we find that even saturated promoters are strongly affected. Active transcription effectively lowers the affinity between the sigma factor driving it and the core RNAP, resulting in complex cross-talk effects. Sigma factor competition is not strongly affected by non-specific binding of core RNAPs, sigma factors and holoenzymes to DNA. Finally, we analyze the role of increased core RNAP availability upon the shut-down of ribosomal RNA transcription during the stringent response. We find that passive up-regulation of alternative sigma-dependent transcription is not only possible, but also displays hypersensitivity based on the sigma factor competition. Our theoretical analysis thus provides support for a significant role of passive control during that global switch of the gene expression program. PMID:25299042

  15. Dual control of Sinorhizobium meliloti RpoE2 sigma factor activity by two PhyR-type two-component response regulators.

    PubMed

    Bastiat, Bénédicte; Sauviac, Laurent; Bruand, Claude

    2010-04-01

    RpoE2 is an extracytoplasmic function (ECF) sigma factor involved in the general stress response of Sinorhizobium meliloti, the nitrogen-fixing symbiont of the legume plant alfalfa. RpoE2 orthologues are widely found among alphaproteobacteria, where they play various roles in stress resistance and/or host colonization. In this paper, we report a genetic and biochemical investigation of the mechanisms of signal transduction leading to S. meliloti RpoE2 activation in response to stress. We showed that RpoE2 activity is negatively controlled by two paralogous anti-sigma factors, RsiA1 (SMc01505) and RsiA2 (SMc04884), and that RpoE2 activation by stress requires two redundant paralogous PhyR-type response regulators, RsiB1 (SMc01504) and RsiB2 (SMc00794). RsiB1 and RsiB2 do not act at the level of rpoE2 transcription but instead interact with the anti-sigma factors, and we therefore propose that they act as anti-anti-sigma factors to relieve RpoE2 inhibition in response to stress. This model closely resembles a recently proposed model of activation of RpoE2-like sigma factors in Methylobacterium extorquens and Bradyrhizobium japonicum, but the existence of two pairs of anti- and anti-anti-sigma factors in S. meliloti adds an unexpected level of complexity, which may allow the regulatory system to integrate multiple stimuli.

  16. The ornibactin biosynthesis and transport genes of Burkholderia cenocepacia are regulated by an extracytoplasmic function sigma factor which is a part of the Fur regulon.

    PubMed

    Agnoli, Kirsty; Lowe, Carolyn A; Farmer, Kate L; Husnain, Seyyed I; Thomas, Mark S

    2006-05-01

    Burkholderia cenocepacia mutants that fail to produce the siderophore ornibactin were obtained following mutagenesis with mini-Tn5Tp. These mutants were shown to be growth restricted under conditions of iron depletion. In eight of the mutants, the transposon had integrated into one of two genes, orbI and orbJ, encoding nonribosomal peptide synthetases. In the other mutant, the transposon had inserted into an open reading frame, orbS, located upstream from orbI. The polypeptide product of orbS exhibits a high degree of similarity to the Pseudomonas aeruginosa extracytoplasmic function (ECF) sigma factor PvdS but possesses an N-terminal extension of approximately 29 amino acids that is not present in PvdS. Three predicted OrbS-dependent promoters were identified within the ornibactin gene cluster, based on their similarity to PvdS-dependent promoters. The iron-regulated activity of these promoters was shown to require OrbS. Transcription of the orbS gene was found to be under the control of an iron-regulated sigma(70)-dependent promoter. This promoter, but not the OrbS-dependent promoters, was shown to be a target for repression by the global regulator Fur. Our results demonstrate that production of ornibactin by B. cenocepacia in response to iron starvation requires transcription of an operon that is dependent on the Fur-regulated ECF sigma factor gene orbS. A mechanism is also proposed for the biosynthesis of ornibactin.

  17. Sinorhizobium meliloti sigma factors RpoE1 and RpoE4 are activated in stationary phase in response to sulfite.

    PubMed

    Bastiat, Bénédicte; Sauviac, Laurent; Picheraux, Carole; Rossignol, Michel; Bruand, Claude

    2012-01-01

    Rhizobia are soil bacteria able to establish a nitrogen-fixing symbiosis with legume plants. Both in soil and in planta, rhizobia spend non-growing periods resembling the stationary phase of in vitro-cultured bacteria. The primary objective of this work was to better characterize gene regulation in this biologically relevant growth stage in Sinorhizobium meliloti. By a tap-tag/mass spectrometry approach, we identified five sigma factors co-purifying with the RNA polymerase in stationary phase: the general stress response regulator RpoE2, the heat shock sigma factor RpoH2, and three extra-cytoplasmic function sigma factors (RpoE1, RpoE3 and RpoE4) belonging to the poorly characterized ECF26 subgroup. We then showed that RpoE1 and RpoE4 i) are activated upon metabolism of sulfite-generating compounds (thiosulfate and taurine), ii) display overlapping regulatory activities, iii) govern a dedicated sulfite response by controlling expression of the sulfite dehydrogenase SorT, iv) are activated in stationary phase, likely as a result of endogenous sulfite generation during bacterial growth. We showed that SorT is required for optimal growth of S. meliloti in the presence of sulfite, suggesting that the response governed by RpoE1 and RpoE4 may be advantageous for bacteria in stationary phase either by providing a sulfite detoxification function or by contributing to energy production through sulfite respiration. This paper therefore reports the first characterization of ECF26 sigma factors, the first description of sigma factors involved in control of sulphur metabolism, and the first indication that endogenous sulfite may act as a signal for regulation of gene expression upon entry of bacteria in stationary phase.

  18. An unusual primary sigma factor in the Bacteroidetes phylum.

    PubMed

    Vingadassalom, Didier; Kolb, Annie; Mayer, Claudine; Rybkine, Tania; Collatz, Ekkehard; Podglajen, Isabelle

    2005-05-01

    The presence of housekeeping gene promoters with a unique consensus sequence in Bacteroides fragilis, previously described by Bayley et al. (2000, FEMS Microbiol Lett 193: 149-154), suggested the existence of a particular primary sigma factor. The single rpoD-like gene observed in the B. fragilis genome, and similarly in those of other members of the Bacteroidetes phylum, was found to be essential. It encodes a protein, sigma(ABfr), of only 32.7 kDa that is produced with equal abundance during all phases of growth and was concluded to be the primary sigma factor. sigma(ABfr) and its orthologues in the Bacteroidetes are unusual primary sigma factors in that they lack region 1.1, have a unique signature made up of 29 strictly identical amino acids and are the only RpoD factors that cluster with the RpoS factors. Although binding to the Escherichia coli core RNA polymerase, sigma(ABfr) does not support transcription initiation from any promoter when it is part of the heterologous holoenzyme, while in the reconstituted homologous holoenzyme it does so only from typical B. fragilis, including rrs, promoters but not from the lacUV5 or RNA I promoters.

  19. Alternative sigma factor RpoN and its modulation protein YhbH are indispensable for Erwinia amylovora virulence.

    PubMed

    Ancona, Veronica; Li, Wenting; Zhao, Youfu

    2014-01-01

    In Erwinia amylovora, ECF (extracytoplasmic functions) alternative sigma factor HrpL regulates the transcription of hrp (hypersensitive response and pathogenicity)-type III secretion system (T3SS) genes by binding to a consensus sequence known as the hrp box in hrp gene promoters. In turn, the expression of hrpL has been proposed to be positively controlled by alternative sigma factor 54 (σ(54)) (RpoN) and HrpS, a member of the σ(54) enhancer-binding proteins (EBPs). However, the function of RpoN has not been characterized genetically in E. amylovora. In this study, we investigated the role of RpoN, a nitrogen limitation sigma factor, and its modulation protein YhbH, a novel ribosome-associated protein, in E. amylovora virulence. Our results showed that mutations in hrpS, hrpL, rpoN and yhbH, but not yfiA and rmf3, resulted in a nonpathogenic phenotype on immature pear fruits and apple shoots. Consistently, the expression of T3SS genes, including hrpL, dspE, hrpN and hrpA, was barely detected in hrpS, hrpL, rpoN and yhbH mutants. These mutants were also not capable of eliciting a hypersensitive response (HR) on tobacco; however, the overexpression of hrpL using an inducible promoter rescued the HR-eliciting abilities of these mutants. These results suggest that a sigma factor cascade exists in the regulatory networks of E. amylovora and regulates important virulence factors. On the basis of this study and previously reported data, a model is proposed for the regulation of T3SS in E. amylovora.

  20. 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

  1. 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.

  2. 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.

  3. Dual Control of Sinorhizobium meliloti RpoE2 Sigma Factor Activity by Two PhyR-Type Two-Component Response Regulators▿ †

    PubMed Central

    Bastiat, Bénédicte; Sauviac, Laurent; Bruand, Claude

    2010-01-01

    RpoE2 is an extracytoplasmic function (ECF) sigma factor involved in the general stress response of Sinorhizobium meliloti, the nitrogen-fixing symbiont of the legume plant alfalfa. RpoE2 orthologues are widely found among alphaproteobacteria, where they play various roles in stress resistance and/or host colonization. In this paper, we report a genetic and biochemical investigation of the mechanisms of signal transduction leading to S. meliloti RpoE2 activation in response to stress. We showed that RpoE2 activity is negatively controlled by two paralogous anti-sigma factors, RsiA1 (SMc01505) and RsiA2 (SMc04884), and that RpoE2 activation by stress requires two redundant paralogous PhyR-type response regulators, RsiB1 (SMc01504) and RsiB2 (SMc00794). RsiB1 and RsiB2 do not act at the level of rpoE2 transcription but instead interact with the anti-sigma factors, and we therefore propose that they act as anti-anti-sigma factors to relieve RpoE2 inhibition in response to stress. This model closely resembles a recently proposed model of activation of RpoE2-like sigma factors in Methylobacterium extorquens and Bradyrhizobium japonicum, but the existence of two pairs of anti- and anti-anti-sigma factors in S. meliloti adds an unexpected level of complexity, which may allow the regulatory system to integrate multiple stimuli. PMID:20154128

  4. Shifts from glucose to certain secondary carbon-sources result in activation of the extracytoplasmic function sigma factor sigmaE in Salmonella enterica serovar Typhimurium.

    PubMed

    Kenyon, William J; Thomas, Sheena M; Johnson, Erin; Pallen, Mark J; Spector, Michael P

    2005-07-01

    Salmonella enterica serovar Typhimurium (S. Typhimurium) elicits the starvation-stress response (SSR) due to starvation for an essential nutrient, e.g. a carbon/energy source (C-source). As part of the SSR, the alternative sigma factor sigma(E) is activated and induced. The authors suspect that this activation is, in part, triggered by changes in the S. Typhimurium cell envelope occurring during the adaptation from growth to carbon/energy starvation (C-starvation), and resulting in an increased need for sigma(E)-regulated factors involved in the proper folding and assembly of newly synthesized proteins destined for this extracytoplasmic compartment. This led to the hypothesis that a sigma(E) activation signal might arise during C-source shifts that cause the induction of proteins localized to the extracytoplasmic compartment, i.e. the outer membrane or periplasm, of the cell. To test this hypothesis, cultures were grown in minimal medium containing enough glucose to reach mid-exponential-phase, plus a non-limiting amount of a secondary 'less-preferred' but utilizable carbon/energy source. The sigma(E) activity was then monitored using plasmids carrying rpoEP1- and rpoEP2-lacZ transcriptional fusions, which exhibit sigma(E)-independent and -dependent lacZ expression, respectively. The secondary C-sources maltose, succinate and citrate, which have extracytoplasmic components involved in their utilization (e.g. LamB), resulted in a discernible diauxic lag period and a sustained increase in sigma(E) activity. Growth transition from glucose to other utilizable phosphotransferase (PTS) and non-PTS C-sources, such as trehalose, mannose, mannitol, fructose, glycerol, d-galactose or l-arabinose, did not cause a discernible diauxic lag period or a sustained increase in sigma(E) activity. Interestingly, a shift from glucose to melibiose, which does not use an extracytoplasmic-localized protein for uptake, did cause an observable diauxic lag period but did not result in a

  5. Role of Autoregulation and Relative Synthesis of Operon Partners in Alternative Sigma Factor Networks

    PubMed Central

    2016-01-01

    Despite the central role of alternative sigma factors in bacterial stress response and virulence their regulation remains incompletely understood. Here we investigate one of the best-studied examples of alternative sigma factors: the σB network that controls the general stress response of Bacillus subtilis to uncover widely relevant general design principles that describe the structure-function relationship of alternative sigma factor regulatory networks. We show that the relative stoichiometry of the synthesis rates of σB, its anti-sigma factor RsbW and the anti-anti-sigma factor RsbV plays a critical role in shaping the network behavior by forcing the σB network to function as an ultrasensitive negative feedback loop. We further demonstrate how this negative feedback regulation insulates alternative sigma factor activity from competition with the housekeeping sigma factor for RNA polymerase and allows multiple stress sigma factors to function simultaneously with little competitive interference. PMID:27977677

  6. 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

  7. 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

    2016-03-31

    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.

  8. Negative regulation of germination-arrest factor production in Pseudomonas fluorescens WH6 by a putative extracytoplasmic function sigma factor.

    PubMed

    Okrent, Rachel A; Halgren, Anne B; Azevedo, Mark D; Chang, Jeff H; Mills, Dallice I; Maselko, Maciej; Armstrong, Donald J; Banowetz, Gary M; Trippe, Kristin M

    2014-11-01

    Pseudomonas fluorescens WH6 secretes a germination-arrest factor (GAF) that we have identified previously as 4-formylaminooxyvinylglycine. GAF irreversibly inhibits germination of the seeds of numerous grassy weeds and selectively inhibits growth of the bacterial plant pathogen Erwinia amylovora. WH6-3, a mutant that has lost the ability to produce GAF, contains a Tn5 insertion in prtR, a gene that has been described previously in some strains of P. fluorescens as encoding a transmembrane regulator. As in these other pseudomonads, in WH6, prtR occurs immediately downstream of prtI, which encodes a protein homologous to extracytoplasmic function (ECF) sigma factors. These two genes have been proposed to function as a dicistronic operon. In this study, we demonstrated that deletion of prtI in WT WH6 had no effect on GAF production. However, deletion of prtI in the WH6-3 mutant overcame the effects of the Tn5 insertion in prtR and restored GAF production in the resulting double mutant. Complementation of the double prtIR mutant with prtI suppressed GAF production. This overall pattern of prtIR regulation was also observed for the activity of an AprX protease. Furthermore, reverse transcription quantitative real-time PCR analysis demonstrated that alterations in GAF production were mirrored by changes in the transcription of two putative GAF biosynthetic genes. Thus, we concluded that PrtI exerted a negative regulatory effect on GAF production, although the mechanism has not yet been determined. In addition, evidence was obtained that the transcription of prtI and prtR in WH6 may be more complex than predicted by existing models.

  9. 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

  10. 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

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

    PubMed

    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.

  12. 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

  13. 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.

  14. The essential activities of the bacterial sigma factor.

    PubMed

    Davis, Maria C; Kesthely, Christopher A; Franklin, Emily A; MacLellan, Shawn R

    2017-02-01

    Transcription is the first and most heavily regulated step in gene expression. Sigma (σ) factors are general transcription factors that reversibly bind RNA polymerase (RNAP) and mediate transcription of all genes in bacteria. σ Factors play 3 major roles in the RNA synthesis initiation process: they (i) target RNAP holoenzyme to specific promoters, (ii) melt a region of double-stranded promoter DNA and stabilize it as a single-stranded open complex, and (iii) interact with other DNA-binding transcription factors to contribute complexity to gene expression regulation schemes. Recent structural studies have demonstrated that when σ factors bind promoter DNA, they capture 1 or more nucleotides that are flipped out of the helical DNA stack and this stabilizes the promoter open-complex intermediate that is required for the initiation of RNA synthesis. This review describes the structure and function of the σ(70) family of σ proteins and the essential roles they play in the transcription process.

  15. 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

  16. Anti-Sigma Factors in E. coli: Common Regulatory Mechanisms Controlling Sigma Factors Availability

    PubMed Central

    Treviño-Quintanilla, Luis Gerardo; Freyre-González, Julio Augusto; Martínez-Flores, Irma

    2013-01-01

    In bacteria, transcriptional regulation is a key step in cellular gene expression. All bacteria contain a core RNA polymerase that is catalytically competent but requires an additional σ factor for specific promoter recognition and correct transcriptional initiation. The RNAP core is not able to selectively bind to a given σ factor. In contrast, different σ factors have different affinities for the RNAP core. As a consequence, the concentration of alternate σ factors requires strict regulation in order to properly control the delicate interplay among them, which favors the competence for the RNAP core. This control is archived by different σ/anti-σ controlling mechanisms that shape complex regulatory networks and cascades, and enable the response to sudden environmental cues, whose global understanding is a current challenge for systems biology. Although there have been a number of excellent studies on each of these σ/anti-σ post-transcriptional regulatory systems, no comprehensive comparison of these mechanisms in a single model organism has been conducted. Here, we survey all these systems in E. coli dissecting and analyzing their inner workings and highlightin their differences. Then, following an integral approach, we identify their commonalities and outline some of the principles exploited by the cell to effectively and globally reprogram the transcriptional machinery. These principles provide guidelines for developing biological synthetic circuits enabling an efficient and robust response to sudden stimuli. PMID:24396271

  17. Anti-Sigma Factors in E. coli: Common Regulatory Mechanisms Controlling Sigma Factors Availability.

    PubMed

    Treviño-Quintanilla, Luis Gerardo; Freyre-González, Julio Augusto; Martínez-Flores, Irma

    2013-09-01

    In bacteria, transcriptional regulation is a key step in cellular gene expression. All bacteria contain a core RNA polymerase that is catalytically competent but requires an additional σ factor for specific promoter recognition and correct transcriptional initiation. The RNAP core is not able to selectively bind to a given σ factor. In contrast, different σ factors have different affinities for the RNAP core. As a consequence, the concentration of alternate σ factors requires strict regulation in order to properly control the delicate interplay among them, which favors the competence for the RNAP core. This control is archived by different σ/anti-σ controlling mechanisms that shape complex regulatory networks and cascades, and enable the response to sudden environmental cues, whose global understanding is a current challenge for systems biology. Although there have been a number of excellent studies on each of these σ/anti-σ post-transcriptional regulatory systems, no comprehensive comparison of these mechanisms in a single model organism has been conducted. Here, we survey all these systems in E. coli dissecting and analyzing their inner workings and highlightin their differences. Then, following an integral approach, we identify their commonalities and outline some of the principles exploited by the cell to effectively and globally reprogram the transcriptional machinery. These principles provide guidelines for developing biological synthetic circuits enabling an efficient and robust response to sudden stimuli.

  18. 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.

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

    PubMed Central

    Woods, Emily C.; Nawrocki, Kathryn L.; Suárez, Jose M.

    2016-01-01

    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 σV does not induce dlt expression in response to lysozyme, indicating that σV 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 σV-dependent manner and that this pathway impacts virulence in vivo. PMID:27068095

  20. 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.

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

    DOE PAGES

    Dai, Jingcheng; Wei, Hehong; Tian, Chunyuan; ...

    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

  2. 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...

  3. 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...

  4. CorE from Myxococcus xanthus Is a Copper-Dependent RNA Polymerase Sigma Factor

    PubMed Central

    Gómez-Santos, Nuria; Pérez, Juana; Sánchez-Sutil, María Celestina; Moraleda-Muñoz, Aurelio; Muñoz-Dorado, José

    2011-01-01

    The dual toxicity/essentiality of copper forces cells to maintain a tightly regulated homeostasis for this metal in all living organisms, from bacteria to humans. Consequently, many genes have previously been reported to participate in copper detoxification in bacteria. Myxococcus xanthus, a prokaryote, encodes many proteins involved in copper homeostasis that are differentially regulated by this metal. A σ factor of the ECF (extracytoplasmic function) family, CorE, has been found to regulate the expression of the multicopper oxidase cuoB, the P1B-type ATPases copA and copB, and a gene encoding a protein with a heavy-metal-associated domain. Characterization of CorE has revealed that it requires copper to bind DNA in vitro. Genes regulated by CorE exhibit a characteristic expression profile, with a peak at 2 h after copper addition. Expression rapidly decreases thereafter to basal levels, although the metal is still present in the medium, indicating that the activity of CorE is modulated by a process of activation and inactivation. The use of monovalent and divalent metals to mimic Cu(I) and Cu(II), respectively, and of additives that favor the formation of the two redox states of this metal, has revealed that CorE is activated by Cu(II) and inactivated by Cu(I). The activation/inactivation properties of CorE reside in a Cys-rich domain located at the C terminus of the protein. Point mutations at these residues have allowed the identification of several Cys involved in the activation and inactivation of CorE. Based on these data, along with comparative genomic studies, a new group of ECF σ factors is proposed, which not only clearly differs mechanistically from the other σ factors so far characterized, but also from other metal regulators. PMID:21655090

  5. 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.

  6. 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.

  7. Regulation of toxin and bacteriocin gene expression in Clostridium by interchangeable RNA polymerase sigma factors.

    PubMed

    Dupuy, Bruno; Raffestin, Stéphanie; Matamouros, Susana; Mani, Nagraj; Popoff, Michel R; Sonenshein, Abraham L

    2006-05-01

    The production of major extracellular toxins by pathogenic strains of Clostridium botulinum, Clostridium tetani and Clostridium difficile, and a bacteriocin by Clostridium perfringens is dependent on a related group of RNA polymerase sigma-factors. These sigma-factors (BotR, TetR, TcdR and UviA) were shown to be sufficiently similar that they could substitute for one another in in vitro DNA binding and run-off transcription experiments. In cells, however, the sigma-factors fell into two subclasses. BotR and TetR were able to direct transcription of their target genes in a fully reciprocal manner. Similarly, UviA and TcdR were fully interchangeable. Neither BotR nor TetR could substitute for UviA or TcdR, however, and neither UviA nor TcdR could direct transcription of the natural targets of BotR or TetR. The extent of functional interchangeability of the sigma-factors was attributed to the strong conservation of their subregion 4.2 sequences and the conserved -35 sequences of their target promoters, while restrictions on interchangeability were attributed to variations in their subregion 2.4 sequences and the target site -10 sequences. The four sigma-factors have been assigned to group 5 of the sigma(70) family and seem to have arisen from a common ancestral protein that may have co-evolved with the genes whose transcription they direct. A fifth Clostridiumsigma-factor, sigma(Y) of Clostridium acetobutylicum, resembles the TcdR family, but was not functionally interchangeable with members of this family.

  8. {sigma}({chi}{sub c1})/{sigma}({chi}{sub c2}) ratio in the k{sub t}-factorization approach

    SciTech Connect

    Baranov, S. P.

    2011-02-01

    We address the puzzle of {sigma}({chi}{sub c1})/{sigma}({chi}{sub c2}) ratio at the collider and fixed-target experiments. We consider several factors that can affect the predicted ratio of the production rates. In particular, we discuss the effect of {chi}{sub cJ} polarization, the effect of including next-to-leading order contributions, and the effect of probably different {chi}{sub c1} and {chi}{sub c2} wave functions.

  9. 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

  10. 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.

  11. 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.

  12. Sigma Filter

    NASA Technical Reports Server (NTRS)

    Balgovind, R. C.

    1985-01-01

    The GLA Fourth-Order model is needed to smooth the topography. This is to remove the Gibbs phenomenon. The Gibbs phenomenon occurs whenever we truncate a Fourier Series. The Sigma factors were introduced to reduce the Gibbs phenomenon. It is found that the smooth Fourier series is nothing but the original Fourier series with its coefficients multiplied by corresponding sigma factors. This operator can be applied many times to obtain high order sigma filtered field and is easily applicable using FFT. It is found that this filter is beneficial in deriving the topography.

  13. 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

  14. Molecular characterization of a positively photoregulated nuclear gene for a chloroplast RNA polymerase sigma factor in Cyanidium caldarium.

    PubMed Central

    Liu, B; Troxler, R F

    1996-01-01

    We have cloned the gene for a putative chloroplast RNA polymerase sigma factor from the unicellular rhodophyte Cyanidium caldarium. This gene contains an open reading frame encoding a protein of 609 amino acids with domains highly homologous to all four conserved regions found in bacterial and cyanobacterial sigma 70-type subunits. When Southern blots of genomic DNA were hybridized to the "rpoD box" oligonucleotide probe, up to six hybridizing hands were observed. Transcripts of the sigma factor gene were undetectable in RNA from dark-grown cells but were abundant in the poly(A)+ fraction of RNA from illuminated cells. The sigma factor gene was expressed in Escherichia coli, and antibodies against the expressed sigma factor fusion protein cross-reacted with a 55-kDa protein in partially purified chloroplast RNA polymerase. Antibodies directed against a cyanobacterial RNA polymerase sigma factor also cross-reacted with a 55-kDa protein in the same enzyme preparation. Immunoprecipitation experiments showed that this enzyme preparation contains proteins with the same molecular weights as the alpha, beta, beta', and beta" subunits of chloroplast RNA polymerase in higher plants. This study identifies a gene for a plastid RNA polymerase sigma factor and indicates that there may be a family of nuclear-encoded sigma factors that recognize promoters in subsets of plastid genes and regulate differential gene expression at the transcriptional level. Images Fig. 1 Fig. 4 Fig. 6 PMID:8622935

  15. 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 ...

  16. Transcription activation of a UV-inducible Clostridium perfringens bacteriocin gene by a novel sigma factor.

    PubMed

    Dupuy, Bruno; Mani, Nagraj; Katayama, Seiichi; Sonenshein, Abraham L

    2005-02-01

    Expression of the plasmid-encoded Clostridium perfringens gene for bacteriocin BCN5 was shown to depend in vivo and in vitro on the activity of UviA protein. UviA, also plasmid-encoded, proved to be an RNA polymerase sigma factor and was also partly autoregulatory. The uviA gene has two promoters; one provided a UviA-independent, basal level of gene expression while the stronger, UviA-dependent promoter was only utilized after the cell experienced DNA damage. As a result, BCN5 synthesis is induced by treatment with UV light or mitomycin C. UviA is related to a special class of sigma factors found to date only in Clostridium species and responsible for activating transcription of toxin genes in Clostridium difficile, Clostridium tetani, and Clostridium botulinum.

  17. Expression of Heterologous Sigma Factor Expands the Searchable Space for Biofuel Tolerance Mechanisms.

    PubMed

    Tomko, Timothy A; Dunlop, Mary J

    2017-04-03

    Microorganisms can produce hydrocarbons that can serve as replacements or additions to conventional liquid fuels for use in the transportation sector. However, a common problem in the microbial synthesis of biofuels is that these compounds often have toxic effects on the cell. In this study, we focused on mitigating the toxicity of the biojet fuel precursor pinene on Escherichia coli. We used genomic DNA from Pseudomonas putida KT2440, which has innate solvent-tolerance properties, to create transgenic libraries in an E. coli host. We exposed cells containing the library to pinene, selecting for genes that improved tolerance. Importantly, we found that expressing the sigma factor RpoD from P. putida greatly expanded the diversity of tolerance genes recovered. With low expression of rpoDP.putida, we isolated a single pinene tolerance gene; with increased expression of the sigma factor our selection experiments returned multiple distinct tolerance mechanisms, including some that have been previously documented and also new mechanisms. Interestingly, high levels of rpoDP.putida induction resulted in decreased diversity. We found that the tolerance levels provided by some genes are highly sensitive to the level of induction of rpoDP.putida, while others provide tolerance across a wide range of rpoDP.putida levels. This method for unlocking diversity in tolerance screening using heterologous sigma factor expression was applicable to both plasmid and fosmid-based transgenic libraries. These results suggest that by controlling the expression of appropriate heterologous sigma factors, we can greatly increase the searchable genomic space within transgenic libraries.

  18. The alternative sigma factor sigma28 of Legionella pneumophila restores flagellation and motility to an Escherichia coli fliA mutant.

    PubMed Central

    Heuner, K; Hacker, J; Brand, B C

    1997-01-01

    Gene expression in Legionella pneumophila, the etiological agent of Legionnaires' disease, can be controlled by alternative forms of RNA polymerase programmed by distinct sigma factors. To understand the regulation of L. pneumophila flagellin expression, we cloned the sigma factor (FliA) of RNA polymerase responsible for the transcription of the flagellin gene, flaA. FliA is a member of the sigma28 class of alternative sigma factors identified in several bacterial genera. The gene fliA has been isolated from an expression library of L. pneumophila isolate Corby in Escherichia coli K-12. This library was transformed into a fliA mutant of E. coli K-12 containing a plasmid carrying the L. pneumophila-specific flaA promoter fused to the reporter gene luxAB. Screening the obtained transformants for luciferase activity, we isolated the major part of the fliA gene on a 1.64-kb fragment. This fragment was sequenced and used for reverse PCR in order to recover the complete fliA gene. The resulting 1.03-kb fragment was shown to contain the entire fliA gene. L. pneumophila FliA has 55 and 43% amino acid identity with the homologous sequences of Pseudomonas aeruginosa and E. coli. Furthermore, the L. pneumophila fliA gene was able to restore the flagellation and the motility defect of an E. coli fliA mutant. This result suggests that the L. pneumophila sigma28 protein can bind to the E. coli core RNA polymerase to direct transcription initiation from the flaA-specific promoter. PMID:8981975

  19. Co-ordinated regulation of the extracytoplasmic stress factor, sigmaE, with other Escherichia coli sigma factors by (p)ppGpp and DksA may be achieved by specific regulation of individual holoenzymes.

    PubMed

    Gopalkrishnan, Saumya; Nicoloff, Herve; Ades, Sarah E

    2014-08-01

    The E. coli alternative sigma factor, σ(E) , transcribes genes required to maintain the cell envelope and is activated by conditions that destabilize the envelope. σ(E) is also activated during entry into stationary phase in the absence of envelope stress by the alarmone (p)ppGpp. (p)ppGpp controls a large regulatory network, reducing expression of σ(70) -dependent genes required for rapid growth and activating σ(70) -dependent and alternative sigma factor-dependent genes required for stress survival. The DksA protein often potentiates the effects of (p)ppGpp. Here we examine regulation of σ(E) by (p)ppGpp and DksA following starvation for nutrients. We find that (p)ppGpp is required for increased σ(E) activity under all conditions tested, but the requirement for DksA varies. DksA is required during amino acid starvation, but is dispensable during phosphate starvation. In contrast, regulation of σ(S) is (p)ppGpp- and DksA-dependent under all conditions tested, while negative regulation of σ(70) is DksA- but not (p)ppGpp-dependent during phosphate starvation, yet requires both factors during amino acid starvation. These findings suggest that the mechanism of transcriptional regulation by (p)ppGpp and/or DksA cannot yet be explained by a unifying model and is specific to individual promoters, individual holoenzymes, and specific starvation conditions.

  20. Role of Sphingomonas sp. Strain Fr1 PhyR-NepR-σEcfG Cascade in General Stress Response and Identification of a Negative Regulator of PhyR▿†

    PubMed Central

    Kaczmarczyk, Andreas; Campagne, Sébastien; Danza, Francesco; Metzger, Lisa C.; Vorholt, Julia A.; Francez-Charlot, Anne

    2011-01-01

    The general stress response in Alphaproteobacteria was recently described to depend on the alternative sigma factor σEcfG, whose activity is regulated by its anti-sigma factor NepR. The response regulator PhyR, in turn, regulates NepR activity in a partner-switching mechanism according to which phosphorylation of PhyR triggers sequestration of NepR by the sigma factor-like effector domain of PhyR. Although genes encoding predicted histidine kinases can often be found associated with phyR, little is known about their role in modulation of PhyR phosphorylation status. We demonstrate here that the PhyR-NepR-σEcfG cascade is important for multiple stress resistance and competitiveness in the phyllosphere in a naturally abundant plant epiphyte, Sphingomonas sp. strain Fr1, and provide evidence that the partner switching mechanism is conserved. We furthermore identify a gene, designated phyP, encoding a predicted histidine kinase at the phyR locus as essential. Genetic epistasis experiments suggest that PhyP acts upstream of PhyR, keeping PhyR in an unphosphorylated, inactive state in nonstress conditions, strictly depending on the predicted phosphorylatable site of PhyP, His-341. In vitro experiments show that Escherichia coli inner membrane fractions containing PhyP disrupt the PhyR-P/NepR complex. Together with the fact that PhyP lacks an obvious ATPase domain, these results are in agreement with PhyP functioning as a phosphatase of PhyR, rather than a kinase. PMID:21949070

  1. Role of Sphingomonas sp. strain Fr1 PhyR-NepR-σEcfG cascade in general stress response and identification of a negative regulator of PhyR.

    PubMed

    Kaczmarczyk, Andreas; Campagne, Sébastien; Danza, Francesco; Metzger, Lisa C; Vorholt, Julia A; Francez-Charlot, Anne

    2011-12-01

    The general stress response in Alphaproteobacteria was recently described to depend on the alternative sigma factor σ(EcfG), whose activity is regulated by its anti-sigma factor NepR. The response regulator PhyR, in turn, regulates NepR activity in a partner-switching mechanism according to which phosphorylation of PhyR triggers sequestration of NepR by the sigma factor-like effector domain of PhyR. Although genes encoding predicted histidine kinases can often be found associated with phyR, little is known about their role in modulation of PhyR phosphorylation status. We demonstrate here that the PhyR-NepR-σ(EcfG) cascade is important for multiple stress resistance and competitiveness in the phyllosphere in a naturally abundant plant epiphyte, Sphingomonas sp. strain Fr1, and provide evidence that the partner switching mechanism is conserved. We furthermore identify a gene, designated phyP, encoding a predicted histidine kinase at the phyR locus as essential. Genetic epistasis experiments suggest that PhyP acts upstream of PhyR, keeping PhyR in an unphosphorylated, inactive state in nonstress conditions, strictly depending on the predicted phosphorylatable site of PhyP, His-341. In vitro experiments show that Escherichia coli inner membrane fractions containing PhyP disrupt the PhyR-P/NepR complex. Together with the fact that PhyP lacks an obvious ATPase domain, these results are in agreement with PhyP functioning as a phosphatase of PhyR, rather than a kinase.

  2. 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.

  3. Control of the Ferric Citrate Transport System of Escherichia coli: Mutations in Region 2.1 of the FecI Extracytoplasmic-Function Sigma Factor Suppress Mutations in the FecR Transmembrane Regulatory Protein

    PubMed Central

    Stiefel, Alfred; Mahren, Susanne; Ochs, Martina; Schindler, Petra T.; Enz, Sabine; Braun, Volkmar

    2001-01-01

    Transcription of the ferric citrate transport genes is initiated by binding of ferric citrate to the FecA protein in the outer membrane of Escherichia coli K-12. Bound ferric citrate does not have to be transported but initiates a signal that is transmitted by FecA across the outer membrane and by FecR across the cytoplasmic membrane into the cytoplasm, where the FecI extracytoplasmic-function (ECF) sigma factor becomes active. In this study, we isolated transcription initiation-negative missense mutants in the cytoplasmic region of FecR that were located at four sites, L13Q, W19R, W39R, and W50R, which are highly conserved in FecR-like open reading frames of the Pseudomonas aeruginosa, Pseudomonas putida, Bordetella pertussis, Bordetella bronchiseptica, and Caulobacter crescentus genomes. The cytoplasmic portion of the FecR mutant proteins, FecR1–85, did not interact with wild-type FecI, in contrast to wild-type FecR1–85, which induced FecI-mediated fecB transport gene transcription. Two missense mutations in region 2.1 of FecI, S15A and H20E, partially restored induction of ferric citrate transport gene induction of the fecR mutants by ferric citrate. Region 2.1 of ς70 is thought to bind RNA polymerase core enzyme; the residual activity of mutated FecI in the absence of FecR, however, was not higher than that of wild-type FecI. In addition, missense mutations in the fecI promoter region resulted in a twofold increased transcription in fecR wild-type cells and a partial restoration of fec transport gene transcription in the fecR mutants. The mutations reduced binding of the Fe2+ Fur repressor and as a consequence enhanced fecI transcription. The data reveal properties of the FecI ECF factor distinct from those of ς70 and further support the novel transcription initiation model in which the cytoplasmic portion of FecR is important for FecI activity. PMID:11114913

  4. Simultaneous inactivation of sigma factors B and D interferes with light acclimation of the cyanobacterium Synechocystis sp. strain PCC 6803.

    PubMed

    Pollari, Maija; Ruotsalainen, Virpi; Rantamäki, Susanne; Tyystjärvi, Esa; Tyystjärvi, Taina

    2009-06-01

    In cyanobacteria, gene expression is regulated mainly at the level of transcription initiation, which is mediated by the RNA polymerase holoenzyme. The RNA polymerase core is catalytically active, while the sigma factor recognizes promoter sequences. Group 2 sigma factors are similar to the principal sigma factor but are nonessential. Group 2 sigma factors SigB and SigD are structurally the most similar sigma factors in Synechocystis sp. strain PCC 6803. Under standard growth conditions, simultaneous inactivation of sigB and sigD genes did not affect the growth, but the photosynthesis and growth of the DeltasigBD strain were slower than in the control strain at double light intensity. Light-saturated electron transfer rates and the fluorescence and thermoluminescence measurements showed that photosynthetic light reactions are fully functional in the DeltasigBD strain, but absorption and 77 K emission spectra measurements suggest that the light-harvesting system of the DeltasigBD strain does not acclimate normally to higher light intensity. Furthermore, the DeltasigBD strain is more sensitive to photoinhibition under bright light because impaired upregulation of psbA genes leads to insufficient PSII repair.

  5. sigma(BldN), an extracytoplasmic function RNA polymerase sigma factor required for aerial mycelium formation in Streptomyces coelicolor A3(2).

    PubMed

    Bibb, M J; Molle, V; Buttner, M J

    2000-08-01

    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 sigma(BldN) holoenzyme in vitro.

  6. 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

  7. Sigma-1 receptor chaperone and brain-derived neurotrophic factor: emerging links between cardiovascular disease and depression.

    PubMed

    Hashimoto, Kenji

    2013-01-01

    Epidemiological studies have demonstrated a close relationship between depression and cardiovascular disease (CVD). Although it is known that the central nervous system (CNS) contributes to this relationship, the detailed mechanisms involved in this process remain unclear. Recent studies suggest that the endoplasmic reticulum (ER) molecular chaperone sigma-1 receptor and brain-derived neurotrophic factor (BDNF) play a role in the pathophysiology of CVD and depression. Several meta-analysis studies have showed that levels of BDNF in the blood of patients with major depressive disorder (MDD) are lower than normal controls, indicating that blood BDNF might be a biomarker for depression. Furthermore, blood levels of BDNF in patients with CVD are also lower than normal controls. A recent study using conditional BDNF knock-out mice in animal models of myocardial infarction highlighted the role of CNS-mediated mechanisms in the cardioprotective effects of BDNF. In addition, a recent study shows that decreased levels of sigma-1 receptor in the mouse brain contribute to the association between heart failure and depression. Moreover, sigma-1 receptor agonists, including the endogenous neurosteroid dehydroepiandosterone (DHEA) and the selective serotonin reuptake inhibitor (SSRI) fluvoxamine, show potent cardioprotective and antidepressive effects in rodents, via sigma-1 receptor stimulation. Interestingly, agonist activation of sigma-1 receptors increased the secretion of mature BDNF from its precursor proBDNF via chaperone activity in the ER. Given the role of ER stress in the pathophysiology of CVD and MDD, the author will discuss the potential link between sigma-1 receptors and BDNF-TrkB pathway in the pathophysiology of these two diseases. Finally, the author will make a case for potent sigma-1 receptor agonists and TrkB agonists as new potential therapeutic drugs for depressive patients with CVD.

  8. Alternative sigma factor SigK has a role in stress tolerance of group I Clostridium botulinum strain ATCC 3502.

    PubMed

    Dahlsten, Elias; Kirk, David; Lindström, Miia; Korkeala, Hannu

    2013-06-01

    The role of the alternative sigma factor SigK in cold and osmotic stress tolerance of Clostridium botulinum ATCC 3502 was demonstrated by induction of sigK after temperature downshift and exposure to hyperosmotic conditions and by impaired growth of the sigK mutants under the respective conditions.

  9. Integration of light and circadian signals that regulate chloroplast transcription by a nuclear-encoded sigma factor.

    PubMed

    Belbin, Fiona E; Noordally, Zeenat B; Wetherill, Sarah J; Atkins, Kelly A; Franklin, Keara A; Dodd, Antony N

    2017-01-01

    We investigated the signalling pathways that regulate chloroplast transcription in response to environmental signals. One mechanism controlling plastid transcription involves nuclear-encoded sigma subunits of plastid-encoded plastid RNA polymerase. Transcripts encoding the sigma factor SIG5 are regulated by light and the circadian clock. However, the extent to which a chloroplast target of SIG5 is regulated by light-induced changes in SIG5 expression is unknown. Moreover, the photoreceptor signalling pathways underlying the circadian regulation of chloroplast transcription by SIG5 are unidentified. We monitored the regulation of chloroplast transcription in photoreceptor and sigma factor mutants under controlled light regimes in Arabidopsis thaliana. We established that a chloroplast transcriptional response to light intensity was mediated by SIG5; a chloroplast transcriptional response to the relative proportions of red and far red light was regulated by SIG5 through phytochrome and photosynthetic signals; and the circadian regulation of chloroplast transcription by SIG5 was predominantly dependent on blue light and cryptochrome. Our experiments reveal the extensive integration of signals concerning the light environment by a single sigma factor to regulate chloroplast transcription. This may originate from an evolutionarily ancient mechanism that protects photosynthetic bacteria from high light stress, which subsequently became integrated with higher plant phototransduction networks.

  10. Resonance assignments of the periplasmic domain of a cellulose-sensing trans-membrane anti-sigma factor from Clostridium thermocellum.

    PubMed

    Ding, Xiaoke; Chen, Chao; Cui, Qiu; Li, Wenli; Feng, Yingang

    2015-10-01

    The cellulosome of Clostridium thermocellum is an elegant and efficient multi-enzyme complex for degrading lignocellulose. The cellulosome contains several dozens of carbohydrate hydrolysis enzymes, which are regulated by the presence of environmental substrates through several pairs of sigma and anti-sigma factors. The anti-sigma factors sense the presence of substrates and transduce the signals into the cell. The sigma factors are then released from the corresponding anti-sigma factors, and they recruit RNA polymerase to transcribe specific cellulosomal genes. However, it is not clear how the extracellular signals are transduced into the cell by the anti-sigma factors. The anti-sigma factors of C. thermocellum contain an N-terminal intracellular domain, a trans-membrane helix, a periplasmic domain, a proline-rich region which is probably required for crossing the cell wall, and a C-terminal carbohydrate-binding domain or glycoside hydrolase domain. The periplasmic domain may play a key role in signal transduction; however, its three-dimensional structure is still unknown. Here we report the NMR resonance assignments of the periplasmic domain of anti-sigma factor RsgI2 from C. thermocellum as a basis for further structural determination and functional studies.

  11. 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

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

    DOE PAGES

    Li, Jie; Nakayasu, Ernesto S.; Overall, Christopher C.; ...

    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

  13. 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.

  14. 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

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

    PubMed

    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

    2015-04-03

    The alternative sigma factor E (σ(E)) is critical for response to extracytoplasmic stress in Salmonella. Extensive studies have been conducted on σ(E)-regulated gene expression, particularly at the transcriptional level. Increasing evidence suggests however that σ(E) 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 σ(E) 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 σ(E) combining all three conditions. In different growth conditions, σ(E) 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 σ(E) and found that post-transcriptional regulation was responsible for a majority of changes observed in the σ(E)-regulated proteome. Further, comparison of transcriptomic and proteomic data from hfq mutant of Salmonella demonstrated that σ(E)-mediated post-transcriptional regulation was partially dependent on the RNA-binding protein Hfq.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. Roles of chloroplast RNA polymerase sigma factors in chloroplast development and stress response in higher plants.

    PubMed

    Kanamaru, Kengo; Tanaka, Kan

    2004-11-01

    Chloroplast transcription in higher plants is performed by two types of RNA polymerases, plastid-encoded RNA polymerase (PEP) and nuclear-encoded RNA polymerase (NEP). PEP is a eubacteria-type multisubunit enzyme whose catalytic core subunits are encoded by the chloroplast genome, whereas NEP is the nuclear encoded T7 phage-type single subunit enzyme. PEP is critical for the biogenesis and maintenance of chloroplasts, and is finely tuned by the nuclear encoded sigma subunits. Of the six Arabidopsis sigma subunits, SIG2 is involved in the transcription of several chloroplast tRNA genes, including trnE encoding tRNA-Glu. SIG2 possibly couples translation and pigment synthesis in chloroplasts. On the other hand, SIG5 is induced by various stresses and contributes to repair of damaged photosystem II (PSII) through transcription of the psbD and psbC genes. Thus target genes and the physiological role of each sigma subunit are becoming clearer.

  1. 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.

  2. 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

  3. Alternative Sigma Factor Over-Expression Enables Heterologous Expression of a Type II Polyketide Biosynthetic Pathway in Escherichia coli

    PubMed Central

    Stevens, David Cole; Conway, Kyle R.; Pearce, Nelson; Villegas-Peñaranda, Luis Roberto; Garza, Anthony G.; Boddy, Christopher N.

    2013-01-01

    Background Heterologous expression of bacterial biosynthetic gene clusters is currently an indispensable tool for characterizing biosynthetic pathways. Development of an effective, general heterologous expression system that can be applied to bioprospecting from metagenomic DNA will enable the discovery of a wealth of new natural products. Methodology We have developed a new Escherichia coli-based heterologous expression system for polyketide biosynthetic gene clusters. We have demonstrated the over-expression of the alternative sigma factor σ54 directly and positively regulates heterologous expression of the oxytetracycline biosynthetic gene cluster in E. coli. Bioinformatics analysis indicates that σ54 promoters are present in nearly 70% of polyketide and non-ribosomal peptide biosynthetic pathways. Conclusions We have demonstrated a new mechanism for heterologous expression of the oxytetracycline polyketide biosynthetic pathway, where high-level pleiotropic sigma factors from the heterologous host directly and positively regulate transcription of the non-native biosynthetic gene cluster. Our bioinformatics analysis is consistent with the hypothesis that heterologous expression mediated by the alternative sigma factor σ54 may be a viable method for the production of additional polyketide products. PMID:23724102

  4. Alternative zinc-binding sites explain the redox sensitivity of zinc-containing anti-sigma factors.

    PubMed

    Heo, Lim; Cho, Yoo-Bok; Lee, Myeong Sup; Roe, Jung-Hye; Seok, Chaok

    2013-09-01

    Certain bacterial zinc-containing anti-sigma (ZAS) factors respond sensitively to thiol-induced oxidative stress by undergoing conformational changes, which in turn reduce binding affinities for their cognate sigma factors. This redox sensitivity provides a mechanism for coping with oxidative stress by activating the transcription of antioxidant genes. Not all ZAS proteins are redox-sensitive, but the mechanism of redox sensitivity is not fully understood. Here we propose that alternative zinc-binding sites determine redox sensitivity. To support this proposal, we performed protein modeling and zinc docking on redox-sensitive and redox-insensitive ZAS proteins complexed with their cognate sigma factors. At least one strong alternative zinc-binding pocket was detected for all known redox-sensitive ZAS factors in actinomycetes, while no strong alternative zinc-binding pocket was identified in redox-insensitive ZAS factors, except for one controversial case. This hypothesis of alternative zinc-binding sites can also explain residue-specific contributions to the redox sensitivity of RsrA, a redox-sensing ZAS protein from Streptomyces coelicolor, for which alanine mutagenesis experiments are available. Our results suggest a mechanistic model for redox sensitivity as follows: zinc ion can probabilistically occupy multiple sites in redox-sensitive ZAS proteins, increasing the susceptibility of zinc-coordinating cysteine residues to oxidation. This picture of probabilistic zinc occupation agrees with a previous structure and energy analysis on zinc finger proteins, and thus it may be more widely applicable to other classes of reactive zinc-binding proteins.

  5. SpoIIE governs the phosphorylation state of a protein regulating transcription factor sigma F during sporulation in Bacillus subtilis.

    PubMed Central

    Arigoni, F; Duncan, L; Alper, S; Losick, R; Stragier, P

    1996-01-01

    Cell-specific activation of the transcription factor sigma F during sporulation in Bacillus subtilis is controlled by a regulatory pathway involving the proteins SpoIIE, SpoIIAA, and SpoIIAB. SpoIIAB is an antagonist of sigma F, and SpoIIAA, which is capable of overcoming SpoIIAB-mediated inhibition of sigma F, is an antagonist of SpoIIAB. SpoIIAA is, in turn, negatively regulated by SpoIIAB, which phosphorylates SpoIIAA on serine 58. SpoIIAA is also positively regulated by SpoIIE, which dephosphorylates SpoIIAA-P, the phosphorylated form of SpoIIAA. Here, isoelectric focusing and Western blot analysis were used to examine the phosphorylation state of SpoIIAA in vivo. SpoIIAA was found to be largely in the phosphorylated state during sporulation in wild-type cells but a significant portion of the protein that was unphosphorylated could also be detected. Consistent with the idea that SpoIIE governs dephosphorylation of SpoIIAA-P, SpoIIAA was entirely in the phosphorylated state in spoIIE mutant cells. Conversely, overexpression of spoIIE led to an increase in the ratio of unphosphorylated SpoIIAA to SpoIIAA-P and caused inappropriate activation of sigma F in the predivisional sporangium. We also show that a mutant form of SpoIIAA (SpoIIAA-S58T) in which serine 58 was replaced with threonine was present exclusively as SpoIIAA-P, a finding that confirms previous biochemical evidence that the mutant protein is an effective substrate for the SpoIIAB kinase but that SpoIIAA-S58T-P cannot be dephosphorylated by SpoIIE. We conclude that SpoIIE plays a crucial role in controlling the phosphorylation state of SpoIIAA during sporulation and thus in governing the cell-specific activation of sigma F. Images Fig. 1 Fig. 2 Fig. 4 PMID:8622920

  6. Loss of sigma factor RpoN increases intestinal colonization of Vibrio parahaemolyticus in an adult mouse model.

    PubMed

    Whitaker, W Brian; Richards, Gary P; Boyd, E Fidelma

    2014-02-01

    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.

  7. 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

  8. ECF micropump fabricated by electroforming with novel self-aligned micro-molding technology

    NASA Astrophysics Data System (ADS)

    Han, D.; Kim, J. W.; Yokota, S.; Edamura, K.

    2015-12-01

    This paper proposes and presents a novel ECF (electro-conjugate fluid) micropump with TPSEs (triangular prism and slit electrode pair) fabricated by electroforming process using newly developed self-aligned micro molds. ECF is a kind of functional and dielectric fluid. ECF micropump is based on the principle of ECF jet, which is a powerful and active jet flow generated between electrodes immerged in ECF, when high DC voltage is applied to the electrodes. Our previous research experimentally demontrated that the ECF micropump had high power density thanks to the 2D-integraton (serialized integration and paralleled integration) of our proposed MEMS fabrication method by using micro-molding and electroplating. Moreover, it was also proved that higher aspect ratio of TPSEs by the multilayer fabrication process resulted in higher flow rate of the ECF micropump. However, the multilayer fabrication has demerit to require precise alignment that is time-consuming and extremely difficult to be met. In order to improve alignment accuracy and alleviate fabrication difficulty, this paper proposes a novel self-aligned MEMS fabrication process for high aspect ratio TPSEs. The ECF micropump by this newly-proposed MEMS process was successfully fabricated and the feasibility was proved by experimentally investigating output performance of the ECF micropump.

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

    PubMed

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

    1997-05-01

    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.

  10. A Role for Sigma Factor σE in Corynebacterium pseudotuberculosis Resistance to Nitric Oxide/Peroxide Stress

    PubMed Central

    Pacheco, Luis G. C.; Castro, Thiago L. P.; Carvalho, Rodrigo D.; Moraes, Pablo M.; Dorella, Fernanda A.; Carvalho, Natália B.; Slade, Susan E.; Scrivens, James H.; Feelisch, Martin; Meyer, Roberto; Miyoshi, Anderson; Oliveira, Sergio C.; Dowson, Christopher G.; Azevedo, Vasco

    2012-01-01

    Pathogenic intracellular bacteria can respond to antimicrobial mechanisms of the host cell through transient activation of stress-responsive genes by alternative sigma (σ) factors of the RNA polymerase. We evaluated the contribution of the extracytoplasmic function sigma factor σE for Corynebacterium pseudotuberculosis resistance to stress conditions resembling those found intracellularly during infection. A sigE-null mutant strain (ΔsigE) of this bacterium was more susceptible in vitro to acidic pH, cell surface stressors, and biologically relevant concentrations of nitric oxide (NO). The same mutant strain was unable to persist in C57BL/6 mice but remained infective in mice lacking inducible nitric oxide synthase (iNOS), confirming the significance of σE for resistance to nitric oxide/peroxide stress in vivo. High-throughput proteomic analysis identified NO-responsive extracellular proteins of C. pseudotuberculosis and demonstrated the participation of σE in composition of this bacterium’s exoproteome. PMID:22514549

  11. 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

  12. 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

  13. 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

  14. A PP2C phosphatase containing a PAS domain is required to convey signals of energy stress to the sigmaB transcription factor of Bacillus subtilis.

    PubMed

    Vijay, K; Brody, M S; Fredlund, E; Price, C W

    2000-01-01

    The sigmaB transcription factor of the bacterium Bacillus subtilis is activated by growth-limiting energy or environmental challenge to direct the synthesis of more than 100 general stress proteins. Although the signal transduction pathway that conveys these stress signals to sigmaB is becoming increasingly well understood, how environmental or energy stress signals enter this pathway remains unknown. We show here that two PP2C serine phosphatases - RsbP, which is required for response to energy stress, and RsbU, which is required for response to environmental stress - each converge on the RsbV regulator of sigmaB. According to the current understanding of sigmaB regulation, in unstressed cells the phosphorylated RsbV anti-anti-sigma is unable to complex the RsbW anti-sigma, which is then free to bind and inactivate sigmaB. We can now advance the model that either PP2C phosphatase, when triggered by its particular class of stress, can remove the phosphate from RsbV and thereby activate sigmaB. The action of the previously described RsbU is known to be controlled by dedicated upstream signalling components that are activated by environmental stress. The action of the RsbP phosphatase described here requires an energy stress, which we suggest is sensed, at least in part, by the PAS domain in the amino-terminal region of the RsbP phosphatase. In other bacterial signalling proteins, similar PAS domains and their associated chromophores directly sense changes in intracellular redox potential to control the activity of a linked output domain.

  15. A Mycobacterium tuberculosis Sigma Factor Network Responds to Cell-Envelope Damage by the Promising Anti-Mycobacterial Thioridazine

    PubMed Central

    Dutta, Noton K.; Mehra, Smriti; Kaushal, Deepak

    2010-01-01

    Background Novel therapeutics are urgently needed to control tuberculosis (TB). Thioridazine (THZ) is a candidate for the therapy of multidrug and extensively drug-resistant TB. Methodology/Principal Findings We studied the impact of THZ on Mycobacterium tuberculosis (Mtb) by analyzing gene expression profiles after treatment at the minimal inhibitory (1x MIC) or highly inhibitory (4x MIC) concentrations between 1–6 hours. THZ modulated the expression of genes encoding membrane proteins, efflux pumps, oxido-reductases and enzymes involved in fatty acid metabolism and aerobic respiration. The Rv3160c-Rv3161c operon, a multi-drug transporter and the Rv3614c/3615c/3616c regulon, were highly induced in response to THZ. A significantly high number of Mtb genes co-expressed with σB (the σB regulon) was turned on by THZ treatment. σB has recently been shown to protect Mtb from envelope-damage. We hypothesized that THZ damages the Mtb cell-envelope, turning on the expression of the σB regulon. Consistent with this hypothesis, we present electron-microscopy data which shows that THZ modulates cell-envelope integrity. Moreover, the Mtb mutants in σH and σE, two alternate stress response sigma factors that induce the expression of σB, exhibited higher sensitivity to THZ, indicating that the presence and expression of σB allows Mtb to resist the impact of THZ. Conditional induction of σB levels increased the survival of Mtb in the presence of THZ. Conclusions/Significance THZ targets different pathways and can thus be used as a multi-target inhibitor itself as well as provide strategies for multi-target drug development for combination chemotherapy. Our results show that the Mtb sigma factor network comprising of σH, σE and σB plays a crucial role in protecting the pathogen against cell-envelope damage. PMID:20386700

  16. 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.

  17. 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

  18. Role of sigma B factor in the alkaline tolerance response of Listeria monocytogenes 10403S and cross-protection against subsequent ethanol and osmotic stress.

    PubMed

    Giotis, Efstathios S; Julotok, Mudcharee; Wilkinson, Brian J; Blair, Ian S; McDowell, David A

    2008-07-01

    Many of the considerable abilities of Listeria monocytogenes to persist and grow in a wide range of adverse environmental conditions are thought to be at least partly under the control of the alternative sigma factor (sigmaB), encoded by the sigB gene. However, little is known about the role of this master regulon in the impressive ability of Listeria to persist and grow under conditions of alkaline pH. In this study, Northern blot analysis of parent Listeria mRNA revealed that alkali adaptation (pH 9.5 for 1 h) significantly increased the expression of sigB-derived mRNA. The study included a comparison of the relative survival of mid-exponential populations of adapted and nonadapted parent type (sigmaB expressing) and mutant (not sigmaB expressing, deltasigB) Listeria strains during subsequent alkaline (pH 12.0), osmotic (25% NaCl, wt/vol), or ethanol (16.5%) stress. Alkali-adapted parent strains were more resistant to pH 12.0 than were adapted deltasigB type strains, but both alkali-adapted parent and deltasigB strains were more resistant to pH 12.0 than were nonadapted strains. Alkali-adapted parent strains were more resistant to osmotic stress than were adapted deltasigB type strains. No significant differences in viability were observed between alkali-adapted parent and deltasigB strains after ethanol stress, suggesting that cross-protection against osmotic stress is mediated by sigmaB whereas cross-protection against ethanol is sigmaB independent. Overall, alkali-induced cross-protection against osmotic and ethanol challenges may have serious implications for food safety and human health because such stress conditions are routinely used as part of food preservation and surface cleaning processes.

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

    PubMed

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

    2015-07-03

    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 [(3)H]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.

  20. 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

  1. 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

  2. The actinobacterial transcription factor RbpA binds to the principal sigma subunit of RNA polymerase.

    PubMed

    Tabib-Salazar, Aline; Liu, Bing; Doughty, Philip; Lewis, Richard A; Ghosh, Somadri; Parsy, Marie-Laure; Simpson, Peter J; O'Dwyer, Kathleen; Matthews, Steve J; Paget, Mark S

    2013-06-01

    RbpA is a small non-DNA-binding transcription factor that associates with RNA polymerase holoenzyme and stimulates transcription in actinobacteria, including Streptomyces coelicolor and Mycobacterium tuberculosis. RbpA seems to show specificity for the vegetative form of RNA polymerase as opposed to alternative forms of the enzyme. Here, we explain the basis of this specificity by showing that RbpA binds directly to the principal σ subunit in these organisms, but not to more diverged alternative σ factors. Nuclear magnetic resonance spectroscopy revealed that, although differing in their requirement for structural zinc, the RbpA orthologues from S. coelicolor and M. tuberculosis share a common structural core domain, with extensive, apparently disordered, N- and C-terminal regions. The RbpA-σ interaction is mediated by the C-terminal region of RbpA and σ domain 2, and S. coelicolor RbpA mutants that are defective in binding σ are unable to stimulate transcription in vitro and are inactive in vivo. Given that RbpA is essential in M. tuberculosis and critical for growth in S. coelicolor, these data support a model in which RbpA plays a key role in the σ cycle in actinobacteria.

  3. Sigma Factor Regulated Cellular Response in a Non-solvent Producing Clostridium beijerinckii Degenerated Strain: A Comparative Transcriptome Analysis

    PubMed Central

    Zhang, Yan; Jiao, Shengyin; Lv, Jia; Du, Renjia; Yan, Xiaoni; Wan, Caixia; Zhang, Ruijuan; Han, Bei

    2017-01-01

    Clostridium beijerinckii DG-8052, derived from NCIMB 8052, cannot produce solvent or form spores, a phenomenon known as degeneration. To explore the mechanisms of degeneration at the gene level, transcriptomic profiles of the wild-type 8052 and DG-8052 strains were compared. Expression of 5168 genes comprising 98.6% of the genome was assessed. Interestingly, 548 and 702 genes were significantly up-regulated in the acidogenesis and solventogenesis phases of DG-8052, respectively, and mainly responsible for the phosphotransferase system, sugar metabolic pathways, and chemotaxis; meanwhile, 699 and 797 genes were significantly down-regulated, respectively, and mainly responsible for sporulation, oxidoreduction, and solventogenesis. The functions of some altered genes, including 286 and 333 at the acidogenesis and solventogenesis phases, respectively, remain unknown. Dysregulation of the fermentation machinery was accompanied by lower transcription levels of glycolysis rate-limiting enzymes (pfk and pyk), and higher transcription of cell chemotaxis genes (cheA, cheB, cheR, cheW, and cheY), controlled mainly by σ54 at acidogenesis. Meanwhile, abnormal spore formation was associated with repressed spo0A, sigE, sigF, sigG, and sigK which are positively regulated by σ70, and correspondingly inhibited expression of CoA-transferase at the solventogenesis phase. These findings indicated that morphological and physiological changes in the degenerated Clostridium strain may be related to altered expression of sigma factors, providing valuable targets for strain development of Clostridium species. PMID:28194137

  4. 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

  5. Structure of the RNA polymerase assembly factor Crl and identification of its interaction surface with sigma S.

    PubMed

    Banta, Amy B; Cuff, Marianne E; Lin, Hueylie; Myers, Angela R; Ross, Wilma; Joachimiak, Andrzej; Gourse, Richard L

    2014-09-01

    Bacteria utilize multiple sigma factors that associate with core RNA polymerase (RNAP) to control transcription in response to changes in environmental conditions. In Escherichia coli and Salmonella enterica, Crl positively regulates the σ(S) regulon by binding to σ(S) to promote its association with core RNAP. We recently characterized the determinants in σ(S) responsible for specific binding to Crl. However, little is known about the determinants in Crl required for this interaction. Here, we present the X-ray crystal structure of a Crl homolog from Proteus mirabilis in conjunction with in vivo and in vitro approaches that probe the Crl-σ(S) interaction in E. coli. We show that the P. mirabilis, Vibrio harveyi, and E. coli Crl homologs function similarly in E. coli, indicating that Crl structure and function are likely conserved throughout gammaproteobacteria. We utilize phylogenetic conservation and bacterial two-hybrid analyses to predict residues in Crl important for the interaction with σ(S). The results of p-benzoylphenylalanine (BPA)-mediated UV cross-linking studies further support the model in which an evolutionarily conserved central cleft is the surface on Crl that binds to σ(S). Within this conserved binding surface, we identify a key residue in Crl that is critical for activation of Eσ(S)-dependent transcription in vivo and in vitro. Our study provides a physical basis for understanding the σ(S)-Crl interaction.

  6. Nerve growth factor-induced neurite sprouting in PC12 cells involves sigma-1 receptors: implications for antidepressants.

    PubMed

    Takebayashi, Minoru; Hayashi, Teruo; Su, Tsung-Ping

    2002-12-01

    One theory concerning the action of antidepressants relates to the drugs' ability to induce an adaptive plasticity in neurons such as neurite sprouting. Certain antidepressants are known to bind to sigma-1 receptors (Sig-1R) with high affinity. Sig-1R are dynamic endoplasmic reticulum proteins that are highly concentrated at the tip of growth cones in cultured cells. We therefore tested the hypotheses that Sig-1R might participate in the neurite sprouting and that antidepressants with Sig-1R affinity may promote the neuronal sprouting via Sig-1R. The prototypic Sig-1R agonist (+)-pentazocine [(+)PTZ], as well as the Sig-1R-active antidepressants imipramine and fluvoxamine, although ineffective by themselves, were found to enhance the nerve growth factor (NGF)-induced neurite sprouting in PC12 cells in a dose-dependent manner. A Sig-1R antagonist N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE100) blocked the enhancements caused by these Sig-1R agonists. In separate experiments, we found that NGF dose and time dependently increased Sig-1R in PC12 cells. Chronic treatment of cells with (+)PTZ, imipramine, or fluvoxamine also increased Sig-1R. These latter results suggested that NGF induces the neurite sprouting by increasing Sig-1R. Indeed, the overexpression of Sig-1R per se in PC12 cells enhanced the NGF-induced neurite sprouting. Furthermore, antisense deoxyoligonucleotides directed against Sig-1R attenuated the NGF-induced neurite sprouting. Thus, when taken together, our results indicate that Sig-1R play an important role in the NGF-induced neurite sprouting and that certain antidepressants may facilitate neuronal sprouting in the brain via Sig-1R.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Substitution of a highly conserved histidine in the Escherichia coli heat shock transcription factor, sigma32, affects promoter utilization in vitro and leads to overexpression of the biofilm-associated flu protein in vivo.

    PubMed

    Kourennaia, Olga V; Dehaseth, Pieter L

    2007-12-01

    The heat shock sigma factor (sigma(32) in Escherichia coli) directs the bacterial RNA polymerase to promoters of a specific sequence to form a stable complex, competent to initiate transcription of genes whose products mitigate the effects of exposure of the cell to high temperatures. The histidine at position 107 of sigma(32) is at the homologous position of a tryptophan residue at position 433 of the main sigma factor of E. coli, sigma(70). This tryptophan is essential for the strand separation step leading to the formation of the initiation-competent RNA polymerase-promoter complex. The heat shock sigma factors of all gammaproteobacteria sequenced have a histidine at this position, while in the alpha- and deltaproteobacteria, it is a tryptophan. In vitro the alanine-for-histidine substitution at position 107 (H107A) destabilizes complexes between the GroE promoter and RNA polymerase containing sigma(32), implying that H107 plays a role in formation or maintenance of the strand-separated complex. In vivo, the H107A substitution in sigma(32) impedes recovery from heat shock (exposure to 42 degrees C), and it also leads to overexpression at lower temperatures (30 degrees C) of the Flu protein, which is associated with biofilm formation.

  12. The nucleotide sequence of the nitrogen-regulation gene ntrA of Klebsiella pneumoniae and comparison with conserved features in bacterial RNA polymerase sigma factors.

    PubMed Central

    Merrick, M J; Gibbins, J R

    1985-01-01

    The nucleotide sequence of the Klebsiella pneumoniae ntrA gene has been determined. NtrA encodes a 53,926 Dalton acidic polypeptide; a calculated molecular weight which is significantly lower than that determined by SDS polyacrylamide gel analysis. NtrA is followed by another open-reading frame (orf) of at least 75 amino acids. In the spacer region between ntrA and orf there are no apparent transcription termination or promoter sequences and therefore orf may be co-transcribed with ntrA. Previous authors have proposed that NtrA could act as an RNA polymerase sigma factor but the NtrA amino acid sequence does not show a high level of homology to any known sigma factor. However analysis of sequences of five sigma factors from E. coli and B. subtilis has identified two conserved sequences at the C-terminal end of all these polypeptides. These sequences resemble those found in known site-specific DNA-binding domains and may be involved in recognition of conserved -35 and -10 promoter sequences. A similar pair of sequences is present at the C-terminus of NtrA and could play a role in recognition of ntr-activatable promoters. Images PMID:2999700

  13. Mutations in the primary sigma factor σA and termination factor rho that reduce susceptibility to cell wall antibiotics.

    PubMed

    Lee, Yong Heon; Helmann, John D

    2014-11-01

    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 (sigA(G336C)), in the domain that recognizes the -35 promoter region, is sufficient to reduce susceptibility to VAN and works cooperatively with the rho(G56C) substitution to increase CEF resistance. Transcriptome analyses revealed that the sigA(G336C) substitution has wide-ranging effects, including elevated expression of the general stress σ factor (σ(B)) 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.

  14. 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…

  15. Structure-based design of potent small-molecule binders to the S-component of the ECF transporter for thiamine.

    PubMed

    Swier, Lotteke J Y M; Monjas, Leticia; Guskov, Albert; de Voogd, Alrik R; Erkens, Guus B; Slotboom, Dirk J; Hirsch, Anna K H

    2015-03-23

    Energy-coupling factor (ECF) transporters are membrane-protein complexes that mediate vitamin uptake in prokaryotes. They bind the substrate through the action of a specific integral membrane subunit (S-component) and power transport by hydrolysis of ATP in the three-subunit ECF module. Here, we have studied the binding of thiamine derivatives to ThiT, a thiamine-specific S-component. We designed and synthesized derivatives of thiamine that bind to ThiT with high affinity; this allowed us to evaluate the contribution of the functional groups to the binding affinity. We determined six crystal structures of ThiT in complex with our derivatives. The structure of the substrate-binding site in ThiT remains almost unchanged despite substantial differences in affinity. This work indicates that the structural organization of the binding site is robust and suggests that substrate release, which is required for transport, requires additional changes in conformation in ThiT that might be imposed by the ECF module.

  16. A Membrane-Embedded Amino Acid Couples the SpoIIQ Channel Protein to Anti-Sigma Factor Transcriptional Repression during Bacillus subtilis Sporulation

    PubMed Central

    Flanagan, Kelly A.; Comber, Joseph D.; Mearls, Elizabeth; Fenton, Colleen; Wang Erickson, Anna F.

    2016-01-01

    ABSTRACT SpoIIQ is an essential component of a channel connecting the developing forespore to the adjacent mother cell during Bacillus subtilis sporulation. This channel is generally required for late gene expression in the forespore, including that directed by the late-acting sigma factor σG. Here, we present evidence that SpoIIQ also participates in a previously unknown gene regulatory circuit that specifically represses expression of the gene encoding the anti-sigma factor CsfB, a potent inhibitor of σG. The csfB gene is ordinarily transcribed in the forespore only by the early-acting sigma factor σF. However, in a mutant lacking the highly conserved SpoIIQ transmembrane amino acid Tyr-28, csfB was also aberrantly transcribed later by σG, the very target of CsfB inhibition. This regulation of csfB by SpoIIQ Tyr-28 is specific, given that the expression of other σF-dependent genes was unaffected. Moreover, we identified a conserved element within the csfB promoter region that is both necessary and sufficient for SpoIIQ Tyr-28-mediated inhibition. These results indicate that SpoIIQ is a bifunctional protein that not only generally promotes σG activity in the forespore as a channel component but also specifically maximizes σG activity as part of a gene regulatory circuit that represses σG-dependent expression of its own inhibitor, CsfB. Finally, we demonstrate that SpoIIQ Tyr-28 is required for the proper localization and stability of the SpoIIE phosphatase, raising the possibility that these two multifunctional proteins cooperate to fine-tune developmental gene expression in the forespore at late times. IMPORTANCE Cellular development is orchestrated by gene regulatory networks that activate or repress developmental genes at the right time and place. Late gene expression in the developing Bacillus subtilis spore is directed by the alternative sigma factor σG. The activity of σG requires a channel apparatus through which the adjacent mother cell provides

  17. Translational stimulation by reovirus polypeptide sigma 3: substitution for VAI RNA and inhibition of phosphorylation of the alpha subunit of eukaryotic initiation factor 2.

    PubMed Central

    Lloyd, R M; Shatkin, A J

    1992-01-01

    COS cells transfected with plasmids that activate DAI depend on expression of virus-associated I (VAI) RNA to prevent the inhibitory effects of the alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha) kinase (DAI) and restore the translation of vector-derived dihydrofolate reductase mRNA. This VAI RNA requirement could be completely replaced by reovirus polypeptide sigma 3, consistent with its double-stranded RNA (dsRNA)-binding activity. S4 gene transfection of 293 cells also partially restored adenovirus protein synthesis after infection with the VAI-negative dl331 mutant. In dl331-infected 293 cells, eIF-2 alpha was present mainly in the acidic, phosphorylated form, and trans complementation with polypeptide sigma 3 or VAI RNA decreased the proportion of eIF-2 alpha (P) from approximately 85 to approximately 30%. Activation of DAI by addition of dsRNA to extracts of S4 DNA-transfected COS cells required 10-fold-higher levels of dsRNA than extracts made from cells that were not producing polypeptide sigma 3. In extracts of reovirus-infected mouse L cells, the concentration of dsRNA needed to activate DAI was dependent on the viral serotype used for the infection. Although the proportion of eIF-2 alpha (P) was greater than that in uninfected cells, most of the factor remained in the unphosphorylated form, even at 16 h after infection, consistent with the partial inhibition of host protein synthesis observed with all three viral serotypes. The results indicate that reovirus polypeptide sigma 3 participates in the regulation of protein synthesis by modulating DAI and eIF-2 alpha phosphorylation. Images PMID:1433498

  18. Polyphosphate kinase 1, a central node in the stress response network of Mycobacterium tuberculosis, connects the two-component systems MprAB and SenX3-RegX3 and the extracytoplasmic function sigma factor, sigma E.

    PubMed

    Sanyal, Sourav; Banerjee, Srijon Kaushik; Banerjee, Rajdeep; Mukhopadhyay, Jayanta; Kundu, Manikuntala

    2013-10-01

    Polyphosphate (poly P) metabolism regulates the stress response in mycobacteria. Here we describe the regulatory architecture of a signal transduction system involving the two-component system (TCS) SenX3-RegX3, the extracytoplasmic function sigma factor sigma E (SigE) and the poly P-synthesizing enzyme polyphosphate kinase 1 (PPK1). The ppk1 promoter of Mycobacterium tuberculosis is activated under phosphate starvation. This is attenuated upon deletion of an imperfect palindrome likely representing a binding site for the response regulator RegX3, a component of the two-component system SenX3-RegX3 that responds to phosphate starvation. Binding of phosphorylated RegX3 to this site was confirmed by electrophoretic mobility shift assay. The activity of the ppk1 promoter was abrogated upon deletion of a putative SigE binding site. Pull-down of SigE from M. tuberculosis lysates of phosphate-starved cells with a biotinylated DNA harbouring the SigE binding site confirmed the likely binding of SigE to the ppk1 promoter. In vitro transcription corroborated the involvement of SigE in ppk1 transcription. Finally, the overexpression of RseA (anti-SigE) attenuated ppk1 expression under phosphate starvation, supporting the role of SigE in ppk1 transcription. The regulatory elements identified in ppk1 transcription in this study, combined with our earlier observation that PPK1 is itself capable of regulating sigE expression via the MprAB TCS, suggest the presence of multiple positive-feedback loops in this signalling circuit. In combination with the sequestering effect of RseA, we hypothesize that this architecture could be linked to bistability in the system that, in turn, could be a key element of persistence in M. tuberculosis.

  19. Enhancement of Chlorella vulgaris harvesting via the electro-coagulation-flotation (ECF) method.

    PubMed

    Wong, Y K; Ho, Y H; Leung, H M; Ho, K C; Yau, Y H; Yung, K K L

    2016-12-30

    This article explores the potential of using an electro-coagulation-flotation (ECF) harvester to allow flotation of microalgae cells for surface harvesting. A response surface methodology (RSM) model was used to optimize ECF harvesting by adjusting electrode plate material, electrode plate number, charge of the electrodes, electrolyte concentration, and pH value of the culture solution. The result revealed that three aluminum electrode plates (one anode and two cathodes), brine solution (8 g/L), and acidity (pH = 4) of culture solution (optimized ECF harvester) The highest flocculant concentration was measured at 2966 mg/L after 60 min and showed a 79.8 % increase of flocculation concentration. Such results can provide a basis for designing a large-scale microalgae harvester for commercial use in the future.

  20. Sigma factor genes sigC, sigE, and sigG are upregulated in heterocysts of the cyanobacterium Anabaena sp. strain PCC 7120.

    PubMed

    Aldea, M Ramona; Mella-Herrera, Rodrigo A; Golden, James W

    2007-11-01

    We used gfp transcriptional fusions to investigate the regulation of eight sigma factor genes during heterocyst development in the cyanobacterium Anabaena sp. strain PCC 7120. Reporter strains containing gfp fusions with the upstream regions of sigB2, sigD, sigI, and sigJ did not show developmental regulation. Time-lapse microscopy of sigC, sigE, and sigG reporter strains showed increased green fluorescent protein fluorescence in differentiating cells at 4 h, 16 h, and 9 h, respectively, after nitrogen step down.

  1. Crystal structure of a folate energy-coupling factor transporter from Lactobacillus brevis.

    PubMed

    Xu, Ke; Zhang, Minhua; Zhao, Qin; Yu, Fang; Guo, Hui; Wang, Chengyuan; He, Fangyuan; Ding, Jianping; Zhang, Peng

    2013-05-09

    ATP-binding cassette (ABC) transporters, composed of importers and exporters, form one of the biggest protein superfamilies that transport a variety of substrates across the membrane, powered by ATP hydrolysis. Most ABC transporters are composed of two transmembrane domains and two cytoplasmic nucleotide-binding domains. Also, importers from prokaryotes usually have extra solute-binding proteins in the periplasm that are responsible for the binding of substrates. Structures of importers have been reported that suggested a two-state model for the transport mechanism. Energy-coupling factor (ECF) transporters belong to a new class of ATP-binding cassette importers. Each ECF transporter comprises an energy-coupling module consisting of a transmembrane T protein (EcfT), two nucleotide-binding proteins (EcfA and EcfA'), and another transmembrane substrate-specific binding S protein (EcfS). Despite the similarities with ABC transporters, ECF transporters have different organizational and functional properties. The lack of solute-binding proteins in ECF transporters differentiates them clearly from the canonical ABC importers. Previously reported structures of the EcfS proteins RibU and ThiT clearly demonstrated the binding site of substrate riboflavin and thiamine, respectively. However, the organization of the four different components and the transport mechanism of ECF transporters remain unknown. Here we present the structure of an intact folate ECF transporter from Lactobacillus brevis at a resolution of 3 Å. This structure was captured in an inward-facing, nucleotide-free conformation with no bound substrate. The folate-binding protein FolT is nearly parallel to the membrane and is bound almost entirely by EcfT, which adopts an L shape and connects to EcfA and EcfA' through two coupling helices. Two conserved XRX motifs from the coupling helices of EcfT have a vital role in energy coupling by docking into EcfA-EcfA'. We propose a transport model that involves a

  2. Contributions of two-component regulatory systems, alternative sigma factors, and negative regulators to Listeria monocytogenes cold adaptation and cold growth.

    PubMed

    Chan, Yvonne C; Hu, Yuewei; Chaturongakul, Soraya; Files, Kali D; Bowen, Barbara M; Boor, Kathryn J; Wiedmann, Martin

    2008-02-01

    The ability of Listeria monocytogenes to grow at refrigeration temperatures is critical for transmission of this foodborne pathogen. We evaluated the contributions of different transcriptional regulators and two-component regulatory systems to L. monocytogenes cold adaptation and cold growth. L. monocytogenes parent strain 10403S and selected isogenic null mutants in genes encoding four alternative sigma factors (sigB, sigH, sigC, and sigL), two regulators of sigmaB (rsbT and rsbV), two negative regulators (ctsR and hrcA), and 15 two-component response regulators were grown in brain heart infusion broth at 4 degrees C with (i) a high-concentration starting inoculum (10(8) CFU/ml), (ii) a low-concentration starting inoculum (102 CFU/ml), and (iii) a high-concentration starting inoculum of cold-adapted cells. With a starting inoculum of 10(8) CFU/ml, null mutants in genes encoding selected alternative sigma factors (DeltasigH, DeltasigC, and DeltasigL), a negative regulator (DeltactsR), regulators of sigmaB (DeltarsbT and DeltarsbV), and selected two-component response regulators (DeltalisR, Deltalmo1172, and Deltalmo1060) had significantly reduced growth (P < 0.05) compared with the parent strain after 12 days at 4 degrees C. The growth defect for DeltasigL was limited and was not confirmed by optical density (OD600) measurement data. With a starting inoculum of 102 CFU/ml and after monitoring growth at 4 degrees C over 84 days, only the DeltactsR strain had a consistent but limited growth defect; the other mutant strains had either no growth defects or limited growth defects apparent at only one or two of the nine sampling points evaluated during the 84-day growth period (DeltasigB, DeltasigC, and Deltalmo1172). With a 10(8) CFU/ml starting inoculum of cold-adapted cells, none of the mutant strains that had a growth defect when inoculation was performed with cells pregrown at 37 degrees C had reduced growth as compared with the parent strain after 12 days at 4

  3. Role of the Extracytoplasmic Function Sigma Factor RpoE4 in Oxidative and Osmotic Stress Responses in Rhizobium etli▿ †

    PubMed Central

    Martínez-Salazar, Jaime M.; Salazar, Emmanuel; Encarnación, Sergio; Ramírez-Romero, Miguel A.; Rivera, Javier

    2009-01-01

    The aims of this study were to functionally characterize and analyze the transcriptional regulation and transcriptome of the Rhizobium etli rpoE4 gene. An R. etli rpoE4 mutant was sensitive to oxidative, saline, and osmotic stresses. Using transcriptional fusions, we determined that RpoE4 controls its own transcription and that it is negatively regulated by rseF (regulator of sigma rpoE4; CH03274), which is cotranscribed with rpoE4. rpoE4 expression was induced not only after oxidative, saline, and osmotic shocks, but also under microaerobic and stationary-phase growth conditions. The transcriptome analyses of an rpoE4 mutant and an rpoE4-overexpressing strain revealed that the RpoE4 extracytoplasmic function sigma factor regulates about 98 genes; 50 of them have the rpoE4 promoter motifs in the upstream regulatory regions. Interestingly, 16 of 38 genes upregulated in the rpoE4-overexpressing strain encode unknown putative cell envelope proteins. Other genes controlled by RpoE4 include rpoH2, CH00462, CH02434, CH03474, and xthA1, which encode proteins involved in the stress response (a heat shock sigma factor, a putative Mn-catalase, an alkylation DNA repair protein, pyridoxine phosphate oxidase, and exonuclease III, respectively), as well as several genes, such as CH01253, CH03555, and PF00247, encoding putative proteins involved in cell envelope biogenesis (a putative peptidoglycan binding protein, a cell wall degradation protein, and phospholipase D, respectively). These results suggest that rpoE4 has a relevant function in cell envelope biogenesis and that it plays a role as a general regulator in the responses to several kinds of stress. PMID:19376852

  4. 75 FR 22510 - Airworthiness Directives; Eurocopter France (ECF) Model EC120B Helicopters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ...-024-AD; Amendment 39-16265; AD 2010-05-51] RIN 2120-AA64 Airworthiness Directives; Eurocopter France... Airworthiness Directive (AD) 2010-05-51, which was sent previously to all known U.S. owners and operators of ECF... identification plate adhesive, the AD requires sanding the area until the primer coat becomes visible...

  5. 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

  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.

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

    PubMed

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

    2015-08-01

    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.

  8. 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

  9. Transcriptional control of the F0F1-ATP synthase operon of Corynebacterium glutamicum: SigmaH factor binds to its promoter and regulates its expression at different pH values

    PubMed Central

    Barriuso-Iglesias, Mónica; Barreiro, Carlos; Sola-Landa, Alberto; Martín, Juan F

    2013-01-01

    Corynebacterium glutamicum used in the amino acid fermentation industries is an alkaliphilic microorganism. Its F0F1-ATPase operon (atpBEFHAGDC) is expressed optimally at pH 9.0 forming a polycistronic (7.5 kb) and a monocistronic (1.2 kb) transcripts both starting upstream of the atpB gene. Expression of this operon is controlled by the SigmaH factor. The sigmaH gene (sigH) was cloned and shown to be co-transcribed with a small gene, cg0877, encoding a putative anti-sigma factor. A mutant deleted in the sigH gene expressed the atpBEFHAGDC operon optimally at pH 7.0 at difference of the wild-type strain (optimal expression at pH 9.0). These results suggested that the SigmaH factor is involved in pH control of expression of the F0F1 ATPase operon. The SigmaH protein was expressed in Escherichia coli fused to the GST (glutathione-S-transferase) and purified to homogeneity by affinity chromatography on a GSTrap HP column. The fused protein was identified by immunodetection with anti-GST antibodies. DNA-binding studies by electrophoretic mobility shift assays showed that the SigH protein binds to a region of the atpB promoter containing the sigmaH recognition sequence (−35)TTGGAT…18nt…GTTA(−10). SigmaH plays an important role in the cascade of control of pH stress in Corynebacterium. PMID:23298179

  10. Transcriptional control of the F0F1-ATP synthase operon of Corynebacterium glutamicum: SigmaH factor binds to its promoter and regulates its expression at different pH values.

    PubMed

    Barriuso-Iglesias, Mónica; Barreiro, Carlos; Sola-Landa, Alberto; Martín, Juan F

    2013-03-01

    Corynebacterium glutamicum used in the amino acid fermentation industries is an alkaliphilic microorganism. Its F(0)F(1)-ATPase operon (atpBEFHAGDC) is expressed optimally at pH 9.0 forming a polycistronic (7.5 kb) and a monocistronic (1.2 kb) transcripts both starting upstream of the atpB gene. Expression of this operon is controlled by the SigmaH factor. The sigmaH gene (sigH) was cloned and shown to be co-transcribed with a small gene, cg0877, encoding a putative anti-sigma factor. A mutant deleted in the sigH gene expressed the atpBEFHAGDC operon optimally at pH 7.0 at difference of the wild-type strain (optimal expression at pH 9.0). These results suggested that the SigmaH factor is involved in pH control of expression of the F(0) F(1) ATPase operon. The SigmaH protein was expressed in Escherichia coli fused to the GST (glutathione-S-transferase) and purified to homogeneity by affinity chromatography on a GSTrap HP column. The fused protein was identified by immunodetection with anti-GST antibodies. DNA-binding studies by electrophoretic mobility shift assays showed that the SigH protein binds to a region of the atpB promoter containing the sigmaH recognition sequence (-35)TTGGAT…18nt…GTTA(-10). SigmaH plays an important role in the cascade of control of pH stress in Corynebacterium.

  11. A filtrate phase perspective to organic matter balance in ECF bleached kraft fiberline.

    PubMed

    Luonsi, Antero

    2007-01-01

    In the process of making high quality pulp from wood chips, much water will continuously be needed. The fate of the used water with the organic and inorganic impurities remains optional. Mills with zero liquid effluent have been mentioned as the target in environmental loading minimization of pulp and paper mills with hardly any debate. To avoid inappropriate solutions when approaching this target, thorough knowledge of loading element behavior in liquid streams of production processes should be available before decisions are made for development alternatives. Based on empirical measurements of dissolved organic matter (DOM) in liquid streams of fiberline and utilizing them together with routine mill data in process simulation, this study aims at mapping DOM and its fate in elemental chlorine free (ECF) softwood kraft pulp production. The results of this study act as a demonstration for determining the essential fates and their quantities in the ECF fiberline.

  12. The alternative sigma factor HrpL negatively modulates the flagellar system in the phytopathogenic bacterium Erwinia amylovora under hrp-inducing conditions.

    PubMed

    Cesbron, Sophie; Paulin, Jean-Pierre; Tharaud, Michel; Barny, Marie-Anne; Brisset, Marie-Noëlle

    2006-04-01

    In this work we present evidence of an opposite regulation in the phytopathogenic bacteria Erwinia amylovora between the virulence-associated Type III secretion system (TTSS) and the flagellar system. Using loss-of-function mutants we show that motility enhanced the virulence of wild-type bacteria relative to a nonmotile mutant when sprayed on apple seedlings with unwounded leaves. Then we demonstrated through analyses of motility, flagellin export and visualization of flagellar filament that HrpL, the positive key regulator of the TTSS, also down-regulates the flagellar system. Such a dual regulation mediated by an alternative sigma factor of the TTSS appears to be a level of regulation between virulence and motility not yet described among Proteobacteria.

  13. 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.

  14. The Alternative Sigma Factor SigX Controls Bacteriocin Synthesis and Competence, the Two Quorum Sensing Regulated Traits in Streptococcus mutans

    PubMed Central

    Reck, Michael; Tomasch, Jürgen; Wagner-Döbler, Irene

    2015-01-01

    Two small quorum sensing (QS) peptides regulate competence in S. mutans in a cell density dependent manner: XIP (sigX inducing peptide) and CSP (competence stimulating peptide). Depending on the environmental conditions isogenic S. mutans cells can split into a competent and non-competent subpopulation. The origin of this population heterogeneity has not been experimentally determined and it is unknown how the two QS systems are connected. We developed a toolbox of single and dual fluorescent reporter strains and systematically knocked out key genes of the competence signaling cascade in the reporter strain backgrounds. By following signal propagation on the single cell level we discovered that the master regulator of competence, the alternative sigma factor SigX, directly controls expression of the response regulator for bacteriocin synthesis ComE. Consequently, a SigX binding motif (cin-box) was identified in the promoter region of comE. Overexpressing the genetic components involved in competence development demonstrated that ComRS represents the origin of bimodality and determines the modality of the downstream regulators SigX and ComE. Moreover these analysis showed that there is no direct regulatory link between the two QS signaling cascades. Competence is induced through a hierarchical XIP signaling cascade, which has no regulatory input from the CSP cascade. CSP exclusively regulates bacteriocin synthesis. We suggest renaming it mutacin inducing peptide (MIP). Finally, using phosphomimetic comE mutants we show that unimodal bacteriocin production is controlled posttranslationally, thus solving the puzzling observation that in complex media competence is observed in a subpopulation only, while at the same time all cells produce bacteriocins. The control of both bacteriocin synthesis and competence through the alternative sigma-factor SigX suggests that S. mutans increases its genetic repertoire via QS controlled predation on neighboring species in its

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

    PubMed

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

    2011-09-01

    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 K(33)FEHH(37)FEEC(41)SPC(44)LEK(47) that encompass the conserved HX(3)CX(2)C (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.

  16. 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.

  17. Ethanolamine Catabolism in Pseudomonas aeruginosa PAO1 Is Regulated by the Enhancer-Binding Protein EatR (PA4021) and the Alternative Sigma Factor RpoN

    PubMed Central

    Lundgren, Benjamin R.; Sarwar, Zaara; Pinto, Atahualpa; Ganley, Jack G.

    2016-01-01

    ABSTRACT Although genes encoding enzymes and proteins related to ethanolamine catabolism are widely distributed in the genomes of Pseudomonas spp., ethanolamine catabolism has received little attention among this metabolically versatile group of bacteria. In an attempt to shed light on this subject, this study focused on defining the key regulatory factors that govern the expression of the central ethanolamine catabolic pathway in Pseudomonas aeruginosa PAO1. This pathway is encoded by the PA4022-eat-eutBC operon and consists of a transport protein (Eat), an ethanolamine-ammonia lyase (EutBC), and an acetaldehyde dehydrogenase (PA4022). EutBC is an essential enzyme in ethanolamine catabolism because it hydrolyzes this amino alcohol into ammonia and acetaldehyde. The acetaldehyde intermediate is then converted into acetate in a reaction catalyzed by acetaldehyde dehydrogenase. Using a combination of growth analyses and β-galactosidase fusions, the enhancer-binding protein PA4021 and the sigma factor RpoN were shown to be positive regulators of the PA4022-eat-eutBC operon in P. aeruginosa PAO1. PA4021 and RpoN were required for growth on ethanolamine, and both of these regulatory proteins were essential for induction of the PA4022-eat-eutBC operon. Unexpectedly, the results indicate that acetaldehyde (and not ethanolamine) serves as the inducer molecule that is sensed by PA4021 and leads to the transcriptional activation of the PA4022-eat-eutBC operon. Due to its regulatory role in ethanolamine catabolism, PA4021 was given the name EatR. Both EatR and its target genes are conserved in several other Pseudomonas spp., suggesting that these bacteria share a mechanism for regulating ethanolamine catabolism. IMPORTANCE The results of this study provide a basis for understanding ethanolamine catabolism and its regulation in Pseudomonas aeruginosa PAO1. Interestingly, expression of the ethanolamine-catabolic genes in this bacterium was found to be under the control of a

  18. Six Sigma in Education

    ERIC Educational Resources Information Center

    LeMahieu, Paul G.; Nordstrum, Lee E.; Cudney, Elizabeth A.

    2017-01-01

    Purpose: This paper is one of seven in this volume that aims to elaborate different approaches to quality improvement in education. It delineates a methodology called Six Sigma. Design/methodology/approach: The paper presents the origins, theoretical foundations, core principles and a case study demonstrating an application of Six Sigma in a…

  19. 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

  20. The alternative sigma factor B modulates virulence gene expression in a murine Staphylococcus aureus infection model but does not influence kidney gene expression pattern of the host.

    PubMed

    Depke, Maren; Burian, Marc; Schäfer, Tina; Bröker, Barbara M; Ohlsen, Knut; Völker, Uwe

    2012-01-01

    Infections caused by Staphylococcus aureus are associated with significant morbidity and mortality and are an increasing threat not only in hospital settings. The expression of the staphylococcal virulence factor repertoire is known to be affected by the alternative sigma factor B (SigB). However, its impact during infection still is a matter of debate. Kidney tissues of controls or mice infected with S. aureus HG001 or its isogenic sigB mutant were analyzed by transcriptome profiling to monitor the host response, and additionally expression of selected S. aureus genes was monitored by RT-qPCR. Direct transcript analysis by RT-qPCR revealed significant SigB activity in all mice infected with the wild-type strain, but not in its isogenic sigB mutant (p<0.0001). Despite a clear-cut difference in the SigB-dependent transcription pattern of virulence genes (clfA, aur, and hla), the host reaction to infection (either wild type or sigB mutant) was almost identical. Despite its significant activity in vivo, loss of SigB did neither have an effect on the outcome of infection nor on murine kidney gene expression pattern. Thus, these data support the role of SigB as virulence modulator rather than being a virulence determinant by itself.

  1. 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.

  2. σK of Clostridium acetobutylicum is the first known sporulation-specific sigma factor with two developmentally separated roles, one early and one late in sporulation.

    PubMed

    Al-Hinai, Mohab A; Jones, Shawn W; Papoutsakis, Eleftherios T

    2014-01-01

    Sporulation in the model endospore-forming organism Bacillus subtilis proceeds via the sequential and stage-specific activation of the sporulation-specific sigma factors, σ(H) (early), σ(F), σ(E), σ(G), and σ(K) (late). Here we show that the Clostridium acetobutylicum σ(K) acts both early, prior to Spo0A expression, and late, past σ(G) activation, thus departing from the B. subtilis model. The C. acetobutylicum sigK deletion (ΔsigK) mutant was unable to sporulate, and solventogenesis, the characteristic stationary-phase phenomenon for this organism, was severely diminished. Transmission electron microscopy demonstrated that the ΔsigK mutant does not develop an asymmetric septum and produces no granulose. Complementation of sigK restored sporulation and solventogenesis to wild-type levels. Spo0A and σ(G) proteins were not detectable by Western analysis, while σ(F) protein levels were significantly reduced in the ΔsigK mutant. spo0A, sigF, sigE, sigG, spoIIE, and adhE1 transcript levels were all downregulated in the ΔsigK mutant, while those of the sigH transcript were unaffected during the exponential and transitional phases of culture. These data show that σ(K) is necessary for sporulation prior to spo0A expression. Plasmid-based expression of spo0A in the ΔsigK mutant from a nonnative promoter restored solventogenesis and the production of Spo0A, σ(F), σ(E), and σ(G), but not sporulation, which was blocked past the σ(G) stage of development, thus demonstrating that σ(K) is also necessary in late sporulation. sigK is expressed very early at low levels in exponential phase but is strongly upregulated during the middle to late stationary phase. This is the first sporulation-specific sigma factor shown to have two developmentally separated roles.

  3. Sigma-1 Receptor in Motoneuron Disease.

    PubMed

    Mancuso, Renzo; Navarro, Xavier

    2017-01-01

    Amyotrophic Lateral Sclerosis (ALS ) is a neurodegenerative disease affecting spinal cord and brain motoneurons , leading to paralysis and early death. Multiple etiopathogenic mechanisms appear to contribute in the development of ALS , including glutamate excitotoxicity, oxidative stress , protein misfolding, mitochondrial defects, impaired axonal transport, inflammation and glial cell alterations. The Sigma-1 receptor is highly expressed in motoneurons of the spinal cord, particularly enriched in the endoplasmic reticulum (ER) at postsynaptic cisternae of cholinergic C-terminals. Several evidences point to participation of Sigma-1R alterations in motoneuron degeneration. Thus, mutations of the transmembrane domain of the Sigma-1R have been described in familial ALS cases. Interestingly, Sigma-1R KO mice display muscle weakness and motoneuron loss. On the other hand, Sigma-1R agonists promote neuroprotection and neurite elongation through activation of protein kinase C on motoneurons in vitro and in vivo after ventral root avulsion. Remarkably, treatment of SOD1 mice, the most usual animal model of ALS , with Sigma-1R agonists resulted in significantly enhanced motoneuron function and preservation, and increased animal survival. Sigma-1R activation also reduced microglial reactivity and increased the glial expression of neurotrophic factors. Two main interconnected mechanisms seem to underlie the effects of Sigma-1R manipulation on motoneurons: modulation of neuronal excitability and regulation of calcium homeostasis. In addition, Sigma-1R also contributes to regulating protein degradation, and reducing oxidative stress. Therefore, the multi-functional nature of the Sigma-1R represents an attractive target for treating aspects of ALS and other motoneuron diseases .

  4. Sigma Receptor Binding Assays.

    PubMed

    Chu, Uyen B; Ruoho, Arnold E

    2015-12-08

    Sigma receptors, both Sigma-1(S1R) and Sigma-2 (S2R), are small molecule-regulated, primarily endoplasmic reticulum (ER) membrane-associated sites. A number of drugs bind to sigma receptors, including the antipsychotic haloperidol and (+)-pentazocine, an opioid analgesic. Sigma receptors are implicated in many central nervous system disorders, in particular Alzheimer's disease and conditions associated with motor control, such as Amyotrophic Lateral Sclerosis (ALS). Described in this unit are radioligand binding assays used for the pharmacological characterization of S1R and S2R. Methods detailed include a radioligand saturation binding assay for defining receptor densities and a competitive inhibition binding assay employing [³H]-(+)-pentazocine for identifying and characterizing novel ligands that interact with S1R. Procedures using [³H]-1,3-di(2-tolyl)guanidine ([³H]-DTG), a nonselective sigma receptor ligand, are described for conducting a saturation binding and competitive inhibition assays for the S2R site. These protocols are of value in drug discovery in identifying new sigma ligands and in the characterization of these receptors.

  5. 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.

  6. 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).

  7. The mycobacterial antibiotic resistance determinant WhiB7 acts as a transcriptional activator by binding the primary sigma factor SigA (RpoV)

    PubMed Central

    Burian, Ján; Yim, Grace; Hsing, Michael; Axerio-Cilies, Peter; Cherkasov, Artem; Spiegelman, George B.; Thompson, Charles J.

    2013-01-01

    Tuberculosis therapeutic options are limited by the high intrinsic antibiotic resistance of Mycobacterium tuberculosis. The putative transcriptional regulator WhiB7 is crucial for the activation of systems that provide resistance to diverse antibiotic classes. Here, we used in vitro run-off, two-hybrid assays, as well as mutagenic, complementation and protein pull-down experiments, to characterize WhiB7 as an auto-regulatory, redox-sensitive transcriptional activator in Mycobacterium smegmatis. We provide the first direct biochemical proof that a WhiB protein promotes transcription and also demonstrate that this activity is sensitive to oxidation (diamide). Its partner protein for transcriptional activation was identified as SigA, the primary sigma factor subunit of RNA polymerase. Residues required for the interaction mapped to region 4 of SigA (including R515H) or adjacent domains of WhiB7 (including E63D). WhiB7’s ability to provide a specific spectrum of antibiotic-resistance was dependent on these residues as well as its C-terminal AT-hook module that binds to an AT-rich motif immediately upstream of the −35 hexamer recognized by SigA. These experimentally established constrains, combined with protein structure predictions, were used to generate a working model of the WhiB7–SigA-promoter complex. Inhibitors preventing WhiB7 interactions could allow the use of previously ineffective antibiotics for treatment of mycobacterial diseases. PMID:23990327

  8. Sigma Factor RpoS Controls Alkylresorcinol Synthesis through ArpR, a LysR-Type Regulatory Protein, during Encystment of Azotobacter vinelandii

    PubMed Central

    Romero, Yanet; Moreno, Soledad; Guzmán, Josefina; Espín, Guadalupe

    2013-01-01

    Azotobacter vinelandii is a bacterium which undergoes a differentiation process leading to the formation of metabolically dormant cysts. During the encystment process, A. vinelandii produces alkylresorcinol lipids (ARs) that replace the membrane phospholipids and are also components of the layers covering the cyst. The synthesis of ARs in A. vinelandii has been shown to occur by the activity of enzymes encoded by the arsABCD operon, which is expressed only during the differentiation process. Also, the production of ARs has been shown to be dependent on the stationary-phase sigma factor RpoS, which is also implicated in the control of the synthesis of other cyst components (i.e., alginate and poly-β-hydroxybutyrate). In this study, we identified ArpR, a LysR-type transcriptional regulator expressed only during encystment that positively regulates arsABCD transcription. We show that this activation is dependent on acetoacetyl-coenzyme A (acetoacetyl-CoA), which might provide a metabolic signal for encystment. We also show that RpoS regulates arsABCD expression through the control of arpR transcription. PMID:23378510

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

    PubMed Central

    Guldimann, Claudia; Boor, Kathryn J.; Wiedmann, Martin

    2016-01-01

    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 σB. σB 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 σB-dependent regulation of gene expression contributes to resilience, i.e., the coordination of complex networks responsive to environmental changes. This review explores contributions of σB to resilience in Bacillus, Listeria, and Staphylococcus and illustrates recently described regulatory functions of σB. PMID:27208112

  10. 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 Central

    Houtman, Jon C.

    2016-01-01

    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

  11. The Extracytoplasmic Function Sigma Factor σS Protects against both Intracellular and Extracytoplasmic Stresses in Staphylococcus aureus

    PubMed Central

    Miller, Halie K.; Carroll, Ronan K.; Burda, Whittney N.; Krute, Christina N.; Davenport, Jessica E.

    2012-01-01

    Previously we identified a novel component of the Staphylococcus aureus regulatory network, an extracytoplasmic function σ-factor, σS, involved in stress response and disease causation. Here we present additional characterization of σS, demonstrating a role for it in protection against DNA damage, cell wall disruption, and interaction with components of the innate immune system. Promoter mapping reveals the existence of three unique sigS start sites, one of which appears to be subject to autoregulation. Transcriptional profiling revealed that sigS expression remains low in a number of S. aureus wild types but is upregulated in the highly mutated strain RN4220. Further analysis demonstrates that sigS expression is inducible upon exposure to a variety of chemical stressors that elicit DNA damage, including methyl methanesulfonate and ciprofloxacin, as well as those that disrupt cell wall stability, such as ampicillin and oxacillin. Significantly, expression of sigS is highly induced during growth in serum and upon phagocytosis by RAW 264.7 murine macrophage-like cells. Phenotypically, σS mutants display sensitivity to a broad range of DNA-damaging agents and cell wall-targeting antibiotics. Furthermore, the survivability of σS mutants is strongly impacted during challenge by components of the innate immune system. Collectively, our data suggest that σS likely serves dual functions within the S. aureus cell, protecting against both cytoplasmic and extracytoplasmic stresses. This further argues for its important, and perhaps novel, role in the S. aureus stress and virulence responses. PMID:22685284

  12. 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.

  13. Alternative sigma factors SigF, SigE, and SigG are essential for sporulation in Clostridium botulinum ATCC 3502.

    PubMed

    Kirk, David G; Zhang, Zhen; Korkeala, Hannu; Lindström, Miia

    2014-08-01

    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.

  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. Promoter Recognition by Extracytoplasmic Function σ Factors: Analyzing DNA and Protein Interaction Motifs

    PubMed Central

    Guzina, Jelena

    2016-01-01

    ABSTRACT Extracytoplasmic function (ECF) σ factors are the largest and the most diverse group of alternative σ factors, but their mechanisms of transcription are poorly studied. This subfamily is considered to exhibit a rigid promoter structure and an absence of mixing and matching; both −35 and −10 elements are considered necessary for initiating transcription. This paradigm, however, is based on very limited data, which bias the analysis of diverse ECF σ subgroups. Here we investigate DNA and protein recognition motifs involved in ECF σ factor transcription by a computational analysis of canonical ECF subfamily members, much less studied ECF σ subgroups, and the group outliers, obtained from recently sequenced bacteriophages. The analysis identifies an extended −10 element in promoters for phage ECF σ factors; a comparison with bacterial σ factors points to a putative 6-amino-acid motif just C-terminal of domain σ2, which is responsible for the interaction with the identified extension of the −10 element. Interestingly, a similar protein motif is found C-terminal of domain σ2 in canonical ECF σ factors, at a position where it is expected to interact with a conserved motif further upstream of the −10 element. Moreover, the phiEco32 ECF σ factor lacks a recognizable −35 element and σ4 domain, which we identify in a homologous phage, 7-11, indicating that the extended −10 element can compensate for the lack of −35 element interactions. Overall, the results reveal greater flexibility in promoter recognition by ECF σ factors than previously recognized and raise the possibility that mixing and matching also apply to this group, a notion that remains to be biochemically tested. IMPORTANCE ECF σ factors are the most numerous group of alternative σ factors but have been little studied. Their promoter recognition mechanisms are obscured by the large diversity within the ECF σ factor group and the limited similarity with the well

  16. Atmospheric chemistry of Z- and E-CF3CH[double bond, length as m-dash]CHCF3.

    PubMed

    Østerstrøm, Freja F; Andersen, Simone Thirstrup; Sølling, Theis I; Nielsen, Ole John; Sulbaek Andersen, Mads P

    2016-12-21

    The atmospheric fates of Z- and E-CF3CH[double bond, length as m-dash]CHCF3 have been studied, investigating the kinetics and the products of the reactions of the two compounds with Cl atoms, OH radicals, OD radicals, and O3. FTIR smog chamber experiments measured: k(Cl + Z-CF3CH[double bond, length as m-dash]CHCF3) = (2.59 ± 0.47) × 10(-11), k(Cl + E-CF3CH[double bond, length as m-dash]CHCF3) = (1.36 ± 0.27) × 10(-11), k(OH + Z-CF3CH[double bond, length as m-dash]CHCF3) = (4.21 ± 0.62) × 10(-13), k(OH + E-CF3CH[double bond, length as m-dash]CHCF3) = (1.72 ± 0.42) × 10(-13), k(OD + Z-CF3CH[double bond, length as m-dash]CHCF3) = (6.94 ± 1.25) × 10(-13), k(OD + E-CF3CH[double bond, length as m-dash]CHCF3) = (5.61 ± 0.98) × 10(-13), k(O3 + Z-CF3CH[double bond, length as m-dash]CHCF3) = (6.25 ± 0.70) × 10(-22), and k(O3 + E-CF3CH[double bond, length as m-dash]CHCF3) = (4.14 ± 0.42) × 10(-22) cm(3) molecule(-1) s(-1) in 700 Torr of air/N2/O2 diluents at 296 ± 2 K. E-CF3CH[double bond, length as m-dash]CHCF3 reacts with Cl atoms to give CF3CHClC(O)CF3 in a yield indistinguishable from 100%. Z-CF3CH[double bond, length as m-dash]CHCF3 reacts with Cl atoms to give (95 ± 10)% CF3CHClC(O)CF3 and (7 ± 1)% E-CF3CH[double bond, length as m-dash]CHCF3. CF3CHClC(O)CF3 reacts with Cl atoms to give the secondary product CF3C(O)Cl in a yield indistinguishable from 100%, with the observed co-products C(O)F2 and CF3O3CF3. The main atmospheric fate for Z- and E-CF3CH[double bond, length as m-dash]CHCF3 is reaction with OH radicals. The atmospheric lifetimes of Z- and E-CF3CH[double bond, length as m-dash]CHCF3 are estimated as 27 and 67 days, respectively. IR absorption cross sections are reported and the global warming potentials (GWPs) of Z- and E-CF3CH[double bond, length as m-dash]CHCF3 for the 100 year time horizon are calculated to be GWP100 = 2 and 7, respectively. This study provides a comprehensive description of the atmospheric fate and impact of Z- and E-CF

  17. Influence of the RpoS (KatF) sigma factor on maintenance of viability and culturability of Escherichia coli and Salmonella typhimurium in seawater.

    PubMed Central

    Munro, P M; Flatau, G N; Clément, R L; Gauthier, M J

    1995-01-01

    The sigma factor RpoS is essential for stationary-phase-specific, multiple-stress resistance. We compared the viabilities (direct viable counts) and culturabilities (colony counts) in seawater of Escherichia coli and Salmonella typhimurium strains and those in which rpoS was deleted or which were deficient in guanosine 3',5'-bispyrophosphate (ppGpp) synthesis (relA spoT). RpoS, possibly via ppGpp regulation, positively influenced the culturability of these bacteria in oligotrophic seawater. This influence closely depended, however, upon the growth state of the cells and the conditions under which they were grown prior to their transfer to seawater. The protective effect of RpoS was observed only in stationary-phase cells grown at low osmolarity. A previous exposure of cells to high osmolarity (0.5 M NaCl) also had a strong influence on the effect of RpoS on cell culturability in seawater. Both E. coli and S. typhimurium RpoS mutants lost the ability to acquire a high resistance to seawater, as observed in both logarithmic-phase and stationary-phase RpoS+ cells grown at high osmolarity. A previous growth of S. typhimurium cells under anoxic conditions also modulated the incidence of RpoS on their culturability. When grown anaerobically at high osmolarity, logarithmic-phase S. typhimurium RpoS+ cells partly lost their resistance to seawater through preadaptation to high osmolarity. When grown anaerobically at high osmolarity until stationary phase, both RpoS+ and RpoS- cells retained very high levels of both viability and culturability and then did not enter the viable but nonculturable state for over 8 days in seawater because of an RpoS-independent, unknown mechanism. PMID:7646022

  18. The Helicobacter pylori Anti-Sigma Factor FlgM Is Predominantly Cytoplasmic and Cooperates with the Flagellar Basal Body Protein FlhA ▿ †

    PubMed Central

    Rust, Melanie; Borchert, Sophie; Niehus, Eike; Kuehne, Sarah A.; Gripp, Eugenia; Bajceta, Afrodita; McMurry, Jonathan L.; Suerbaum, Sebastian; Hughes, Kelly T.; Josenhans, Christine

    2009-01-01

    Helicobacter pylori requires flagellar motility and orientation to persist actively in its habitat. A particular feature of flagella in most Helicobacter species including H. pylori is a membraneous flagellar sheath. The anti-sigma factor FlgM of H. pylori is unusual, since it lacks an N-terminal domain present in other FlgM homologs, e.g., FlgM of Salmonella spp., whose regulatory function is intimately coupled to its secretion through the flagellar type III secretion system. The aim of the present study was to characterize the localization and secretion of the short H. pylori FlgM in the presence of a flagellar sheath and to elucidate its interaction with other flagellar proteins, such as the basal body protein FlhA, which was previously shown to cooperate with FlgM for regulation. H. pylori FlgM was only released into the medium in minor amounts in wild-type bacteria, where the bulk amount of the protein was retained in the cytoplasm. Some FlgM was detected in the flagellar fraction. FlgM was expressed in flhA mutants and was less soluble and differentially localized in bacterial fractions of the flhA mutant in comparison to wild-type bacteria. FlgM-green fluorescent protein and FlgM-V5 translational fusions were generated and expressed in H. pylori. FlgM displayed a predominantly polar distribution and interacted with the C-terminal domain of FlhA (FlhAC). We suggest that, in H. pylori, FlgM secretion may not be paramount for its regulatory function and that protein interactions at the flagellar basal body may determine the turnover and localization of functional FlgM. PMID:19465658

  19. The sigma54 global regulon in Salmonella enterica serovar Typhimurium 14028s: an extensive array of intragenic sigma54 regulatory sites revealed

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An essential determinant of a transcriptional regulon is the sigma factor that associates with core RNA polymerase (E) to direct promoter-specific binding and transcription initiation by the holoenzyme (Esigma). In addition to the primary sigma factor, sigma70, S. Typhimurium has five alternative si...

  20. 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

  1. SIGMA RECEPTOR BINDING ASSAYS

    PubMed Central

    CHU, UYEN B.; RUOHO, ARNOLD E.

    2016-01-01

    Sigma receptors belong to a class of small molecule-regulated, primarily endoplasmic reticulum (ER) membrane-associated receptors, of which there are two subtypes: the Sigma-1 receptor (S1R) and the Sigma-2 receptor (S2R). Both S1R and S2R bind to a number of drugs including antipsychotic, haloperidol, and the opioid analgesic, (+)-pentazocine. Sigma receptors are implicated in multiple disease pathologies associated with the nervous system including diseases affecting motor control such as Amyotrophic Lateral Sclerosis (ALS) and Alzeimher's disease. This unit describes methods for the pharmacological characterization of S1R and S2R using radioligand-binding assays. In the first section, radioligand saturation binding assay to determine receptor densities and competitive inhibition assays to characterize affinities of novel compounds are presented for S1R using the selective S1R ligand, [3H]-(+)-pentazocine. The second section describes radioligand saturation binding assay and competitive inhibition assays for the S2R using a non-selective S1R and S2R ligand, [3H]-1,3-di(2-tolyl)guanidine ([3H]-DTG). PMID:26646191

  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. Mapping global effects of the anti-sigma factor MucA in Pseudomonas fluorescens SBW25 through genome-scale metabolic modeling

    PubMed Central

    2013-01-01

    Background Alginate is an industrially important polysaccharide, currently produced commercially by harvesting of marine brown sea-weeds. The polymer is also synthesized as an exo-polysaccharide by bacteria belonging to the genera Pseudomonas and Azotobacter, and these organisms may represent an alternative alginate source in the future. The current work describes an attempt to rationally develop a biological system tuned for very high levels of alginate production, based on a fundamental understanding of the system through metabolic modeling supported by transcriptomics studies and carefully controlled fermentations. Results Alginate biosynthesis in Pseudomonas fluorescens was studied in a genomics perspective, using an alginate over-producing strain carrying a mutation in the anti-sigma factor gene mucA. Cells were cultivated in chemostats under nitrogen limitation on fructose or glycerol as carbon sources, and cell mass, growth rate, sugar uptake, alginate and CO2 production were monitored. In addition a genome scale metabolic model was constructed and samples were collected for transcriptome analyses. The analyses show that polymer production operates in a close to optimal way with respect to stoichiometric utilization of the carbon source and that the cells increase the uptake of carbon source to compensate for the additional needs following from alginate synthesis. The transcriptome studies show that in the presence of the mucA mutation, the alg operon is upregulated together with genes involved in energy generation, genes on both sides of the succinate node of the TCA cycle and genes encoding ribosomal and other translation-related proteins. Strains expressing a functional MucA protein (no alginate production) synthesize cellular biomass in an inefficient way, apparently due to a cycle that involves oxidation of NADPH without ATP production. The results of this study indicate that the most efficient way of using a mucA mutant as a cell factory for alginate

  4. Six Sigma pricing.

    PubMed

    Sodhi, ManMohan S; Sodhi, Navdeep S

    2005-05-01

    Many companies are now good at managing costs and wringing out manufacturing efficiencies. The TQM movement and the disciplines of Six Sigma have seen to that. But the discipline so often brought to the cost side of the business equation is found far less commonly on the revenue side. The authors describe how a global manufacturer of industrial equipment, which they call Acme Incorporated, recently applied Six Sigma to one major revenue related activity--the price-setting process. It seemed to Acme's executives that pricing closely resembled many manufacturing processes. So, with the help of a Six Sigma black belt from manufacturing, a manager from Acme's pricing division recruited a team to carry out the five Six Sigma steps: Define what constitutes a defect. At Acme, a defect was an item sold at an unauthorized price. Gather data and prepare it for analysis. That involved mapping out the existing pricing-agreement process. Analyze the data. The team identified the ways in which people failed to carry out or assert effective control at each stage. Recommend modifications to the existing process. The team sought to decrease the number of unapproved prices without creating an onerous approval apparatus. Create controls. This step enabled Acme to sustain and extend the improvements in its pricing procedures. As a result of the changes, Acme earned dollar 6 million in additional revenue on one product line alone in the six months following implementation--money that went straight to the bottom line. At the same time, the company removed much of the organizational friction that had long bedeviled its pricing process. Other companies can benefit from Acme's experience as they look for ways to exercise price control without alienating customers.

  5. Transcriptomic and phenotypic characterization of a Bacillus subtilis strain without extracytoplasmic function σ factors.

    PubMed

    Luo, Yun; Asai, Kei; Sadaie, Yoshito; Helmann, John D

    2010-11-01

    Bacillus subtilis encodes seven extracytoplasmic function (ECF) σ factors. Three (σ(M), σ(W), and σ(X)) mediate responses to cell envelope-active antibiotics. The functions of σ(V), σ(Y), σ(Z), and σ(YlaC) remain largely unknown, and strong inducers of these σ factors and their regulons have yet to be defined. Here, we define transcriptomic and phenotypic differences under nonstress conditions between a strain carrying deletions in all seven ECF σ factor genes (the Δ7ECF mutant), a ΔMWX triple mutant, and the parental 168 strain. Our results identify >80 genes as at least partially dependent on ECF σ factors, and as expected, most of these are dependent on σ(M), σ(W), or σ(X), which are active at a significant basal level during growth. Several genes, including the eps operon encoding enzymes for exopolysaccharide (EPS) production, were decreased in expression in the Δ7ECF mutant but affected less in the ΔMWX mutant. Consistent with this observation, the Δ7ECF mutant (but not the ΔMWX mutant) showed reduced biofilm formation. Extending previous observations, we also note that the ΔMWX mutant is sensitive to a variety of antibiotics and the Δ7ECF mutant is either as sensitive as, or slightly more sensitive than, the ΔMWX strain to these stressors. These findings emphasize the overlapping nature of the seven ECF σ factor regulons in B. subtilis, confirm that three of these (σ(M), σ(W), and σ(X)) play the dominant role in conferring intrinsic resistance to antibiotics, and provide initial insights into the roles of the remaining ECF σ factors.

  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. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. Osmotolerance provided by the alternative sigma factors σB and rpoS to Staphylococcus aureus and Escherichia coli is solute dependent and does not result in an increased growth fitness in NaCl containing media.

    PubMed

    Cebrián, G; Arroyo, C; Condón, S; Mañas, P

    2015-12-02

    The aim of this work was to examine the role of the alternative general stress sigma factors σ(B) and rpoS on the ability of Staphylococcus aureus and Escherichia coli, respectively, to grow in liquid and solid media of different osmolarity. For this purpose, S. aureus strain Newman and its isogenic ΔsigB mutant IK84 and E. coli strain BJ4 and its isogenic ΔrpoS mutant BJ4L1 were grown in media (TSBYE) with different concentrations of NaCl. Growth parameters (lag phase duration, growth rate and maximum number of microorganisms) and limiting growth concentrations (Maximum Non-Inhibitory Concentration - MNIC - and Minimum Inhibitory Concentration - MIC-) were determined. The mechanisms underlying the differences observed between parental and mutant strains were also explored. The absence of the sigma factors σ(B) and rpoS led to a decrease in the MNICs and MICs calculated for S. aureus and E. coli, respectively. Conversely, neither σ(B) nor rpoS provided with increased growth fitness to S. aureus and E. coli cells at NaCl concentrations up to 1.36M and 1M, respectively. The decreased osmotolerance of the σ(B) and rpoS deficient strains, as compared to their parental strains, was compensated by the addition of glycine-betaine (1mM) to the growth medium. It was also observed that the decreased tolerance to NaCl of the mutant strains was coincident with a decreased tolerance to sucrose, KCl, and LiCl but not to glycerol, MgCl2, and CaCl2. Results obtained also demonstrate that the increased osmotolerance of stationary growth phase E. coli cells, as compared to exponential growth phase ones, would be due to the activation of both rpoS-independent and rpoS-dependent mechanisms. This work will help to understand the mechanisms of bacterial resistance to osmotic stress and the role of the alternative sigma factors σ(B) and rpoS in this process.

  13. Evaluation of normalization reference genes for RT-qPCR analysis of spo0A and four sporulation sigma factor genes in Clostridium botulinum Group I strain ATCC 3502.

    PubMed

    Kirk, David G; Palonen, Eveliina; Korkeala, Hannu; Lindström, Miia

    2014-04-01

    Heat-resistant spores of Clostridium botulinum can withstand the pasteurization processes in modern food processing. This poses a risk to food safety as spores may germinate into botulinum neurotoxin-producing vegetative cells. Sporulation in Bacillus subtilis, the model organism for sporulation, is regulated by the transcription factor Spo0A and four alternative sigma factors, SigF, SigE, SigG, and SigK. While the corresponding regulators are found in available genomes of C. botulinum, little is known about their expression. To accurately measure the expression of these genes using quantitative reverse-transcriptase PCR (RT-qPCR) during the exponential and stationary growth phases, a suitable normalization reference gene is required. 16S rrn, adK, alaS, era, gluD, gyrA, rpoC, and rpsJ were selected as the candidate reference genes. The most stable candidate reference gene was 16S ribosomal RNA gene (rrn), based on its low coefficient of variation (1.81%) measured during the 18-h study time. Using 16S rrn as the normalization reference gene, the relative expression levels of spo0A, sigF, sigE, sigG, and sigK were measured over 18h. The pattern of expression showed spo0A expression during the logarithmic growth phase, followed by a drop in expression upon entry to the stationary phase. Expression levels of sigF, sigE, and sigG peaked simultaneously at the end of the exponential growth phase. Peak expression of sigK occurred at 18h, however low levels of expression were detected during the exponential phase. These findings suggest these sigma factors play a role in C. botulinum sporulation that is similar, but not equal, to their role in the B. subtilis model.

  14. Cloning, sequencing, and disruption of the Bacillus subtilis sigma 28 gene.

    PubMed Central

    Helmann, J D; Márquez, L M; Chamberlin, M J

    1988-01-01

    Bacillus subtilis contains multiple forms of RNA polymerase holoenzyme, distinguished by the presence of different specificity determinants known as sigma factors. The sigma 28 factor was initially purified as a unique transcriptional activity in vegetatively growing B. subtilis cells. Purification of the sigma 28 protein has allowed tryptic peptides to be prepared and sequenced. The sequence of one tryptic peptide fragment was used to prepare an oligonucleotide probe specific for the sigma 28 structural gene, and the gene was isolated from a B. subtilis subgenomic library. The complete nucleotide sequence of the sigma 28 gene was determined, and the cloned sigma 28 gene was used to construct a mutant strain which does not express the sigma 28 protein. This strain also failed to synthesize flagellin protein and grew as long filaments. The predicted sigma 28 gene product is a 254-amino-acid polypeptide with a calculated molecular weight of 29,500. The sigma 28 protein sequence was similar to that of other sequenced sigma factors and to the flbB gene product of Escherichia coli. Since the flbB gene product is a positive regulator of flagellar synthesis in E. coli, it is likely that sigma 28 functions to regulate flagellar synthesis in B. subtilis. Images PMID:2832368

  15. Six sigma for revenue retrieval.

    PubMed

    Plonien, Cynthia

    2013-01-01

    Deficiencies in revenue retrieval due to failures in obtaining charges have contributed to a negative bottom line for numerous hospitals. Improving documentation practices through a Six Sigma process improvement initiative can minimize opportunities for errors through reviews and instill structure for compliance and consistency. Commitment to the Six Sigma principles with continuous monitoring of outcomes and constant communication of results to departments, management, and payers is a strong approach to reducing the financial impact of denials on an organization's revenues and expenses. Using Six Sigma tools can help improve the organization's financial performance not only for today, but also for health care's uncertain future.

  16. Suppression of abnormal morphology and extracytoplasmic function sigma activity in Bacillus subtilis ugtP mutant cells by expression of heterologous glucolipid synthases from Acholeplasma laidlawii.

    PubMed

    Matsuoka, Satoshi; Seki, Takahiro; Matsumoto, Kouji; Hara, Hiroshi

    2016-12-01

    Glucolipids in Bacillus subtilis are synthesized by UgtP processively transferring glucose from UDP-glucose to diacylglycerol. Here we conclude that the abnormal morphology of a ugtP mutant is caused by lack of glucolipids, since the same morphology arises after abolition of glucolipid production by disruption of pgcA and gtaB, which are involved in UDP-glucose synthesis. Conversely, expression of a monoglucosyldiacylglycerol (MGlcDG) produced by 1,2-diacylglycerol 3-glucosyltransferase from Acholeplasma laidlawii (alMGS) almost completely suppressed the ugtP disruptant phenotype. Activation of extracytoplasmic function (ECF) sigmas (SigM, SigV, and SigX) in the ugtP mutant was decreased by alMGS expression, and was suppressed to low levels by MgSO4 addition. When alMGS and alDGS (A. laidlawii 1,2-diacylglycerol-3-glucose (1-2)-glucosyltransferase producing diglucosyldiacylglycerol (DGlcDG)) were simultaneously expressed, SigX activation was repressed to wild type level. These observations suggest that MGlcDG molecules are required for maintenance of B. subtilis cell shape and regulation of ECF sigmas, and DGlcDG regulates SigX activity.

  17. BotR/A and TetR are alternative RNA polymerase sigma factors controlling the expression of the neurotoxin and associated protein genes in Clostridium botulinum type A and Clostridium tetani.

    PubMed

    Raffestin, Stéphanie; Dupuy, Bruno; Marvaud, Jean Christophe; Popoff, Michel R

    2005-01-01

    Clostridium botulinum and Clostridium tetani, respectively, produce potent toxins, botulinum neurotoxin (BoNT) and tetanus neurotoxin (TeTx), which are responsible for severe diseases, botulism and tetanus. Neurotoxin synthesis is a regulated process in Clostridium. The genes botR/A in C. botulinum A and tetR in C. tetani positively regulate expression of BoNT/A and associated non-toxic proteins (ANTPs), as well as TeTx respectively. The botR/A gene lies in close vicinity of the two operons which contain bont/A and antps genes in C. botulinum A, and tetR immediately precedes the tetX gene in C. tetani. We show that BotR/A and TetR function as specific alternative sigma factors rather than positive regulators based on the following results: (i) BotR/A and TetR associated with target DNAs only in the presence of the RNA polymerase core enzyme (Core), (ii) BotR/A and TetR directly bound with the core enzyme, (iii) BotR/A-Core recognized -35 and -10 regions of ntnh-bont/A promoter and (iv) BotR/A and TetR triggered in vitro transcription from the target promoters. In C. botulinum A, bont/A and antps genes are transcribed as bi- and tricistronic operons controlled by BotR/A. BotR/A and TetR are seemingly related to a new subgroup of the sigma70 family that includes TcdR and UviA, which, respectively, regulate production of toxins A and B in C. difficile and bacteriocin in C. perfringens. Sequences of -35 region are highly conserved in the promoter of target toxin genes in C. botulinum, C. tetani, C. difficile and C. perfringens. Overall, a common regulation mechanism probably controls toxin gene expression in these four toxigenic clostridial species.

  18. Characterization of four nuclear-encoded plastid RNA polymerase sigma factor genes in the liverwort Marchantia polymorpha: blue-light- and multiple stress-responsive SIG5 was acquired early in the emergence of terrestrial plants.

    PubMed

    Kanazawa, Takehiko; Ishizaki, Kimitsune; Kohchi, Takayuki; Hanaoka, Mitsumasa; Tanaka, Kan

    2013-10-01

    The plastids of plant cells each contain their own genome, and a bacterial-type RNA polymerase called plastid-encoded plastid RNA polymerase (PEP) is involved in transcription of this genome. While the catalytic core subunits are encoded by the plastid genome, the specificity subunit of PEP, sigma, is generally encoded by the nuclear genome and imported into plastids from the cytoplasm after translation. In this study, we identified and analyzed four sigma factor genes from the nuclear genome of a liverwort, Marchantia polymorpha. Phylogenetic analysis suggested that three of the four genes were orthologous to vascular plant genes and thus they were named MpSIG1, MpSIG2 and MpSIG5. The remaining gene was named MpSIGX. The gene products were predicted to localize to the plastid, and this prediction was experimentally demonstrated by expressing yellow fluorescent protein fusion genes in vivo. As with SIG5 genes of other plant species, expression of MpSIG5 was induced by blue-light irradiation and also under various stress conditions, indicating that the regulatory mechanism responsible is conserved among divergent plant species. However, while the major role of SIG5 in vascular plants is to repair the damaged PSII reaction center through psbD gene transcription, the relevant blue-light-responsive promoter (psbD-BLRP) was not found in M. polymorpha and psbD transcript accumulation did not occur in conjunction with MpSIG5 induction. Thus, the physiological role of SIG5 is probably divergent among plant phyla.

  19. 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…

  20. Insights into the extracytoplasmic stress response of Xanthomonas campestris pv. campestris: role and regulation of {sigma}E-dependent activity.

    PubMed

    Bordes, Patricia; Lavatine, Laure; Phok, Kounthéa; Barriot, Roland; Boulanger, Alice; Castanié-Cornet, Marie-Pierre; Déjean, Guillaume; Lauber, Emmanuelle; Becker, Anke; Arlat, Matthieu; Gutierrez, Claude

    2011-01-01

    Xanthomonas campestris pv. campestris is an epiphytic bacterium that can become a vascular pathogen responsible for black rot disease of crucifers. To adapt gene expression in response to ever-changing habitats, phytopathogenic bacteria have evolved signal transduction regulatory pathways, such as extracytoplasmic function (ECF) σ factors. The alternative sigma factor σ(E), encoded by rpoE, is crucial for envelope stress response and plays a role in the pathogenicity of many bacterial species. Here, we combine different approaches to investigate the role and mechanism of σ(E)-dependent activation in X. campestris pv. campestris. We show that the rpoE gene is organized as a single transcription unit with the anti-σ gene rseA and the protease gene mucD and that rpoE transcription is autoregulated. rseA and mucD transcription is also controlled by a highly conserved σ(E)-dependent promoter within the σ(E) gene sequence. The σ(E)-mediated stress response is required for stationary-phase survival, resistance to cadmium, and adaptation to membrane-perturbing stresses (elevated temperature and ethanol). Using microarray technology, we started to define the σ(E) regulon of X. campestris pv. campestris. These genes encode proteins belonging to different classes, including periplasmic or membrane proteins, biosynthetic enzymes, classical heat shock proteins, and the heat stress σ factor σ(H). The consensus sequence for the predicted σ(E)-regulated promoter elements is GGAACTN(15-17)GTCNNA. Determination of the rpoH transcription start site revealed that rpoH was directly regulated by σ(E) under both normal and heat stress conditions. Finally, σ(E) activity is regulated by the putative regulated intramembrane proteolysis (RIP) proteases RseP and DegS, as previously described in many other bacteria. However, our data suggest that RseP and DegS are not only dedicated to RseA cleavage and that the proteolytic cascade of RseA could involve other proteases.

  1. A perspective on the new mechanism of antidepressants: neuritogenesis through sigma-1 receptors.

    PubMed

    Takebayashi, M; Hayashi, T; Su, T-P

    2004-11-01

    Sigma receptors were first described as one of the opiate receptor subtypes. Now it is well established that sigma receptors, existing as subtypes sigma-1 and sigma-2, are unique non-opioid receptors which are implicated in higher-ordered brain functions. Sigma-1 receptors have high to moderate affinities for (+)benzomorphans and also many psychotrophic drugs and neurosteroids. Sigma-1 receptor agonists and certain neurosteroids such as dehydroepiandrosterone sulfate (DHEA-S) have antidepressant-like effects in animal behavioral models of depression. The antidepressant-like effect induced by sigma-1 receptor agonists may involve intracellular Ca (2+) mobilization such that sigma-1 receptor agonists modulate Ca (2+) release from endoplasmic reticulum (ER) in a cytoskeletal protein-dependent manner. In addition, growth factor-induced neurite outgrowth is mediated through sigma-1 receptors, suggesting a role of antidepressants in neuroplasticity. Igmesine (JO1783), OPC-14 523 and SA4503, have recently been developed as sigma-1 agonists and are found to have antidepressant-like activity perhaps with fewer side effects. This article reviews the new potential use of sigma-1 receptor ligands in the treatment of mood disorder.

  2. Role of general stress-response alternative sigma factors σ(S) (RpoS) and σ(B) (SigB) in bacterial heat resistance as a function of treatment medium pH.

    PubMed

    Ait-Ouazzou, A; Mañas, P; Condón, S; Pagán, R; García-Gonzalo, D

    2012-02-15

    This investigation aimed to determine the role of general stress-response alternative sigma factors σ(S) (RpoS) and σ(B) (SigB) in heat resistance and the occurrence of sublethal injuries in cell envelopes of stationary-phase Escherichia coli BJ4 and Listeria monocytogenes EGD-e cells, respectively, as a function of treatment medium pH. Given that microbial death followed first-order inactivation kinetics (R(2)>0.95) the traditional D(T) and z values were used to describe the heat inactivation kinetics. Influence of rpoS deletion was constant at every treatment temperature and pH, making a ΔrpoS deletion mutant strain approximately 5.5 times more heat sensitive than its parental strain for every studied condition. Furthermore, the influence of the pH of the treatment medium on the reduction of the heat resistance of E. coli was also constant and independent of the treatment temperature (average z value=4.9°C) in both parental and mutant strains. L. monocytogenes EGD-e z values obtained at pH 7.0 and 5.5 were not significantly different (p>0.05) in either parental or the ∆sigB deletion mutant strains (average z value=4.8°C). Nevertheless, at pH 4.0 the z value was higher (z=8.4°C), indicating that heat resistance of both L. monocytogenes strains was less dependent on temperature at pH 4.0. At both pH 5.5 and 7.0 the influence of sigB deletion was constant and independent of the treatment temperature, decreasing L. monocytogenes heat resistance approximately 2.5 times. In contrast, the absence of sigB did not decrease the heat resistance of L. monocytogenes at pH 4.0. The role of RpoS in protecting cell envelopes was more important in E. coli (4 times) than SigB in L. monocytogenes (1.5 times). Moreover, the role of σ(S) in increasing heat resistance seems more relevant in enhancing the intrinsic resilience of the cytoplasmic membrane, and to a lesser extent, outer membrane resilience. Knowledge of environmental conditions related to the activation of

  3. The Escherichia coli regulator of sigma 70 protein, Rsd, can up-regulate some stress-dependent promoters by sequestering sigma 70.

    PubMed

    Mitchell, Jennie E; Oshima, Taku; Piper, Sarah E; Webster, Christine L; Westblade, Lars F; Karimova, Gouzel; Ladant, Daniel; Kolb, Annie; Hobman, Jon L; Busby, Stephen J W; Lee, David J

    2007-05-01

    The Escherichia coli Rsd protein forms complexes with the RNA polymerase sigma(70) factor, but its biological role is not understood. Transcriptome analysis shows that overexpression of Rsd causes increased expression from some promoters whose expression depends on the alternative sigma(38) factor, and this was confirmed by experiments with lac fusions at selected promoters. The LP18 substitution in Rsd increases the Rsd-dependent stimulation of these promoter-lac fusions. Analysis with a bacterial two-hybrid system shows that the LP18 substitution in Rsd increases its interaction with sigma(70). Our experiments support a model in which the role of Rsd is primarily to sequester sigma(70), thereby increasing the levels of RNA polymerase containing the alternative sigma(38) factor.

  4. Dirac sigma models from gauging

    NASA Astrophysics Data System (ADS)

    Salnikov, Vladimir; Strobl, Thomas

    2013-11-01

    The G/G WZW model results from the WZW-model by a standard procedure of gauging. G/G WZW models are members of Dirac sigma models, which also contain twisted Poisson sigma models as other examples. We show how the general class of Dirac sigma models can be obtained from a gauging procedure adapted to Lie algebroids in the form of an equivariantly closed extension. The rigid gauge groups are generically infinite dimensional and a standard gauging procedure would give a likewise infinite number of 1-form gauge fields; the proposed construction yields the requested finite number of them. Although physics terminology is used, the presentation is kept accessible also for a mathematical audience.

  5. Sigma-1 Receptors and Neurodegenerative Diseases: Towards a Hypothesis of Sigma-1 Receptors as Amplifiers of Neurodegeneration and Neuroprotection.

    PubMed

    Nguyen, Linda; Lucke-Wold, Brandon P; Mookerjee, Shona; Kaushal, Nidhi; Matsumoto, Rae R

    2017-01-01

    Sigma-1 receptors are molecular chaperones that may act as pathological mediators and targets for novel therapeutic applications in neurodegenerative diseases. Accumulating evidence indicates that sigma-1 ligands can either directly or indirectly modulate multiple neurodegenerative processes, including excitotoxicity, calcium dysregulation, mitochondrial and endoplasmic reticulum dysfunction, inflammation, and astrogliosis. In addition, sigma-1 ligands may act as disease-modifying agents in the treatment for central nervous system (CNS) diseases by promoting the activity of neurotrophic factors and neural plasticity. Here, we summarize their neuroprotective and neurorestorative effects in different animal models of acute brain injury and chronic neurodegenerative diseases, and highlight their potential role in mitigating disease. Notably, current data suggest that sigma-1 receptor dysfunction worsens disease progression, whereas enhancement amplifies pre-existing functional mechanisms of neuroprotection and/or restoration to slow disease progression. Collectively, the data support a model of the sigma-1 receptor as an amplifier of intracellular signaling, and suggest future clinical applications of sigma-1 ligands as part of multi-therapy approaches to treat neurodegenerative diseases.

  6. The metabolism of (R)-3-hydroxybutyrate is regulated by the enhancer-binding protein PA2005 and the alternative sigma factor RpoN in Pseudomonas aeruginosa PAO1.

    PubMed

    Lundgren, Benjamin R; Harris, Joshua R; Sarwar, Zaara; Scheel, Ryan A; Nomura, Christopher T

    2015-11-01

    A variety of soil-dwelling bacteria produce polyhydroxybutyrate (PHB), which serves as a source of energy and carbon under nutrient deprivation. Bacteria belonging to the genus Pseudomonas do not generally produce PHB but are capable of using the PHB degradation product (R)-3-hydroxybutyrate [(R)-3-HB] as a growth substrate. Essential to this utilization is the NAD+-dependent dehydrogenase BdhA that converts (R)-3-HB into acetoacetate, a molecule that readily enters central metabolism. Apart from the numerous studies that had focused on the biochemical characterization of BdhA, there was nothing known about the assimilation of (R)-3-HB in Pseudomonas, including the genetic regulation of bdhA expression. This study aimed to define the regulatory factors that govern or dictate the expression of the bdhA gene and (R)-3-HB assimilation in Pseudomonas aeruginosa PAO1. Importantly, expression of the bdhA gene was found to be specifically induced by (R)-3-HB in a manner dependent on the alternative sigma factor RpoN and the enhancer-binding protein PA2005.This mode of regulation was essential for the utilization of (R)-3-HB as a sole source of energy and carbon. However, non-induced levels of bdhA expression were sufficient for P. aeruginosa PAO1 to grow on ( ± )-1,3-butanediol, which is catabolized through an (R)-3-HB intermediate. Because this is, we believe, the first report of an enhancer-binding protein that responds to (R)-3-HB, PA2005 was named HbcR for (R)-3-hydroxybutyrate catabolism regulator.

  7. The metabolism of (R)-3-hydroxybutyrate is regulated by the enhancer-binding protein PA2005 and the alternative sigma factor RpoN in Pseudomonas aeruginosa PAO1

    PubMed Central

    Lundgren, Benjamin R.; Harris, Joshua R.; Sarwar, Zaara; Scheel, Ryan A.

    2015-01-01

    A variety of soil-dwelling bacteria produce polyhydroxybutyrate (PHB), which serves as a source of energy and carbon under nutrient deprivation. Bacteria belonging to the genus Pseudomonas do not generally produce PHB but are capable of using the PHB degradation product (R)-3-hydroxybutyrate [(R)-3-HB] as a growth substrate. Essential to this utilization is the NAD+-dependent dehydrogenase BdhA that converts (R)-3-HB into acetoacetate, a molecule that readily enters central metabolism. Apart from the numerous studies that had focused on the biochemical characterization of BdhA, there was nothing known about the assimilation of (R)-3-HB in Pseudomonas, including the genetic regulation of bdhA expression. This study aimed to define the regulatory factors that govern or dictate the expression of the bdhA gene and (R)-3-HB assimilation in Pseudomonas aeruginosa PAO1. Importantly, expression of the bdhA gene was found to be specifically induced by (R)-3-HB in a manner dependent on the alternative sigma factor RpoN and the enhancer-binding protein PA2005.This mode of regulation was essential for the utilization of (R)-3-HB as a sole source of energy and carbon. However, non-induced levels of bdhA expression were sufficient for P. aeruginosa PAO1 to grow on ( ± )-1,3-butanediol, which is catabolized through an (R)-3-HB intermediate. Because this is, we believe, the first report of an enhancer-binding protein that responds to (R)-3-HB, PA2005 was named HbcR for (R)-3-hydroxybutyrate catabolism regulator. PMID:26311173

  8. 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.

  9. Structure-function studies of Escherichia coli RpoH (sigma32) by in vitro linker insertion mutagenesis.

    PubMed

    Narberhaus, Franz; Balsiger, Sylvia

    2003-05-01

    The sigma factor RpoH (sigma(32)) is the key regulator of the heat shock response in Escherichia coli. Many structural and functional properties of the sigma factor are poorly understood. To gain further insight into RpoH regions that are either important or dispensable for its cellular activity, we generated a collection of tetrapeptide insertion variants by a recently established in vitro linker insertion mutagenesis technique. Thirty-one distinct insertions were obtained, and their sigma factor activity was analyzed by using a groE-lacZ reporter fusion in an rpoH-negative background. Our study provides a map of permissive sites which tolerate linker insertions and of functionally important regions at which a linker insertion impairs sigma factor activity. Selected linker insertion mutants will be discussed in the light of known sigma factor properties and in relation to a modeled structure of an RpoH fragment containing region 2.

  10. 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.

  11. Topological sigma models on supermanifolds

    NASA Astrophysics Data System (ADS)

    Jia, Bei

    2017-02-01

    This paper concerns constructing topological sigma models governing maps from semirigid super Riemann surfaces to general target supermanifolds. We define both the A model and B model in this general setup by defining suitable BRST operators and physical observables. Using supersymmetric localization, we express correlation functions in these theories as integrals over suitable supermanifolds. In the case of the A model, we obtain an integral over the supermoduli space of "superinstantons". The language of supergeometry is used extensively throughout this paper.

  12. Branes in Poisson sigma models

    SciTech Connect

    Falceto, Fernando

    2010-07-28

    In this review we discuss possible boundary conditions (branes) for the Poisson sigma model. We show how to carry out the perturbative quantization in the presence of a general pre-Poisson brane and how this is related to the deformation quantization of Poisson structures. We conclude with an open problem: the perturbative quantization of the system when the boundary has several connected components and we use a different pre-Poisson brane in every component.

  13. 75 FR 38956 - Airworthiness Directives; Eurocopter France (ECF) Model SA330F, G, and J; and AS332C, L, L1, and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-07

    ... (ECF) Model SA330F, G, and J; and AS332C, L, L1, and L2 Helicopters AGENCY: Federal Aviation... for the SA330F, G, and J helicopters, and 52.00.38 for the AS332C, C1, L, L1, and L2 helicopters, both... (b) None. Applicability (c) This AD applies to Model SA330F, G, J, and AS332C, L, L1, and...

  14. 75 FR 70104 - Airworthiness Directives; Eurocopter France (ECF) Model SA330F, G, and J; and AS332C, L, L1, and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-17

    ... (ECF) Model SA330F, G, and J; and AS332C, L, L1, and L2 Helicopters AGENCY: Federal Aviation... for the SA330F, G, and J helicopters, and 52.00.38 for the AS332C, C1, L, L1, and L2 helicopters, both... applies to Model SA330F, G, J, and AS332C, L, L1, and L2 helicopters, certificated in any category....

  15. Summary of best practice recommendations for management of enterocutaneous fistulae from the Canadian Association for Enterostomal Therapy ECF Best Practice Recommendations Panel.

    PubMed

    McNaughton, Virginia; Brown, Jean; Hoeflok, Jo; Martins, Lina; McNaughton, Virginia; Nielsen, Elise M; Thompson, Gail; Westendorp, Claire

    2010-01-01

    These recommendations are a comprehensive resource summarizing the current literature that supports the care of the person with an enterocutaneous fistula (ECF). They are the result of the decision of the Canadian Association for Enterostomal Therapy to provide an open-source guide to clinicians in the care of the person with ECF. It is intended as a tool for nurses to assist in decision making and priority setting when developing individualized care plans. It is not intended to be a clinical practice guideline but, like its progenitor the Canadian Association for Wound Care: Best Practice Recommendations for Wound Care, it is a distillation of existing research, expert opinion, and case studies intended to enable clinicians to determine their clinical practice based on the best available evidence. It is a living document and as such it is expected that having identified the gaps in knowledge and practice, clinicians will begin the research and publications necessary to fill in these gaps. Contributions to this body of knowledge are essential to an evolving improvement in care for patients living with ECF.

  16. The expression and functional characterization of sigma (sigma) 1 receptors in breast cancer cell lines.

    PubMed

    Aydar, Ebru; Onganer, Pinar; Perrett, Rebecca; Djamgoz, Mustafa B; Palmer, Christopher P

    2006-10-28

    Sigma (sigma) receptors have been implicated in cancer. However, to date there is little molecular data demonstrating the role of sigma1 receptors in cancer. Expression of sigma1 receptors in various human cancer cell lines in comparison to non-cancerous cell lines was investigated, using real time RT-PCR and by western blotting with a sigma1 receptor specific antibody. Our results indicate that cancer cells express higher levels of sigma1 receptors than corresponding non-cancerous cells. Localization of the sigma1 receptor was investigated in MDA-MB-231 cells by immunocytochemistry and confocal microscopy, expression was visualized predominantly at the cell periphery. We have tested the effect of sigma1 and sigma2 drugs and a sigma1 receptor silencing construct on various aspects of the metastatic process on two breast cell lines of different metastatic potential and a normal breast cell line. Both sigma1 and sigma2 drugs and the sigma1 receptor silencing construct had effects on proliferation and adhesion for breast cancer cell lines, compared to a non-cancerous breast cell line. This data suggests sigma1 receptor plays a role in proliferation and adhesion of breast cancer cells. Therefore, it is likely to be a potential target for the diagnosis and therapy of breast cancer.

  17. An update on the development of drugs for neuropsychiatric disorders: focusing on the sigma 1 receptor ligand.

    PubMed

    Hayashi, Teruo; Su, Tsung-Ping

    2008-01-01

    The sigma1 receptor is an intracellular molecule that shares no homology with any mammalian proteins. sigma1 receptors normally localize at the endoplasmic reticulum and regulate a variety of signal transductions including intracellular Ca2+ dynamics and neurotrophic factor signaling. In the brain, sigma1 receptors are known to regulate the activity of diverse ion channels via protein-protein interactions. Accumulated evidences strongly indicate that the activation/upregulation of sigma1 receptors promotes the neuronal differentiation as well as a robust antiapoptotic action. In animals, sigma1 receptor agonists exhibit an antidepressant-like action. Furthermore, the agonists enhanced neuronal survival eventhough they were administered several hours after a brain ischemia. Thus, primary clinical targets of sigma1 receptor ligands are proposed to include stroke, neurodegenerative disorders and depression. Ligands for the sigma1 receptor may constitute a new class of therapeutic drugs targeting an endoplasmic reticular protein.

  18. Imaging sigma receptors: applications in drug development.

    PubMed

    Collier, Thomas Lee; Waterhouse, Rikki N; Kassiou, Michael

    2007-01-01

    Sigma receptors have been implicated in a myriad of cellular functions, biological processes and diseases. While the precise biological functions of sigma receptors have not been elucidated, recent work has shed some light on to these enigmatic systems. Sigma receptors have recently been a target of drug development related to psychiatric and neurological disorders. Sigma ligands have also been shown to modulate endothelial cell proliferation and can control angiogenesis which makes them a promising target for oncology applications. Other areas currently being investigated include treatment of gastrointestinal, cardiovascular, endocrine and immune system disorders. Of interest is that the human sigma-1 receptor gene contains a steroid binding component, and several gonadal steroids, including progesterone, testosterone and dehydroepiandrosterone (DHEA), interact with sigma-1 receptors. Of the steroids examined thus far, progesterone binds with the highest affinity to human sigma-1 receptors, with a reported affinity (Ki) as high as 30 nM while the other steroids exhibit lower affinity. For this and other reasons, sigma-1 receptors have been proposed as a link between the central nervous system and the endocrine and reproductive systems. Taken together, the above information highlights an important yet largely unexplored but promising area of research to examine the biological function and therapeutic potential of sigma receptors. This review provides an overview of the current knowledge of these sites with a focus on specific areas where in vivo sigma receptor imaging is currently being investigated.

  19. 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...

  20. Sigma-1 receptor agonists as therapeutic drugs for cognitive impairment in neuropsychiatric diseases.

    PubMed

    Niitsu, Tomihisa; Iyo, Masaomi; Hashimoto, Kenji

    2012-01-01

    Cognitive impairment is a core feature of patients with neuropsychiatric diseases such as schizophrenia and psychotic depression. The drugs currently used to treat cognitive impairment have significant limitations, ensuring that the search for more effective therapies remains active. Endoplasmic reticulum protein sigma-1 receptors are unique binding sites in the brain that exert a potent effect on multiple neurotransmitter systems. Accumulating evidence suggests that sigma-1 receptors play a role in both the pathophysiology of neuropsychiatric diseases, and the mechanistic action of some therapeutic drugs, such as the selective serotonin reuptake inhibitors (SSRIs), donepezil and neurosteroids. Among SSRIs, fluvoxamine, a potent sigma-1 receptor agonist, has the highest affinity at sigma-1 receptors. Sigma-1 receptor agonists greatly potentiate nerve-growth factor (NGF)-induced neurite outgrowth in PC12 cells, an effect that is antagonized by treatment with the selective sigma-1 receptor antagonist NE-100. Furthermore, phencyclidine (PCP)-induced cognitive impairment, associated with animal models of schizophrenia is significantly improved by sub-chronic administration of sigma-1 receptor agonists such as fluvoxamine, SA4503 (cutamesine) and donepezil. This effect is antagonized by co-administration of NE-100. A positron emission tomography (PET) study using the specific sigma-1 receptor ligand [11C]SA4503 demonstrates that fluvoxamine and donepezil bind to sigma-1 receptors in the healthy human brain. In clinical studies, some sigma-1 receptor agonists, including fluvoxamine, donepezil and neurosteroids, improve cognitive impairment and clinical symptoms in neuropsychiatric diseases. In this article, we review the recent findings on sigma-1 receptor agonists as potential therapeutic drugs for the treatment of cognitive impairment in schizophrenia and psychotic depression.

  1. Applying Sigma Metrics to Reduce Outliers.

    PubMed

    Litten, Joseph

    2017-03-01

    Sigma metrics can be used to predict assay quality, allowing easy comparison of instrument quality and predicting which tests will require minimal quality control (QC) rules to monitor the performance of the method. A Six Sigma QC program can result in fewer controls and fewer QC failures for methods with a sigma metric of 5 or better. The higher the number of methods with a sigma metric of 5 or better, the lower the costs for reagents, supplies, and control material required to monitor the performance of the methods.

  2. 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.

  3. Bleach boosting effect of xylanase A from Bacillus halodurans C-125 in ECF bleaching of wheat straw pulp.

    PubMed

    Lin, Xiao-qiong; Han, Shuang-yan; Zhang, Na; Hu, Hui; Zheng, Sui-ping; Ye, Yan-rui; Lin, Ying

    2013-02-05

    Past studies have revealed major difficulties in applications of xylanase in the pulp and paper industry as enzymes isolated from many different species could not tolerate high temperatures or highly alkaline conditions. The thermostable xylanase A from Bacillus halodurans C-125 (C-125 xylanase A) was successfully cloned and expressed in Pichia pastoris with a yield as high as 3361 U/mL in a 2 L reactor. Its thermophilic and basophilic properties (optimal activity at 70 °C and pH 9.0), together with the fact it is cellulase-free, render this enzyme attractive for compatible applications in the pulp and paper industry. The pretreatment of wheat straw pulp with C-125 xylanase A at pH 9.0 and 70 °C for 90 min induced the release of both chromophores (Ab(237), Ab(254), Ab(280)) and hydrophobic compounds (Ab(465)) into the filtrate as well as sugar degradation. Moreover, the addition of 10 U xylanase to 1 g wheat straw pulp (dry weight) as pretreatment improved brightness by 5.2% ISO and decreased the kappa number by 5.0% when followed by hydrogen peroxide bleaching. In addition, compared with two commercial enzymes, Pulpzyme HC and AU-PE89, which are normally incorporated in ECF bleaching of wheat straw pulp, C-125 xylanase A proved to be more effective in enhancing brightness as well as preserving paper strength properties. When evaluating the physical properties of pulp samples, such as tensile index, tearing index, bursting index, and post-color (PC) number, the enzymes involved in pretreating pulps exhibited better or the same performances as chemical treatment. Compared with chemical bleaching, chlorine consumption can be significantly reduced by 10% for xylanase-pretreated wheat straw pulp while maintaining the brightness together with the kappa number at the same level. Scanning electron microscopy revealed significant surface modification of enzyme-pretreated pulp fibers with no marked fiber disruptions.

  4. 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 $\\Sigma^0(1385) \\to \\Lambda\\gamma$.

  5. 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.

  6. TA-55 and Sigma Overview

    SciTech Connect

    Spearing, Dane Robert

    2016-11-29

    These are slides from a facility overview presentation for visiting agencies to Los Alamos National Laboratory (LANL). The TA-55 Plutonium Facility (PF-4) is discussed in detail. PF-4 is a unique resource for US plutonium programs. The basic design is flexible and has adapted to changing national needs. It is a robust facility with strong safety and security implementation. It supports a variety of national programs. It will continue for many years into the future. Sigma is then discussed in detail, which handles everything from hydrogen to uranium. It has been in long term service to the Nation (nearly 60 years). It has a flexible authorization basis to handle almost the entire periodic table. It has a wide breadth of prototyping and characterization capabilities. It has integrated program and line management.

  7. [Involvement of sigma S and sigma 70 subunits of RNA polymerase and the CRP protein in the regulation of microcin C51 operon expression].

    PubMed

    Veselovskiĭ, A M; Bass, I A; Zolotukhina, M A; Mironov, A S; Metlitskaia, A Z; Khmel', I A

    2004-11-01

    Expression of the microcin C51 operon in Escherichia coli cells is activated during cell entry into the stationary growth phase and depends on the sigmaS subunit of RNA polymerase (RpoS). The null rpoS mutations retained the residual expression level of the transcriptional P(mcc)-lac fusion, which indicates that other sigma subunit can participate in the regulation of transcription of the microcin C51 operon. Data presented in this work show that the overproduction of sigma70 in rpoS- cells diminished the level of P(mcc)-lac expression, as in wild-type cells, which seems to be the consequence of competition between sigma factors for a limited number of core RNA polymerase molecules. In the presence of the rpoD800 mutation that renders sigma70 temperature-sensitive, expression of P(mcc)-lac was not induced in the phase of delayed culture growth at nonpermissive temperature, which indicates that sigma70 is indispensable for microcin operon expression. Point substitutions in the -10 P(mcc) region, leading to the formation of 5'-TGaTATAAT-3' site, enhanced promoter activity but did not affect the relationship between P(mcc)-lac transcription and growth phase, sigmaS, and the activator protein CRP. The activator protein CRP was shown to bind a DNA fragment containing the TGTGA(AATGAA)TCTAT site in the -59.5 bp position relative to the start site of transcription. Mutation in the ssrI gene encoding 6S RNA did not disturb P9mcc)-lac expression; these results indicate that 6S RNA does not participate in the regulation of microcin C51 operon expression.

  8. 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.

  9. 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

  10. Correlation between neuroleptic binding to sigma(1) and sigma(2) receptors and acute dystonic reactions.

    PubMed

    Matsumoto, R R; Pouw, B

    2000-08-04

    Acute dystonic reactions are motor side effects that occur soon after the initiation of neuroleptic treatment. Although earlier studies indicate that these abnormal movements can be induced in animals and humans via activation of sigma receptors, the relative contribution of the different sigma receptor subtypes is unknown. Since sigma(1) and sigma(2) receptor are differentially represented in motor regions of the brain, the affinities of 17 neuroleptics for these sigma receptor subtypes were determined using competition binding studies. The results revealed that most neuroleptics do not exhibit selectivity for either of the sigma receptor subtypes, as reflected by a significant correlation between the affinities of the neuroleptics for sigma(1) vs. sigma(2) receptors. Moreover, when the sigma binding affinities of the neuroleptics were correlated with the tendency of the drugs to produce acute dystonic reactions in humans, there was a significant correlation for both subtypes. Together with earlier studies in animals, the data suggest that neuroleptic-induced motor side effects can be mediated through both sigma(1) and sigma(2) receptors.

  11. The Prc and RseP proteases control bacterial cell-surface signalling activity.

    PubMed

    Bastiaansen, Karlijn C; Ibañez, Aurelia; Ramos, Juan L; Bitter, Wilbert; Llamas, María A

    2014-08-01

    Extracytoplasmic function (ECF) sigma factors play a key role in the regulation of vital functions in the bacterial response to the environment. In Gram-negative bacteria, activity of these sigma factors is often controlled by cell-surface signalling (CSS), a regulatory system that also involves an outer membrane receptor and a transmembrane anti-sigma factor. To get more insight into the molecular mechanism behind CSS regulation, we have focused on the unique Iut system of Pseudomonas putida. This system contains a hybrid protein containing both a cytoplasmic ECF sigma domain and a periplasmic anti-sigma domain, apparently leading to a permanent interaction between the sigma and anti-sigma factor. We show that the Iut ECF sigma factor regulates the response to aerobactin under iron deficiency conditions and is activated by a proteolytic pathway that involves the sequential action of two proteases: Prc, which removes the periplasmic anti-sigma domain, and RseP, which subsequently removes the transmembrane domain and thereby generates the ECF active transcriptional form. We furthermore demonstrate the role of these proteases in the regulation of classical CSS systems in which the sigma and anti-sigma factors are two different proteins.

  12. 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.

  13. The biHermitian topological sigma model

    NASA Astrophysics Data System (ADS)

    Zucchini, Roberto

    2006-12-01

    BiHermitian geometry, discovered long ago by Gates, Hull and Rocek, is the most general sigma model target space geometry allowing for (2,2) world sheet supersymmetry. By using the twisting procedure proposed by Kapustin and Li, we work out the type A and B topological sigma models for a general biHermtian target space, we write down the explicit expression of the sigma model's action and BRST transformations and present a computation of the topological gauge fermion and the topological action.

  14. 78 FR 39339 - Importer of Controlled Substances; Notice of Registration; SA INTL GMBH C/O., Sigma Aldrich Co., LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-01

    ... Substances; Notice of Registration; SA INTL GMBH C/O., Sigma Aldrich Co., LLC By Notice dated March 20, 2013, and published in the Federal Register on March 28, 2013, 78 FR 19015, SA INTL GMBH C/O., Sigma Aldrich... the factors in 21 U.S.C. 823(a) and 952(a), and determined that the registration of SA INTL GMBH...

  15. Performance Test for the SIGMA Communication System

    NASA Astrophysics Data System (ADS)

    Jeong, Seonyeong; Lee, Hyojeong; Lee, Seongwhan; Shin, Jehyuck; Lee, Jungkyu; Jin, Ho

    2016-12-01

    Scientific CubeSat with Instruments for Global Magnetic Fields and Radiations (SIGMA) is a 3-U size CubeSat that will be operated in low earth orbit (LEO). The SIGMA communication system uses a very high frequency (VHF) band for uplink and an ultra high frequency (UHF) band for downlink. Both frequencies belong to an amateur band. The ground station that communicates with SIGMA is located at Kyung Hee Astronomical Observatory (KHAO). For reliable communication, we carried out a laboratory (LAB) test and far-field tests between the CubeSat and a ground station. In the field test, we considered test parameters such as attenuation, antenna deployment, CubeSat body attitude, and Doppler frequency shift in transmitting commands and receiving data. In this paper, we present a communication performance test of SIGMA, a link budget analysis, and a field test process. We also compare the link budget with the field test results of transmitting commands and receiving data.

  16. Supersymmetric {sigma}-models in 2-dimensions

    SciTech Connect

    Zumino, B. |

    1997-02-01

    The author gives a brief introduction to supersymmetric {sigma}-models in two space-time dimensions. The topics he covers are: the bosonic {sigma}-model; supersymmetry in two dimensions; complex manifolds; the Kaehler and hyper-Kaehler case; and chiral supersymmetries. The lesson to be learned from the lecture is that the number of supersymmetries is intimately related to the geometric structure of the target space manifold: more geometric structure corresponds to more supersymmetries.

  17. 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.

  18. Elevated levels of sigma S inhibit biofilm formation in Escherichia coli: a role for the Rcs phosphorelay.

    PubMed

    Ferrières, Lionel; Thompson, Aoife; Clarke, David J

    2009-11-01

    The Rcs phosphorelay is composed of RcsC, RcsD and the response regulator RcsB, and this signalling pathway has been implicated in virulence and biofilm formation in many enteric bacteria. It was previously shown that a mutation in rcsC resulted in defective biofilm formation in Escherichia coli [Ferrières, L. & Clarke, D. J. (2003) Mol Microbiol 50, 1665-1682]. To identify the molecular mechanisms underlying the observed biofilm defect we carried out a screen looking for suppressor mutants that restored biofilm formation in the rcsC mutant background. One of the mutants was identified to be in rprA, a gene encoding a small RNA molecule that is involved in the post-transcriptional control of the alternative sigma factor, sigma(S). The expression of rprA is regulated by the Rcs phosphorelay, and there are elevated sigma(S) levels present in the rcsC mutant due to the overexpression of rprA in this background. Using different approaches, we have established that the increase in sigma(S) levels is responsible for the biofilm defect. Therefore, the Rcs phosphorelay is involved in maintaining appropriate levels of sigma(S) during biofilm formation in E. coli.

  19. Degradation of sigma 32, the heat shock regulator in Escherichia coli, is governed by HflB.

    PubMed Central

    Herman, C; Thévenet, D; D'Ari, R; Bouloc, P

    1995-01-01

    The heat shock response in Escherichia coli is governed by the concentration of the highly unstable sigma factor sigma 32. The essential protein HflB (FtsH), known to control proteolysis of the phage lambda cII protein, also governs sigma 32 degradation: an HflB-depleted strain accumulated sigma 32 and induced the heat shock response, and the half-life of sigma 32 increased by a factor up to 12 in mutants with reduced HflB function and decreased by a factor of 1.8 in a strain overexpressing HflB. The hflB gene is in the ftsJ-hflB operon, one promoter of which is positively regulated by heat shock and sigma 32. The lambda cIII protein, which stabilizes sigma 32 and lambda cII, appears to inhibit the HflB-governed protease. The E. coli HflB protein controls the stability of two master regulators, lambda cII and sigma 32, responsible for the lysis-lysogeny decision of phage lambda and the heat shock response of the host. Images Fig. 2 Fig. 4 Fig. 5 PMID:7724592

  20. Sigma meson in vacuum and nuclear matter

    NASA Astrophysics Data System (ADS)

    Menchaca-Maciel, M. C.; Morones-Ibarra, J. R.

    2013-04-01

    We have obtained the value of the interaction constant g σππ that adjusts the values obtained in the E791 Collaboration at Fermilab and BES Collaboration at the Beijing Electron Positron Collider experiments. To get this we have used the concept of critical width to make compatible the parameters obtained from the Breit-Wigner formula and those obtained from the density function. Also, the total width and effective mass modification of the sigma meson in nuclear matter has been studied in the Walecka model, assuming that the sigma couples to a pair of nucleon-antinucleon states and to particle-hole states, including the in-medium effect of sigma-omega mixing. We have considered, for completeness, the coupling of sigma to two virtual pions. We have found that the sigma meson mass decreases with respect to its value in vacuum and that the contribution of the sigma-omega mixing effect on the mass shift is relevant.

  1. 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 +}

  2. The role of sigmaB in the stress response of Gram-positive bacteria -- targets for food preservation and safety.

    PubMed

    van Schaik, Willem; Abee, Tjakko

    2005-04-01

    The alternative sigma factor sigmaB modulates the stress response of several Gram-positive bacteria, including Bacillus subtilis and the food-borne human pathogens Bacillus cereus, Listeria monocytogenes and Staphylococcus aureus. In all these bacteria, sigmaB is responsible for the transcription of genes that can confer stress resistance to the vegetative cell. Recent findings indicate that sigmaB also plays an important role in antibiotic resistance, pathogenesis and cellular differentiation processes such as biofilm formation and sporulation. Although there are important differences in the regulation of sigmaB and in the set of genes regulated by sigmaB in B. subtilis, B. cereus, L. monocytogenes and S. aureus, there are also some conserved themes. A mechanistic understanding of the sigmaB activation processes and assessment of its regulon could provide tools for pathogen control and inactivation both in the food industry and clinical settings.

  3. An RpoS (sigmaS) homologue regulates acylhomoserine lactone-dependent autoinduction in Ralstonia solanacearum.

    PubMed

    Flavier, A B; Schell, M A; Denny, T P

    1998-05-01

    Many bacteria sense an appropriate growth condition or a critical population density for gene expression by producing acylhomoserine lactones (acyl-HSLs) that act as intercellular autoinduction signals. We recently showed that, in Ralstonia (Pseudomonas) solanacearum, a phytopathogenic bacterium, acyl-HSL production requires soll, which encodes a putative acyl-HSL synthase, and that its expression is positively regulated by the acyl-HSL-responsive SolR transcriptional regulator. This acyl-HSL-dependent autoinduction system is noteworthy because (i) it is regulated by a 'higher level' autoinducer system (responsive to 3-hydroxypalmitic acid methyl ester) via PhcA, a LysR-type transcriptional regulator and (ii) acyl-HSL production requires two additional unlinked loci. As reported here, cloning and sequencing of one of these other loci revealed that it encodes a homologue of RpoS, an alternative sigma factor (sigmaS) that in other bacteria activates gene expression during stationary phase or in response to stress conditions. R. solanacearum RpoS (RpoS(Rso)) was demonstrated to function as a sigma factor because when introduced in trans into an Escherichia coli rpoS mutant it largely restored expression of the RpoS-dependent bolAp1 gene. Mutation of rpoS(Rso) in R. solanacearum reduced survival during starvation and low pH conditions, but did not affect survival during exposure to hydrogen peroxide, high osmolarity or high temperature. This mutant was also altered in its production of several virulence factors and wilted tomato plants several days more slowly than the wild-type parent. Transcription of solR and soll were decreased in an rpoS(Rso) background (thereby reducing acyl-HSL production), but neither mutations in solR, soll or phcA nor addition of acyl-HSLs affected rpoS(Rso) expression. Therefore, in R. solanacearum the acyl-HSL-dependent autoinduction system is controlled both by a second autoinduction system and by the RpoS(Rso) sigma factor.

  4. 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).

  5. 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.

  6. Effect of metal ions on radical type and proton-coupled electron transfer channel: sigma-radical vs pi-radical and sigma-channel vs pi-channel in the imide units.

    PubMed

    Chen, Xiaohua; Xing, Dianxiang; Zhang, Liang; Cukier, Robert I; Bu, Yuxiang

    2009-12-01

    The mechanism of proton transfer (PT)/electron transfer (ET) in imide units, and its regulation by hydrated metal ions, was explored theoretically using density functional theory in a representative model (a nearly planar and cisoid complex between uracil and its N(3)-dehydrogenated radical, UU). In UU (sigma-radical), PT/ET normally occurs via a seven-center, cyclic proton-coupled sigma-electron sigma-channel transfer (PC(sigma)E(sigma)T) mechanism (3.8 kcal/mol barrier height) with a N(3)-->N(3') PT and an O(4)-->O(4') ET. Binding of hydrated metal ions to the dioxygen sites (O(2)/O(2') or/and O(4)/O(4')) of UU may significantly affect its PT/ET cooperative reactivity by changing the radical type (sigma-radical <--> pi-radical) and ET channel (sigma-channel <--> pi-channel), leading to different mechanisms, ranging from PC(sigma)E(sigma)T, to proton-coupled pi-electron sigma-channel transfer (PC(pi)E(sigma)T) to proton-coupled pi-electron pi-channel transfer (PC(pi)E(pi)T). This change originates from an alteration of the ordering of the UU moiety SOMO/HDMO (the singly occupied molecular orbital and the highest doubly occupied molecular orbital), induced by binding of the hydrated metal ions. It is a consequence of three associated factors: the asymmetric reactant structure, electron cloud redistribution, and fixing role of metal ions to structural backbone. The findings regarding the modulation of the PT/ET pathway via hydrated metal ions may provide valuable information for a greater understanding of PT/ET cooperative mechanisms, and an alternative way for designing imide-based molecular devices, such as molecular switches and molecular wires.

  7. 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.

  8. Tree level semileptonic {sigma}{sub b} to nucleon decay in light cone QCD sum rules

    SciTech Connect

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

    2009-08-01

    Using the most general form of the interpolating current of the heavy spin 1/2, {sigma}{sub b} baryon and distribution amplitudes of the nucleon, the transition form factors of the semileptonic {sigma}{sub b}{yields}Nl{nu} decay are calculated in the framework of light-cone QCD sum rules. It is obtained that the form factors satisfy the heavy quark effective theory relations. The obtained results for the related form factors are used to estimate the decay rate of this transition.

  9. 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.

  10. Interest and limits of the six sigma methodology in medical laboratory.

    PubMed

    Scherrer, Florian; Bouilloux, Jean-Pierre; Calendini, Ors'Anton; Chamard, Didier; Cornu, François

    2017-02-01

    The mandatory accreditation of clinical laboratories in France provides an incentive to develop real tools to measure performance management methods and to optimize the management of internal quality controls. Six sigma methodology is an approach commonly applied to software quality management and discussed in numerous publications. This paper discusses the primary factors that influence the sigma index (the choice of the total allowable error, the approach used to address bias) and compares the performance of different analyzers on the basis of the sigma index. Six sigma strategy can be applied to the policy management of internal quality control in a laboratory and demonstrates through a comparison of four analyzers that there is no single superior analyzer in clinical chemistry. Similar sigma results are obtained using approaches toward bias based on the EQAS or the IQC. The main difficulty in using the six sigma methodology lies in the absence of official guidelines for the definition of the total error acceptable. Despite this drawback, our comparison study suggests that difficulties with defined analytes do not vary with the analyzer used.

  11. Activity of mutant sigma F proteins truncated near the C terminus.

    PubMed Central

    Min, K T; Yudkin, M D

    1992-01-01

    sigma F, the product of the spoIIAC gene of Bacillus subtilis, is homologous in amino acid sequence throughout most of its length with several other sigma factors of B. subtilis and Escherichia coli. However, 8 residues from the C terminus the homology abruptly breaks down, suggesting that the C-terminal tail of the protein may be dispensable. It is known that an amber mutation at the 11th codon (wild-type glutamine 245) from the C terminus abolishes the function of the sigma factor. We have now placed chain-terminating codons at the ninth codon (wild-type lysine 247), the eighth codon (wild-type valine 248), or the seventh codon (wild-type glutamine 249) from the C terminus. We have tested the resulting mutants for their capacity to sporulate and for their ability to transcribe from a promoter (spoIIIG) that is normally read by RNA polymerase bound to sigma F (E sigma F). The results indicate that a mutant sigma F lacking the terminal 7 residues functions almost normally, which suggests that glutamine 249 is dispensable. By contrast, lysine 247 is crucial for the activity of sigma F: deletion of the 9 C-terminal residues totally inactivates the protein. When the terminal 8 residues were deleted, placing lysine 247 at the C terminus, the transcriptional activity of the factor is reduced by about 80%: we attribute this effect to neutralization of the positive charge of lysine 247 by formation of a salt bridge with the -COO- terminus. Images PMID:1429437

  12. Sigma Delta Dac Using Vhdl-Ams

    NASA Astrophysics Data System (ADS)

    Utage, S. A.; Dube, R. R.

    2010-11-01

    Sigma Delta Digital to analog converters (DACs) convert a binary number into a voltage directly proportional to the value of the binary number. A variety of applications use DACs including waveform generators and programmable voltage sources. This paper describes a Delta-Sigma DAC implemented in a FPGA. The only external circuitry required is a low pass filter comprised of just one resistor and one capacitor. Internal resource requirements are also minimal. The speed and flexible output structure of the FPGAs make them ideal for this application.

  13. 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.

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. [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.

  19. 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

  20. Sample dilution and bacterial community composition influence empirical leucine-to-carbon conversion factors in surface waters of the world's oceans.

    PubMed

    Teira, Eva; 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

    2015-12-01

    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.

  1. Virtual screening studies to identify novel inhibitors for Sigma F protein of Mycobacterium tuberculosis.

    PubMed

    Mustyala, Kiran Kumar; Malkhed, Vasavi; Chittireddy, Venkataramana Reddy; Vuruputuri, Uma

    2015-12-01

    Tuberculosis (TB) is one of the oldest threats to public health. TB is caused by the pathogen Mycobacterium tuberculosis (MTB). The Sigma factors are essential for the survival of MTB. The Sigma factor Sigma F (SigF) regulates genes expression under stress conditions. The SigF binds to RNA polymerase and forms a holoenzyme, which initiates the transcription of various genes. The Usfx, an anti-SigF protein, binds to SigF and alters the transcription initiation and gene expression. In the present work, virtual screening studies are taken up to identify the interactions between SigF and small molecular inhibitors which can inhibit the formation of holoenzyme. The studies reveal that ARG 104 and ARG 224 amino acid residues of SigF protein are forming important binding interactions with the ligands. The in silico ADME properties for the ligand data set are calculated to check the druggability of the molecules.

  2. Kac-Moody algebra and nonlinear sigma model

    NASA Astrophysics Data System (ADS)

    Ogura, Waichi; Hosoya, Akio

    1985-12-01

    We investigate the nonlinear sigma model over an arbitrary homogeneous space. Then it is shown that the sigma model realizes the Kac-Moody algebra as current algebra only if the homogeneous space is restricted to the group manifold.

  3. Sigma-1 receptor alters the kinetics of Kv1.3 voltage gated potassium channels but not the sensitivity to receptor ligands.

    PubMed

    Kinoshita, Maho; Matsuoka, Yoshikazu; Suzuki, Takeshi; Mirrielees, Jennifer; Yang, Jay

    2012-05-03

    Sigma1 receptors (Sigma1R) are intracellular chaperone proteins that bind psychotropic drugs and also clinically used drugs such as ketamine and haloperidol. Co-expression of the Sigma1R has been reported to enhance the sensitivity of several voltage-gated ion channels to Sigma1R ligands. Kv1.3 is the predominant voltage-gated potassium channel expressed in T lymphocytes with a documented role in immune activation. To gain a better understanding of Sigma1R modulation of Kv ion channels, we investigated the effects of Sigma1R co-expression on Kv1.3 physiology and pharmacology in ion channels expressed in Xenopus oocytes. We also explored the protein domains of Kv1.3 necessary for protein:protein interaction between Kv1.3 and Sigma1R through co-immunoprecipitation studies. Slowly inactivating outward-going currents consistent with Kv1.3 expression were elicited on step depolarizations. The current characterized by E(rev), V(1/2), and slope factor remained unchanged when co-expressed with Sigma1R. Analysis of inactivation time constant revealed a faster Kv1.3 current decay when co-expressed with Sigma1R. However the sensitivity to Sigma1R ligands remained unaltered when co-expressed with the Sigma1R in contrast to the previously reported modulation of ligand sensitivity in closely related Kv1.4 and Kv1.5 voltage gated potassium channels. Co-immunoprecipitation assays of various Kv1.3 truncation constructs indicated that the transmembrane domain of the Kv1.3 protein was responsible for the protein:protein interaction with the Sigma1R. Sigma1R likely interacts with different domains of Kv ion channel family proteins resulting in distinct modulation of different channels.

  4. The sigma receptor: evolution of the concept in neuropsychopharmacology.

    PubMed

    Hayashi, T; Su, Tp

    2005-10-01

    Although originally proposed as a subtype of opioid receptors, the sigma receptor is now confirmed to be a non-opioid receptor that binds diverse classes of psychotropic drugs. Sigma receptors are subdivided into two subtypes, sigma-1 and sigma-2. The sigma-1 receptor is a 25-kDa protein possessing one putative transmembrane domain and an endoplasmic reticulum retention signal. Sigma-1 receptors are highly expressed in deeper laminae of the cortex, olfactory bulb, nuclei of mesencephalon, hypothalamus, and Purkinje cells in the brain. Sigma-1 receptors are predominantly localized at the endoplasmic reticulum of both neurons and oligodendrocytes. From behavioral studies, sigma-1 receptors were shown to be involved in higher-ordered brain functions including memory and drug dependence. The actions mediated by sigma-1 receptors at the cellular level can be considered either as acute or chronic. The acute actions include the modulation of ion channels (i.e., K+ channel, NMDA receptors, IP3 receptors) and the sigma-1 receptor translocation. Chronic actions of sigma-1 receptors are basically considered to be the result of an up- or down regulation of the sigma-1 receptor itself. For example, the upregulation of sigma-1 receptors per se, even without exogenous ligands, promotes cellular differentiation and reconstitution of lipid microdomains (lipid rafts) in cultured cells. These findings together suggest that sigma-1 receptors might possess a constitutive biological activity, and that sigma-1 receptor ligands might merely work as modulators of the innate activity of this protein. Recent in vitro and in vitro studies strongly point to the possibility that sigma-1 receptors participate in membrane remodeling and cellular differentiation in the nervous system.

  5. 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.

  6. Hyperfine structures of the 2 (3)Sigma(g) (+), 3 (3)Sigma(g) (+), and 4 (3)Sigma(g) (+) states of Na(2).

    PubMed

    Liu, Yaoming; Li, Li; Lazarov, Guenadiy; Lazoudis, Angelos; Lyyra, A Marjatta; Field, Robert W

    2004-09-22

    The hyperfine structures of the 2 (3)Sigma(g) (+), 3 (3)Sigma(g) (+), and 4 (3)Sigma(g) (+) states of Na(2) have been resolved with sub-Doppler continuous wave perturbation facilitated optical-optical double resonance spectroscopy via A (1)Sigma(u) (+) approximately b (3)Pi(u) mixed intermediate levels. The hyperfine patterns of these three states are similar. The hyperfine splittings of the low rotational levels are all very close to the case b(betaS) limit. As the rotational quantum number increases, the hyperfine splittings become more complicated and the coupling cases become intermediate between cases b(betaS) and b(beta J) due to spin-rotation interaction. We present a detailed analysis of the hyperfine structures of these three (3)Sigma(g) (+) states, employing both case b(betaS) and b(beta J) coupling basis sets. The results show that the hyperfine splittings of the (3)Sigma(g) (+) states are mainly due to the Fermi-contact interaction. The Fermi contact constants for the two d sigma Rydberg states, the 2 (3)Sigma(g) (+) and 4 (3)Sigma(g) (+), are 245+/-5 MHz and 225+/-5 MHz, respectively, while the Fermi contact constant of the s sigma 3 (3)Sigma(g) (+) Rydberg state is 210+/-5 MHz. The diagonal spin-spin and spin-rotation constants, and nuclear spin-electronic spin dipolar interaction parameters of the 3 (3)Sigma(g) (+) and 4 (3)Sigma(g) (+) states are also obtained.

  7. 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.

  8. 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…

  9. 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.

  10. Narrow structure in {Lambda}d scattering near the {Sigma} threshold ({sub {Sigma}}{sup 3}He states)

    SciTech Connect

    Gibson, B.F.; Afnan, I.R.

    1991-12-31

    A separable-potential, Faddeev-type calculation of {Lambda}-deuteron scattering near the threshold for {Sigma} production is shown to produce structure (a resonance peak) in the cross section which lies below the {Sigma} threshold for two different YN ({Lambda}N-{Sigma}N coupled-channel) potential models. In one case the {Sigma}NN eigenvalue corresponds to a pole which lies below threshold (bound) and in the second case the poles lies above the threshold.

  11. 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.

  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. Sigma-Model Solitons on Noncommutative Spaces

    NASA Astrophysics Data System (ADS)

    Dabrowski, Ludwik; Landi, Giovanni; Luef, Franz

    2015-12-01

    We use results from time-frequency analysis and Gabor analysis to construct new classes of sigma-model solitons over the Moyal plane and over noncommutative tori, taken as source spaces, with a target space made of two points. A natural action functional leads to self-duality equations for projections in the source algebra. Solutions, having nontrivial topological content, are constructed via suitable Morita duality bimodules.

  14. Sigma-1 receptors are essential for capsaicin-induced mechanical hypersensitivity: studies with selective sigma-1 ligands and sigma-1 knockout mice.

    PubMed

    Entrena, José Manuel; Cobos, Enrique José; Nieto, Francisco Rafael; Cendán, Cruz Miguel; Gris, Georgia; Del Pozo, Esperanza; Zamanillo, Daniel; Baeyens, José Manuel

    2009-06-01

    We evaluated the role of sigma(1) receptors on capsaicin-induced mechanical hypersensitivity and on nociceptive pain induced by punctate mechanical stimuli, using wild-type and sigma(1) receptor knockout (sigma(1)-KO) mice and selective sigma(1) receptor-acting drugs. Mutation in sigma(1)-KO mice was confirmed by PCR analysis of genomic DNA and, at the protein level, by [(3)H](+)-pentazocine binding assays. Both wild-type and sigma(1)-KO mice not treated with capsaicin showed similar responses to different intensities of mechanical stimuli (0.05-8 g force), ranging from innocuous to noxious, applied to the hind paw. This indicates that sigma(1) gene inactivation does not modify the perception of punctate mechanical stimuli. The intraplantar (i.pl.) administration of capsaicin induced dose-dependent mechanical allodynia in wild-type mice (markedly reducing both the threshold force necessary to induce paw withdrawal and the latency to paw withdrawal induced by a given force). In contrast, capsaicin was completely unable to induce mechanical hypersensitivity in sigma(1)-KO mice. The high-affinity and selective sigma(1) antagonists BD-1063, BD-1047 and NE-100, administered subcutaneously (s.c.), dose-dependently inhibited mechanical allodynia induced by capsaicin (1 microg,i.pl.), yielding ED(50) (mg/kg) values of 15.80+/-0.93, 29.31+/-1.65 and 40.74+/-7.20, respectively. The effects of the sigma(1) antagonists were reversed by the sigma(1) agonist PRE-084 (32 mg/kg, s.c.). None of the drugs tested modified the responses induced by a painful mechanical punctate stimulus (4 g force) in nonsensitized animals. These results suggest that sigma(1) receptors are essential for capsaicin-induced mechanical hypersensitivity, but are not involved in mechanical nociceptive pain.

  15. Sigma receptors as potential therapeutic targets for neuroprotection.

    PubMed

    Nguyen, Linda; Kaushal, Nidhi; Robson, Matthew J; Matsumoto, Rae R

    2014-11-15

    Sigma receptors comprise a unique family of proteins that have been implicated in the pathophysiology and treatment of many central nervous system disorders, consistent with their high level of expression in the brain and spinal cord. Mounting evidence indicate that targeting sigma receptors may be particularly beneficial in a number of neurodegenerative conditions including Alzheimer׳s disease, Parkinson׳s disease, stroke, methamphetamine neurotoxicity, Huntington׳s disease, amyotrophic lateral sclerosis, and retinal degeneration. In this perspective, a brief overview is given on sigma receptors, followed by a focus on common mechanisms of neurodegeneration that appear amenable to modulation by sigma receptor ligands to convey neuroprotective effects and/or restorative functions. Within each of the major mechanisms discussed herein, the neuroprotective effects of sigma ligands are summarized, and when known, the specific sigma receptor subtype(s) involved are identified. Together, the literature suggests sigma receptors may provide a novel target for combatting neurodegenerative diseases through both neuronal and glial mechanisms.

  16. Mucosal vaccination by adenoviruses displaying reovirus sigma 1.

    PubMed

    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

    2015-08-01

    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.

  17. Characterization of the sigma 38-dependent expression of a core Escherichia coli starvation gene, pexB.

    PubMed

    Lomovskaya, O L; Kidwell, J P; Matin, A

    1994-07-01

    A reverse genetics approach was used to clone a pex starvation gene that codes for an 18-kDa polypeptide, designated PexB. Single-copy pexB-lacZ operon fusions were constructed to study transcriptional regulation and the promoter region of this gene. The induction by carbon starvation or osmotic stress was transcriptional and controlled by sigma 38 but was independent of this sigma factor by the oxidative stress; presumably, it was sigma 70 mediated under the latter stress. During nitrogen starvation, the induction was controlled at the posttranscriptional level. The pexB upstream region contained 245 nucleotides within which sequences approximating the consensus for cyclic AMP receptor protein and integration host factor binding sites were discernible. Deletion of 164 bp of the upstream region, which included these consensus sequences, did not affect starvation-or osmotic stress-mediated induction of pexB but abolished its induction by oxidative stress. The same start site was used in transcription during carbon starvation, osmotic stress, or oxidative stress, suggesting that the pexB promoter can be recognized in vivo by both sigma 38 and sigma 70, depending, presumably, on the presence of appropriate transcriptional factors. The -10 and -35 regions of pexB resembled those of some but not all genes known to be controlled by sigma 38.

  18. 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.

  19. 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).

  20. 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.

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

    DOE PAGES

    Jensen, Jaime L.; Balbo, Andrea; Neau, David B.; ...

    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

  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. A comparison of simulated precipitation by hybrid isentropic-sigma and sigma models

    NASA Technical Reports Server (NTRS)

    Johnson, Donald R.; Zapotocny, Tom H.; Reames, Fred M.; Wolf, Bart J.; Pierce, R. B.

    1993-01-01

    Simulations of dry and moist baroclinic development from 10- and 22-layer hybrid isentropic-sigma coordinate models are compared with those from 11-, 27-, and 35-layer sigma coordinate models. The ability of the models to transport water vapor and simulate equivalent potential temperature is examined. Predictions of the timing, location, and amount of precipitation are compared. Several analytical distributions of water vapor are specified initially. It is shown that when the relative humidity is vertically uniform through a substantial extent of the atmosphere, all the models produce very similar precipitation distributions. However, when water vapor is confined to relatively shallow layers, the ability of the sigma coordinate models to simulate the timing, location, and amount of precipitation is severely compromised.

  4. 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.

  5. 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.

  6. Lean Six Sigma Challenges and Opportunities

    DTIC Science & Technology

    2008-02-13

    St ra te gy R es ea rc h Pr oj ec t LEAN SIX SIGMA CHALLENGES AND OPPORTUNITIES BY COLONEL LINDA R. HERBERT United States Army ...not reflect the official policy or position of the Department of the Army , Department of Defense, or the U.S. Government. U.S. Army War College...5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) U.S. Army War College ,122 Forbes Ave

  7. Euclidean supersymmetry, twisting and topological sigma models

    NASA Astrophysics Data System (ADS)

    Hull, C. M.; Lindström, U.; Melo dos Santos, L.; von Unge, R.; Zabzine, M.

    2008-06-01

    We discuss two dimensional N-extended supersymmetry in Euclidean signature and its R-symmetry. For N = 2, the R-symmetry is SO(2) × SO(1, 1), so that only an A-twist is possible. To formulate a B-twist, or to construct Euclidean N = 2 models with H-flux so that the target geometry is generalised Kahler, it is necessary to work with a complexification of the sigma models. These issues are related to the obstructions to the existence of non-trivial twisted chiral superfields in Euclidean superspace.

  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. 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.

  11. Characterization of the Alternative Sigma Factor σ54 and the Transcriptional Regulator FleQ of Legionella pneumophila, Which Are Both Involved in the Regulation Cascade of Flagellar Gene Expression

    PubMed Central

    Jacobi, Sebastian; Schade, Rüdiger; Heuner, Klaus

    2004-01-01

    We cloned and analyzed Legionella pneumophila Corby homologs of rpoN (encoding σ54) and fleQ (encoding σ54 activator protein). Two other genes (fleR and pilR) whose products have a σ54 interaction domain were identified in the genome sequence of L. pneumophila. An rpoN mutant strain was nonflagellated and expressed very small amounts of the FlaA (flagellin) protein. Like the rpoN mutant, the fleQ mutant strain of L. pneumophila was also nonflagellated and expressed only small amounts of FlaA protein compared to the amounts expressed by the wild type. In this paper we show that the σ54 factor and the FleQ protein are involved in regulation of flagellar gene operons in L. pneumophila. RpoN and FleQ positively regulate the transcription of FliM and FleN, both of which have a σ54-dependent promoter consensus sequence. However, they seemed to be dispensable for transcription of flaA, fliA, or icmR. Our results confirmed a recently described model of the flagellar gene regulation cascade in L. pneumophila (K. Heuner and M. Steinert, Int. J. Med. Microbiol. 293:133-145, 2003). Flagellar gene regulation was found to be different from that of Enterobacteriaceae but seems to be comparable to that described for Pseudomonas or Vibrio spp. PMID:15090493

  12. Sigma-1 receptors modulate functional activity of rat splenocytes.

    PubMed

    Liu, Y; Whitlock, B B; Pultz, J A; Wolfe, S A

    1995-06-01

    Neuroleptics, opiates, and cocaine are commonly prescribed for or abused by humans. Although primarily used for their actions at other receptors in brain, these compounds also act at sigma receptors. We have previously identified sigma-1 receptors on human peripheral blood leukocytes and rat spleen, and in the present study we demonstrate a correlation between the pharmacology of these receptors and the ability of drugs to suppress concanavalin A-induced splenocyte proliferation. These results support the hypothesis that sigma-1 receptors regulate functional activities of immune cells, and suggest that sigma agonists may cause changes in immune competence in vivo.

  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. Role and regulation of sigma S in general resistance conferred by low-shear simulated microgravity in Escherichia coli.

    PubMed

    Lynch, S V; Brodie, E L; Matin, A

    2004-12-01

    Life on Earth evolved in the presence of gravity, and thus it is of interest from the perspective of space exploration to determine if diminished gravity affects biological processes. Cultivation of Escherichia coli under low-shear simulated microgravity (SMG) conditions resulted in enhanced stress resistance in both exponential- and stationary-phase cells, making the latter superresistant. Given that microgravity of space and SMG also compromise human immune response, this phenomenon constitutes a potential threat to astronauts. As low-shear environments are encountered by pathogens on Earth as well, SMG-conferred resistance is also relevant to controlling infectious disease on this planet. The SMG effect resembles the general stress response on Earth, which makes bacteria resistant to multiple stresses; this response is sigma s dependent, irrespective of the growth phase. However, SMG-induced increased resistance was dependent on sigma s only in stationary phase, being independent of this sigma factor in exponential phase. sigma s concentration was some 30% lower in exponential-phase SMG cells than in normal gravity cells but was twofold higher in stationary-phase SMG cells. While SMG affected sigma s synthesis at all levels of control, the main reasons for the differential effect of this gravity condition on sigma s levels were that it rendered the sigma protein less stable in exponential phase and increased rpoS mRNA translational efficiency. Since sigma s regulatory processes are influenced by mRNA and protein-folding patterns, the data suggest that SMG may affect these configurations.

  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. 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.

  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. Targeting the sigma-1 receptor chaperone in the treatment of perinatal brain injury.

    PubMed

    Hashimoto, Kenji

    2015-03-01

    Glutamate-induced excitotoxicity via the N-methyl-d-aspartate (NMDA) receptor is an important factor in the pathogenesis of perinatal brain injury. The sigma-1 receptor on the endoplasmic reticulum (ER) has been known to affect the function of the NMDA receptor. 4-Phenyl-1-(4-phenylbutyl)piperidine (PPBP) has been investigated as a sigma-1 receptor agonist for several decades. An article using PPBP in a model of preterm brain injury was published in Experimental Neurology. The authors reported that PPBP protected against glutamate-induced excitotoxicity in primary hippocampal neurons. Furthermore, the systemic administration of PPBP significantly reduced microglial activation and lesion size in cortical gray and white matter after the excitotoxic insult in neonatal mice. This study suggests that sigma-1 receptor agonists could be potential preventive and therapeutic drugs for perinatal brain injury, although a pharmacological experiment using a sigma-1 receptor antagonist was not performed. This commentary aims to highlights the key findings of this article in a broader context, emphasizing the future potential therapeutic applications in patients with perinatal brain injury.

  19. Early development of sigma-receptor ligands.

    PubMed

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

    2011-01-01

    Sigma receptors (σ-1 and σ-2) are non-opioid proteins implicated in the pathophysiology of various neurological disorders and cancer. The σ-1 subtype is a chaperon protein widely distributed in the CNS and peripheral tissues. These receptors are involved in the modulation of K(+)- and Ca(2+)-dependent signaling cascades at the endoplasmic reticulum and modulation of neurotransmitter release. σ-1 receptors are emerging targets for the treatment of neurophychiatric diseases (schizophrenia and depression) and cocaine addiction. σ-2 receptors are lipid raft proteins. They are highly expressed on many tumor cells and hence considered potential targets for anticancer drugs. σ receptors bind to a diverse class of pharmacological compounds like cocaine, methamphetamine, benzomorphans like (±)-pentazocine, (±)-SKF-10,047 and endogenous neurosteroids and sphingolipids. In this review we focus on the early development of σ receptor-specific ligands and radiolabeling agents.

  20. Conversations with Early Leaders of Eta Sigma Gamma

    ERIC Educational Resources Information Center

    Clark, Jeffrey K.; Seabert, Denise M.; Goldsmith, Mal

    2007-01-01

    Anniversaries are often a time to reflect on the past. With that in mind, interviews were conducted with early key leaders of Eta Sigma Gamma to explore their perspectives of the organization's growth and development as well as their hopes for the future of ESG. The individuals interviewed included the surviving founders of Eta Sigma Gamma, the…

  1. Sigma-1 receptor: the novel intracellular target of neuropsychotherapeutic drugs.

    PubMed

    Hayashi, Teruo

    2015-01-01

    Sigma-1 receptor ligands have been long expected to serve as drugs for treatment of human diseases such as neurodegenerative disorders, depression, idiopathic pain, drug abuse, and cancer. Recent research exploring the molecular function of the sigma-1 receptor started unveiling underlying mechanisms of the therapeutic activity of those ligands. Via the molecular chaperone activity, the sigma-1 receptor regulates protein folding/degradation, ER/oxidative stress, and cell survival. The chaperone activity is activated or inhibited by synthetic sigma-1 receptor ligands in an agonist-antagonist manner. Sigma-1 receptors are localized at the endoplasmic reticulum (ER) membranes that are physically associated with the mitochondria (MAM: mitochondria-associated ER membrane). In specific types of neurons (e.g., those at the spinal cord), sigma-1 receptors are also clustered at ER membranes that juxtapose postsynaptic plasma membranes. Recent studies indicate that sigma-1 receptors, partly in sake of its unique subcellular localization, regulate the mitochondria function that involves bioenergetics and free radical generation. The sigma-1 receptor may thus provide an intracellular drug target that enables controlling ER stress and free radical generation under pathological conditions.

  2. Trifluoromethylsulfonyl derivatives of benzofuroxane and their anionic sigma-complexes

    SciTech Connect

    Yagupol'skii, L.M.; Gogoman, I.V.; Shchupak, G.M.; Boiko, V.N.

    1986-09-10

    Syntheses are reported for 4-nitro-6-trifluoromethylsulfonyl- and 4,6-bis(trifluoromethylsulfonyl)benzofuroxanes and their anionic sigma-complexes with hydroxide and methylate anions. In contrast to its 4,6-dinitro analog, 4,6-bis(trifluoromethylsulfonyl)benzofuroxane forms stable sigma-complexes with sodium acetate and sodium azide and has higher acidity by an order of magnitude.

  3. 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.

  4. SIGMA Final Report: Volume V, Part 4. The Design of SIGMA.

    DTIC Science & Technology

    1982-05-01

    sender , subject, date/time stamp, etc.--so that the message behind it is identifiable. It also specifies the nature of transmission, whether a message is...number, the new mail and alert counts, the load aerage, and the time of day. is generated and sent to the Driver. - Ithe user queue is not empty. the...deletes folders from the SIGMA folder database (DELETE-FOLDER). " It updates folders with delta file information (DELTA-UPDATE). * It creates inboxes

  5. 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

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

    PubMed

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

    2016-03-01

    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.

  7. Could sigma receptor ligands be a treatment for methamphetamine addiction?

    PubMed

    Rodvelt, Kelli R; Miller, Dennis K

    2010-09-01

    Methamphetamine's effects are generally considered to be mediated via monoamine transporters; however, it has comparable affinity for sigma receptors. Sigma receptors influence the downstream dopamine systems that are targeted by methamphetamine treatment. Research investigating the effect of sigma receptor agonists on methamphetamine-associated neurochemical and behavioral properties remains controversial; however, the general trend indicates an enhancement of stimulant effects. In contrast, sigma receptor antagonists attenuate methamphetamine-induced neurotoxic and behavioral properties. Together, these studies highlight an important role for sigma receptors in methamphetamine's addictive properties and the consequences of methamphetamine intoxication. Additional research is necessary to elucidate the precise mechanisms underlying their involvement and their role as a potential target for anti-methamphetamine pharmacotherapies.

  8. 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.

  9. The atypical two-subunit σ factor from Bacillus subtilis is regulated by an integral membrane protein and acid stress.

    PubMed

    Davis, Maria C; Smith, Logan K; MacLellan, Shawn R

    2016-02-01

    Extracytoplasmic function (ECF) σ factors constitute a major component of the physicochemical sensory apparatus in bacteria. Most ECF σ factors are co-expressed with a negative regulator called an anti-σ factor that binds to its cognate σ factor and sequesters it from productive association with core RNA polymerase (RNAP). Anti-σ factors constitute an important element of signal transduction pathways that mediate an appropriate transcriptional response to changing environmental conditions. The Bacillus subtilis genome encodes seven canonical ECF σ factors and six of these are co-expressed with experimentally verified anti-σ factors. B. subtilis also expresses an ECF-like atypical two-subunit σ factor composed of subunits SigO and RsoA that becomes active after exposure to certain cell-wall-acting antibiotics and to growth under acidic conditions. This work describes the identification and preliminary characterization of a protein (RsiO, formerly YvrL) that constitutes the anti-σ factor cognate to SigO-RsoA. Synthesis of RsiO represses SigO-RsoA-dependent transcription initiation by binding the N-terminus of SigO under neutral (pH 7) conditions. Reconstitution of the SigO-RsoA-RsiO regulatory system into a heterologous host reveals that the imposition of acid stress (pH 5.4) abolishes the ability of RsiO to repress SigO-RsoA-dependent transcription and this correlates with loss of RsiO binding affinity for SigO. A current model for RsiO function indicates that RsiO responds, either directly or indirectly, to increased extracytoplasmic hydrogen ion concentration and becomes inactivated. This results in the release of SigO into the cytoplasm, where it productively associates with RsoA and core RNAP to initiate transcription from target promoters in the cell.

  10. Sigma Receptors Suppress Multiple Aspects of Microglial Activation

    PubMed Central

    Hall Aaron, A.; Yelenis, Herrera; Ajmo Craig, T.; Javier, Cuevas; Pennypacker Keith, R.

    2009-01-01

    During brain injury, microglia become activated and migrate to areas of degenerating neurons. These microglia release pro-inflammatory cytokines and reactive oxygen species causing additional neuronal death. Microglia express high levels of sigma receptors, however, the function of these receptors in microglia and how they may affect the activation of these cells remain poorly understood. Using primary rat microglial cultures, it was found that sigma receptor activation suppresses the ability of microglia to rearrange their actin cytoskeleton, migrate, and release cytokines in response to the activators adenosine triphosphate (ATP), monocyte chemoattractant protein 1 (MCP-1), and lipopolysaccharide (LPS). Next, the role of sigma receptors in the regulation of calcium signaling during microglial activation was explored. Calcium fluorometry experiments in vitro show that stimulation of sigma receptors suppressed both transient and sustained intracellular calcium elevations associated with the microglial response to these activators. Further experiments showed that sigma receptors suppress microglial activation by interfering with increases in intracellular calcium. In addition, sigma receptor activation also prevented membrane ruffling in a calcium-independent manner, indicating that sigma receptors regulate the function of microglia via multiple mechanisms. PMID:19031439

  11. 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.

  12. Proteome investigation of the global regulatory role of sigma 54 in response to gentisate induction in Pseudomonas alcaligenes NCIMB 9867.

    PubMed

    Zhao, Bing; Yeo, Chew Chieng; Poh, Chit Laa

    2005-05-01

    Pseudomonas alcaligenes NCIMB 9867 (strain P25X) utilizes the gentisate pathway for the degradation of aromatic hydrocarbons. The gene encoding the alternative sigma (sigma) factor sigma(54), rpoN, was cloned from strain P25X and a rpoN knock-out strain, designated G54, was constructed by insertional inactivation with a kanamycin resistance gene cassette. The role of sigma(54) in the physiological response of P. alcaligenes P25X to gentisate induction was assessed by comparing the global protein expression profiles of the wild-type P25X with the rpoN mutant strain G54. Analysis of two-dimensional polyacrylamide gel electrophoresis gels showed that 39 out of 355 prominent protein spots exhibited differential expression as a result of the insertional inactivation of rpoN. Identification of the protein spots by matrix-assisted laser desorption/ionization-time of flight/time of flight revealed a wide diversity of proteins that are affected by the sigma(54) mutation, the largest group being proteins that are involved in carbon metabolism. The strictly inducible gentisate 1,2-dioxygenase, one of two isofunctional copies of the key enzyme in the gentisate pathway, and enzymes of the TCA cycle, pyruvate metabolism and gluconeogenesis were part of this group. Other proteins that are part of the sigma(54) regulon include enzymes implicated in nitrogen metabolism, transport proteins, stress-response proteins and proteins involved in cell motility. The results of this study showed that sigma(54) plays a global regulatory role in the expression of a wide variety of genes in P. alcaligenes, including the wild-type response to the presence of the aromatic inducer, gentisate.

  13. Sigma: Web Retrieval Interface for Nuclear Reaction Data

    SciTech Connect

    Pritychenko, B. Sonzogni, A.A.

    2008-12-15

    We 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 (http://www.nndc.bnl.gov/sigma)

  14. Comments on HKT supersymmetric sigma models and their Hamiltonian reduction

    NASA Astrophysics Data System (ADS)

    Fedoruk, Sergey; Smilga, Andrei

    2015-05-01

    Using complex notation, we present new simple expressions for two pairs of complex supercharges in HKT (‘hyper-Kähler with torsion’) supersymmetric sigma models. The second pair of supercharges depends on the holomorphic antisymmetric ‘hypercomplex structure’ tensor {{I}jk} which plays the same role for the HKT models as the complex structure tensor for the Kähler models. When the Hamiltonian and supercharges commute with the momenta conjugate to the imaginary parts of the complex coordinates, one can perform a Hamiltonian reduction. The models thus obtained represent a special class of quasicomplex sigma models introduced recently by Ivanov and Smilga (2013 SIGMA 9 069)

  15. 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.

  16. On the sigma-model of deformed special geometry

    NASA Astrophysics Data System (ADS)

    Lopes Cardoso, Gabriel; Véliz-Osorio, Alvaro

    2013-07-01

    We discuss the deformed sigma-model that arises when considering four-dimensional N=2 abelian vector multiplets in the presence of an arbitrary chiral background field. In addition, we allow for a class of deformations of special geometry by non-holomorphic terms. We analyze the geometry of the sigma-model in terms of intrinsic torsion classes. We show that, generically, the deformed geometry is non-Kähler. We illustrate our findings with an example. We also express the deformed sigma-model in terms of the Hesse potential that underlies the real formulation of special geometry.

  17. Sigma1 recognition sites in rabbit iris-ciliary body: topical sigma1-site agonists lower intraocular pressure.

    PubMed

    Bucolo, C; Campana, G; Di Toro, R; Cacciaguerra, S; Spampinato, S

    1999-06-01

    In this study, we examined the presence of sigma1 and sigma2 sites in the rabbit iris-ciliary body by receptor binding and investigated their effects on intraocular pressure (IOP) in albino rabbits. The iris-ciliary body has binding sites for the sigma1-site agonist [3H](+)-pentazocine (Kd = 4.6 nM; Bmax = 212 fmol/mg protein) and sigma2 sites labeled with [3H]1,3-di-o-tolylguanidine (DTG) (Kd = 8. 2 nM; Bmax = 1120 fmol/mg protein). In competition binding studies, (+)-pentazocine and the sigma antagonist NE-100 displayed high affinity for sigma1 sites (Ki = 2.1 and 2.4 nM, respectively), whereas (+)-N-allylnormetazocine (NANM) was less potent (Ki = 178 nM). Unilateral topical (+)-pentazocine (0.01-0.1%) caused a significant dose-related reduction of IOP in ocular normotensive rabbits and in the alpha-chymotrypsin model of ocular hypertension. (+)-NANM was less potent than (+)-pentazocine. Neither compound altered the IOP of the contralateral eye, and their hypotensive activity was blocked by NE-100 that, by itself, had no effect on IOP. (-)-Pentazocine, (-)-NANM, and DTG had no effect on IOP. DTG prevented the hypotensive effect of (+)-pentazocine, suggesting that it acts as a sigma1-site antagonist. sigma-Site ligands did not affect pupil diameter or cause ocular inflammation. Topical [3H](+)-pentazocine reaches the intraocular tissues within 30 min, and its uptake in the iris-ciliary body and retina was significantly reduced by topical pretreatment with NE-100, as expected for a receptor-specific agent. Reverse-phase HPLC confirmed the presence of intact (+)-pentazocine in iris-ciliary body homogenates. sigma1-Site agonists may offer a novel class of agents potentially effective in the control of ocular hypertension.

  18. M sub 1 muscarinic antagonists interact with. sigma. recognition sites

    SciTech Connect

    Hudkins, R.L. ); DeHaven-Hudkins, D.L. )

    1991-01-01

    The M{sub 1}-selective muscarinic antagonists aprophen, caramiphen, carbetapentane, 2-DAEX, dicyclomine, hexahydrosiladifenidol, iodocaramiphen, nitrocaramiphen, oxybutynin and trihexyphenidyl potently inhibited binding to {sigma} sites in brain. Both basic ester and non-ester structural type compounds which exhibit affinity for the muscarinic receptor also demonstrated affinity for the {sigma} site, while the classical antimuscarinic agents atropine and QNB, and the tricyclic pirenzepine, were ineffective in binding to this site. The authors also observed a significant correlation between the K{sub i} values for {sigma}compounds to inhibit ({sup 3}H)pirenzepine binding and their IC{sub 50} values to inhibit carbachol-stimulated phosphoinositide turnover. These observations may aid in elucidating the relationship of {sigma} binding to inhibition of phosphoinositide turnover stimulated by cholinergic agonists.

  19. 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.

  20. Blue shifts vs red shifts in sigma-hole bonding.

    PubMed

    Murray, Jane S; Concha, Monica C; Lane, Pat; Hobza, Pavel; Politzer, Peter

    2008-08-01

    Sigma-hole bonding is a noncovalent interaction between a region of positive electrostatic potential on the outer surface of a Group V, VI, or VII covalently-bonded atom (a sigma-hole) and a region of negative potential on another molecule, e.g., a lone pair of a Lewis base. We have investigated computationally the occurrence of increased vibration frequencies (blue shifts) and bond shortening vs decreased frequencies (red shifts) and bond lengthening for the covalent bonds to the atoms having the sigma-holes (the sigma-hole donors). Both are possible, depending upon the properties of the donor and the acceptor. Our results are consistent with models that were developed earlier by Hermansson and by Qian and Krimm in relation to blue vs red shifting in hydrogen bond formation. These models invoke the derivatives of the permanent and the induced dipole moments of the donor molecule.

  1. 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.

  2. 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.

  3. Hamilton-Jacobi approach to cosmology with nonlinear sigma model

    NASA Astrophysics Data System (ADS)

    Kerner, Richard; van Holten, Jan-Willem

    2016-05-01

    We start with a short introduction of the role that constraints and Lagrange multiplers play in variational calculus. After recalling briefly the properties of the nonlinear sigma model, we show how the Hamilton-Jacobi method can be applied to find its solutions. We discuss the importance of the Hamiltonian constraint in the standard cosmological model, and finally, apply the Hamilton-Jacobi method to the solution of coupled gravitational and sigma-field equations.

  4. Killing Sections and Sigma Models with Lie Algebroid Targets

    NASA Astrophysics Data System (ADS)

    Bruce, Andrew James

    2016-08-01

    We define and examine the notion of a Killing section of a Riemannian Lie algebroid as a natural generalisation of a Killing vector field. We show that the various expression for a vector field to be Killing naturally generalise to the setting of Lie algebroids. As an application we examine the internal symmetries of a class of sigma models for which the target space is a Riemannian Lie algebroid. Critical points of these sigma models are interpreted as generalised harmonic maps.

  5. 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.

  6. Transcription factor-based biosensor

    DOEpatents

    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.

  7. The cholinergic system, sigma-1 receptors and cognition.

    PubMed

    van Waarde, Aren; Ramakrishnan, Nisha K; Rybczynska, Anna A; Elsinga, Philip H; Ishiwata, Kiichi; Nijholt, Ingrid M; Luiten, Paul G M; Dierckx, Rudi A

    2011-08-10

    This article provides an overview of present knowledge regarding the relationship between the cholinergic system and sigma-1 receptors, and discusses potential applications of sigma-1 receptor agonists in the treatment of memory deficits and cognitive disorders. Sigma-1 receptors, initially considered as a subtype of the opioid family, are unique ligand-regulated molecular chaperones in the endoplasmatic reticulum playing a modulatory role in intracellular calcium signaling and in the activity of several neurotransmitter systems, particularly the cholinergic and glutamatergic pathways. Several central nervous system (CNS) drugs show high to moderate affinities for sigma-1 receptors, including acetylcholinesterase inhibitors (donepezil), antipsychotics (haloperidol, rimcazole), selective serotonin reuptake inhibitors (fluvoxamine, sertraline) and monoamine oxidase inhibitors (clorgyline). These compounds can influence cognitive functions both via their primary targets and by activating sigma-1 receptors in the CNS. Sigma-1 agonists show powerful anti-amnesic and neuroprotective effects in a large variety of animal models of cognitive dysfunction involving, among others (i) pharmacologic target blockade (with muscarinic or NMDA receptor antagonists or p-chloroamphetamine); (ii) selective lesioning of cholinergic neurons; (iii) CNS administration of β-amyloid peptides; (iv) aging-induced memory loss, both in normal and senescent-accelerated rodents; (v) neurodegeneration induced by toxic compounds (CO, trimethyltin, cocaine), and (vi) prenatal restraint stress.

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

    PubMed

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

    2007-11-21

    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.

  9. sigma-1 receptors in major depression and anxiety.

    PubMed

    Kulkarni, Shrinivas K; Dhir, Ashish

    2009-07-01

    Major depression and anxiety are two of the major psychiatric disorders that have some overlapping pathophysiologies, the most significant being the dysfunction in the monoaminergic, GABAergic and glutamatergic systems. A large number of drugs that alter these neurotransmitter levels/systems are effective in the treatment of major depression and anxiety. However, full remission of the clinical symptoms has not been achieved, perhaps owing to the complex pathophysiology of the diseases. Thus, the search for newer targets and target-specific drugs continues. Recently, the role of sigma-receptors, particularly the sigma-1 receptor subtype, has been identified as a target for the pathophysiology of neuropsychiatric disorders, and sigma-1 receptor modulators are considered to be the drugs of the future for the treatment of major depression and anxiety. The present review attempts to discuss the role of sigma-1 receptors in the pathophysiology of major depression and anxiety and also tries to position the use of its receptor modulators in the treatment of these two major disorders. The role of sigma-1 receptors in the mechanism of antidepressant action of venlafaxine, bupropion, neurosteroids and one of the herbal antidepressants, berberine, is reviewed. Although, sigma-1 receptor modulators may be future therapeutic options, either as individual agents or adjuvants in the treatment of mental disorders, the topic needs further preclinical and clinical exploration.

  10. 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.

  11. 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...

  12. 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.

  13. SN79, a sigma receptor ligand, blocks methamphetamine-induced microglial activation and cytokine upregulation.

    PubMed

    Robson, Matthew J; Turner, Ryan C; Naser, Zachary J; McCurdy, Christopher R; Huber, Jason D; Matsumoto, Rae R

    2013-09-01

    Methamphetamine (METH) abuse is associated with several negative side effects including neurotoxicity in specific brain regions such as the striatum. The precise molecular mechanisms by which METH usage results in neurotoxicity remain to be fully elucidated, with recent evidence implicating the importance of microglial activation and neuroinflammation in damaged brain regions. METH interacts with sigma receptors which are found in glial cells in addition to neurons. Moreover, sigma receptor antagonists have been shown to block METH-induced neurotoxicity in rodents although the cellular mechanisms underlying their neuroprotection remain unknown. The purpose of the current study was to determine if the prototypic sigma receptor antagonist, SN79, mitigates METH-induced microglial activation and associated increases in cytokine expression in a rodent model of METH-induced neurotoxicity. METH increased striatal mRNA and protein levels of cluster of differentiation 68 (CD68), indicative of microglial activation. METH also increased ionized calcium binding adapter molecule 1 (IBA-1) protein expression, further confirming the activation of microglia. Along with microglial activation, METH increased striatal mRNA expression levels of IL-6 family pro-inflammatory cytokines, leukemia inhibitory factor (lif), oncostatin m (osm), and interleukin-6 (il-6). Pretreatment with SN79 reduced METH-induced increases in CD68 and IBA-1 expression, demonstrating its ability to prevent microglial activation. SN79 also attenuated METH-induced mRNA increases in IL-6 pro-inflammatory cytokine family members. The ability of a sigma receptor antagonist to block METH-induced microglial activation and cytokine production provides a novel mechanism through which the neurotoxic effects of METH may be mitigated.

  14. 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.

  15. Can the sigma-1 receptor agonist fluvoxamine prevent schizophrenia?

    PubMed

    Hashimoto, Kenji

    2009-12-01

    In the past decade there has been increasing interest in the potential benefit of early pharmacological intervention in schizophrenia. Patients with schizophrenia show nonpsychotic and nonspecific prodromal symptoms (e.g., depression and cognitive deficits) for several years preceding the onset of frank psychosis. Several studies have demonstrated that medication with atypical antipsychotic drugs in people with prodromal symptoms may reduce the risk of subsequent transition to schizophrenia. Furthermore, a naturalistic treatment study in young people with prodromal symptoms demonstrated that medication with antidepressants could prevent the development of psychosis. Although the sample in this study was small, the results were striking. Some antidepressants, including selective serotonin reuptake inhibitors (SSRIs), had high to moderate affinities at the endoplasmic reticulum protein sigma-1 receptors, which are implicated in neuroprotection and neuronal plasticity. Among all antidepressants, fluvoxamine was the most potent sigma-1 receptor agonist. Since the effects of fluroxaming were antagonized by the selective sigma-1 receptor antagonist NE-100. Based on the role of sigma-1 receptors in the pathophysiology of cognition and depression, the author would like to propose a hypothesis that SSRIs (e.g., fluvoxamine) with sigma-1 receptor agonism may reduce the risk of subsequent transition to schizophrenia.

  16. Strings as sigma models and in the tensionless limit

    NASA Astrophysics Data System (ADS)

    Persson, Jonas

    2007-05-01

    This thesis considers two different aspects of string theory, the tensionless limit of the string and supersymmetric sigma models. The tensionless limit is used to find a IIB supergravity background generated by a tensionless string. Quantization of the tensionless string in a pp-wave background is performed and the tensionless limit is found to commute with quantization. Further, the sigma model with N=(2,2) extended world-sheet supersymmetry is considered and the requirement on the target space to have a bi-Hermitean geometry is reviewed. It is shown that the equivalence between bi-Hermitean geometry and generalized Kahler follows, in this context, from the equivalence between the Lagrangian- and Hamiltonian formulation of the model. Moreover, the explicit T-duality transformation in the Hamiltonian formulation of the sigma model is constructed and shown to be a symplectomorphism. Under certain assumptions, the amount of extended supersymmetry present in the sigma model is shown to be preserved under T-duality. Further, by requiring N=(2,2) extended supersymmetry in a first order formulation of the sigma model an intriguing geometrical structure arises and in a special case generalized complex geometry is found to be contained in the new framework.

  17. Development of Benzophenone-Alkyne Bifunctional Sigma Receptor Ligands

    PubMed Central

    Guo, Lian-Wang; Hajipour, Abdol R.; Karaoglu, Kerim; Mavlyutov, Timur A.; Ruoho, Arnold E.

    2012-01-01

    Sigma (σ) receptors represent unique non-opioid binding sites that are associated with a broad range of disease states. Sigma-2 receptors provide a promising target for diagnostic imaging and pharmacological interventions to curb tumor progression. Most recently, the progesterone receptor (PGRMC1, 25 kDa) has been identified to contain σ2 receptor-like binding properties, highlighting the need to understand the biological function of an 18-kDa protein that exhibits σ2-like photoaffinity labeling (herein denoted as σ2-18k) but the amino acid sequence of which is not known. In order to provide novel tools for the study of the σ2-18k protein, we have developed bifunctional sigma receptor ligands that bear a benzophenone photo-crosslinking moiety and an alkyne group, to which an azide-containing biotin affinity tag can be covalently attached via click chemistry following photo-crosslink. While several compounds showed favorable σ2 binding properties, compound 22 exhibited the highest affinity (2 nM) and the greatest potency in blocking photolabeling of the σ2-18k by a radioactive photoaffinity ligand. Thus, these benzophenone-alkyne sigma receptor ligands may be amenable for studying the σ2-18k protein via chemical biology approaches. To our knowledge, these compounds represent the first reported benzophenone-containing clickable sigma receptor ligands, which may potentially serve broad applications by “plugging” in various tags. PMID:23001760

  18. 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.

  19. 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.

  20. Pion-nucleon {sigma} term in lattice QCD

    SciTech Connect

    Fukugita, M.; Kuramashi, Y.; Okawa, M.; Ukawa, A.

    1995-05-01

    We calculate both the connected and disconnected contributions to the {pi}-{ital N} {sigma} term in quenched lattice QCD with the Wilson quark action on a 12{sup 3}{times}20 lattice at {beta}=5.7 with the lattice spacing {ital a}{approx}0.14 fm. The latter is evaluated with the variant wall source method, previously applied successfully for {pi}-{pi} scattering lengths and the {eta}{prime} meson mass. We found the disconnected contribution to be about twice as large as the connected one. The value for the full {pi}-{ital N} {sigma} term {sigma}=40--60 MeV is consistent with the experimental estimates. The nucleon matrix element of the strange quark density {ital {bar s}s} is fairly large in our result.

  1. 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...

  2. Establishment of a Counter-selectable Markerless Mutagenesis System in Veillonella atypica

    PubMed Central

    Zhou, Peng; Li, Xiaoli; Qi, Fengxia

    2015-01-01

    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

  3. On the Relationship Between Sigma Models and Spin Chains

    NASA Astrophysics Data System (ADS)

    Controzzi, D.; Hawkins, E.

    We consider the two-dimensional O(3) non-linear sigma model with topological term using a lattice regularization introduced by Shankar and Read [Nucl. Phys. B 336, 457 (1990)], that is suitable for studying the strong coupling regime. When this lattice model is quantized, the coefficient θ of the topological term is quantized as θ=2πs, with s integer or half-integer. We study in detail the relationship between the low energy behaviour of this theory and the one-dimensional spin-s Heisenberg model. We generalize the analysis to sigma models with other symmetries.

  4. Generalized Kähler Geometry from Supersymmetric Sigma Models

    NASA Astrophysics Data System (ADS)

    Bredthauer, Andreas; Lindström, Ulf; Persson, Jonas; Zabzine, Maxim

    2006-09-01

    We give a physical derivation of generalized Kähler geometry. Starting from a supersymmetric nonlinear sigma model, we rederive and explain the results of Gualtieri (Generalized complex geometry, DPhil thesis, Oxford University, 2004) regarding the equivalence between generalized Kähler geometry and the bi-hermitean geometry of Gates et al. (Nucl Phys B248:157, 1984). When cast in the language of supersymmetric sigma models, this relation maps precisely to that between the Lagrangian and the Hamiltonian formalisms. We also discuss topological twist in this context.

  5. Small outer-membrane lipoprotein, SmpA, is regulated by sigmaE and has a role in cell envelope integrity and virulence of Salmonella enterica serovar Typhimurium.

    PubMed

    Lewis, Claire; Skovierova, Henrieta; Rowley, Gary; Rezuchova, Bronislava; Homerova, Dagmar; Stevenson, Andrew; Sherry, Aileen; Kormanec, Jan; Roberts, Mark

    2008-03-01

    SmpA is a small outer-membrane lipoprotein that is a component of the essential YaeT outer-membrane protein assembly complex. In Salmonella enterica serovar Typhimurium (S. Typhimurium), expression of the smpA gene was shown to be directed by two promoters, smpAp1 and smpAp2. The more distal promoter, smpAp1, is dependent upon the extracytoplasmic stress response sigma factor sigma(E). An smpA null mutant was constructed in S. Typhimurium SL1344 and was shown to be more sensitive than its wild-type parent to growth at high temperature and in the presence of sodium cholate, SDS plus EDTA, and the hydrophobic antibiotic rifampicin. The lack of SmpA in S. Typhimurium elicits a sigma(E)-dependent stress response. These findings are indicative of altered outer-membrane integrity in the smpA mutant, probably due to a defect in outer-membrane protein biogenesis. SmpA was not important for entry or survival within murine macrophages; however, the S. Typhimurium smpA mutant was attenuated in mice by both the oral and parenteral routes of infection, and SmpA appeared to be most important for the growth of S. Typhimurium at systemic sites.

  6. 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.

  7. 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

  8. Voltage-gated sodium channel modulation by sigma-receptors in cardiac myocytes and heterologous systems.

    PubMed

    Johannessen, Molly; Ramachandran, Subramaniam; Riemer, Logan; Ramos-Serrano, Andrea; Ruoho, Arnold E; Jackson, Meyer B

    2009-05-01

    The sigma-receptor, a broadly distributed integral membrane protein with a novel structure, is known to modulate various voltage-gated K(+) and Ca(2+) channels through a mechanism that involves neither G proteins nor phosphorylation. The present study investigated the modulation of the heart voltage-gated Na(+) channel (Na(v)1.5) by sigma-receptors. The sigma(1)-receptor ligands [SKF-10047 and (+)-pentazocine] and sigma(1)/sigma(2)-receptor ligands (haloperidol and ditolylguanidine) all reversibly inhibited Na(v)1.5 channels to varying degrees in human embryonic kidney 293 (HEK-293) cells and COS-7 cells, but the sigma(1)-receptor ligands were less effective in COS-7 cells. The same four ligands also inhibited Na(+) current in neonatal mouse cardiac myocytes. In sigma(1)-receptor knockout myocytes, the sigma(1)-receptor-specific ligands were far less effective in modulating Na(+) current, but the sigma(1)/sigma(2)-receptor ligands modulated Na(+) channels as well as in wild type. Photolabeling with the sigma(1)-receptor photoprobe [(125)I]-iodoazidococaine demonstrated that sigma(1)-receptors were abundant in heart and HEK-293 cells, but scarce in COS-7 cells. This difference was consistent with the greater efficacy of sigma(1)-receptor-specific ligands in HEK-293 cells than in COS-7 cells. sigma-Receptors modulated Na(+) channels despite the omission of GTP and ATP from the patch pipette solution. sigma-Receptor-mediated inhibition of Na(+) current had little if any voltage dependence and produced no change in channel kinetics. Na(+) channels represent a new addition to the large number of voltage-gated ion channels modulated by sigma-receptors. The modulation of Na(v)1.5 channels by sigma-receptors in the heart suggests an important pathway by which drugs can alter cardiac excitability and rhythmicity.

  9. 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…

  10. 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…

  11. Noise Simulation of Continuous-Time {sigma}{delta} Modulators

    SciTech Connect

    Arias, J.; Quintanilla, L.; Bisbal, D.; San Pablo, J.; Enriquez, L.; Vicente, J.; Barbolla, J.

    2005-08-25

    In this work, an approach for the simulation of the effect of noise sources in the performance of continuous-time {delta}{sigma} modulators is presented. Electrical noise including thermal noise, 1/f noise and clock jitter are included in a simulation program and their impact on the system performance is analyzed.

  12. Analysis of Lean Six Sigma in the Army Contracting Process

    DTIC Science & Technology

    2011-12-01

    25 c. Lean Manufacturing ...............................................................26 d. Six Sigma...training documents and instructions. c. Lean Manufacturing The basic concept behind Lean Manufacturing systems that have been practiced for many...years in Japan are waste elimination, cost reduction and employee empowerment. Lean Manufacturing focuses on identifying and eliminating non-value

  13. SIGMA--A Graphical Approach to Teaching Simulation.

    ERIC Educational Resources Information Center

    Schruben, Lee W.

    1992-01-01

    SIGMA (Simulation Graphical Modeling and Analysis) is a computer graphics environment for building, testing, and experimenting with discrete event simulation models on personal computers. It uses symbolic representations (computer animation) to depict the logic of large, complex discrete event systems for easier understanding and has proven itself…

  14. 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…

  15. 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.

  16. 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.

  17. 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…

  18. Environmental Professional’s Guide to Lean and Six Sigma: Executive Summary

    EPA Pesticide Factsheets

    Introduction to the guide that describes how Lean and Six Sigma relate to the environment and provides guidance on how environmental professionals can connect with Lean and Six Sigma activities to generate better environmental and operational results.

  19. Sigma ligands indirectly modulate the NMDA receptor-ion channel complex on intact neuronal cells via sigma 1 site.

    PubMed

    Yamamoto, H; Yamamoto, T; Sagi, N; Klenerová, V; Goji, K; Kawai, N; Baba, A; Takamori, E; Moroji, T

    1995-01-01

    To investigate the modulatory effects of sigma ligands on the N-methyl-D-aspartate (NMDA) receptor-ion channel complex in vivo, we examined the intact cell binding of 3H-N-[1-(2-thienyl)cyclohexyl]piperidine (3H-TCP) to cultured neuronal cells prepared from fetal rat telencephalon. The 3H-TCP binding was saturable, reversible, and inhibited by a selective NMDA receptor antagonist, D-amino-5-phosphonovaleric acid. MII-limolar Mg2+ inhibited 3H-TCP binding both in the absence and presence of L-glutamate. 5-Methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate (MK801) inhibited 3H-TCP intact cell binding in a competitive manner, while haloperidol inhibited it in a noncompetitive manner. The effect of the test drugs to inhibit 3H-TCP intact cell binding was in the order of dextromethorphan, haloperidol > (+/-)MK 801 > (+)pentazocine > (-)pentazocine > DTG > PCP > (+)-N-allylnormetazocine [(+)SKF 10047] > (+)3-(3-hydroxyphenyl)-N- (1-propyl)piperidine [(+)3-PPP] > (-)SKF 10047 > (-)3-PPP. The IC50 values of the six sigma ligands for 3H-TCP binding were closely correlated with the Ki values of the corresponding drugs for DTG site 1 in the guinea pig brain reported by Rothman et al. (1991). These findings suggest that the sigma ligand indirectly modulates the NMDA receptor ion channel complex, presumably through sigma 1 sites in vivo as well as in vitro.

  20. Role of Listeria monocytogenes sigma(B) in survival of lethal acidic conditions and in the acquired acid tolerance response.

    PubMed

    Ferreira, Adriana; Sue, David; O'Byrne, Conor P; Boor, Kathryn J

    2003-05-01

    The food-borne pathogen Listeria monocytogenes can acquire enhanced resistance to lethal acid conditions through multiple mechanisms. We investigated contributions of the stress-responsive alternative sigma factor, sigma(B), which is encoded by sigB, to growth phase-dependent acid resistance (AR) and to the adaptive acid tolerance response in L. monocytogenes. At various points throughout growth, we compared the relative survival of L. monocytogenes wild-type and DeltasigB strains that had been exposed to either brain heart infusion (pH 2.5) or synthetic gastric fluid (pH 2.5) with and without prior acid adaptation. Under these conditions, survival of the DeltasigB strain was consistently lower than that of the wild-type strain throughout all phases of growth, ranging from 4 orders of magnitude less in mid-log phase to 2 orders of magnitude less in stationary phase. Survival of both DeltasigB and wild-type L. monocytogenes strains increased by 6 orders of magnitude upon entry into stationary phase, demonstrating that the L. monocytogenes growth phase-dependent AR mechanism is sigma(B) independent. sigma(B)-mediated contributions to acquired acid tolerance appear to be greatest in early logarithmic growth. Loss of a functional sigma(B) reduced the survival of L. monocytogenes at pH 2.5 to a greater extent in the presence of organic acid (100 mM acetic acid) than in the presence of inorganic acid alone (HCl), suggesting that L. monocytogenes protection against organic and inorganic acid may be mediated through different mechanisms. sigma(B) does not appear to contribute to pH(i) homeostasis through regulation of net proton movement across the cell membrane or by regulation of pH(i) buffering by the GAD system under the conditions examined in this study. In summary, a functional sigma(B) protein is necessary for full resistance of L. monocytogenes to lethal acid treatments.

  1. Sigma-1 Receptor Agonism Promotes Mechanical Allodynia After Priming the Nociceptive System with Capsaicin.

    PubMed

    Entrena, J M; Sánchez-Fernández, C; Nieto, F R; González-Cano, R; Yeste, S; Cobos, E J; Baeyens, J M

    2016-11-25

    Sigma-1 receptor antagonists promote antinociception in several models of pain, but the effects of sigma-1 agonists on nociception (particularly when the nociceptive system is primed) are not so well characterized; therefore we evaluated the effects of sigma-1 agonists on pain under different experimental conditions. The systemic administration of the selective sigma-1 agonists (+)-pentazocine and PRE-084, as well as the nonselective sigma-1 agonist carbetapentane (used clinically as an antitussive drug), did not alter sensitivity to mechanical stimulation under baseline conditions. However, they greatly promoted secondary mechanical allodynia after priming the nociceptive system with capsaicin. These effects of sigma-1 agonists were consistent in terms potency with the affinities of these drugs for sigma-1 receptors, were reversed by sigma-1 antagonists, and were not observed in sigma-1 knockout mice, indicating that they are sigma-1-mediated. Repeated systemic treatment with PRE-084 induced proallodynic effects even 24 h after treatment completion, but only after the nociceptive system was primed. However, neither the presence of this drug in the organism nor changes in sigma-1 receptor expression in areas involved in pain processing explains its long-term effects, suggesting that sustained sigma-1 agonism induces plastic changes in the nociceptive system that promote nociception.

  2. 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…

  3. 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.

  4. Sigma-1 Receptor Agonism Promotes Mechanical Allodynia After Priming the Nociceptive System with Capsaicin

    PubMed Central

    Entrena, J. M.; Sánchez-Fernández, C.; Nieto, F. R.; González-Cano, R.; Yeste, S.; Cobos, E. J.; Baeyens, J. M.

    2016-01-01

    Sigma-1 receptor antagonists promote antinociception in several models of pain, but the effects of sigma-1 agonists on nociception (particularly when the nociceptive system is primed) are not so well characterized; therefore we evaluated the effects of sigma-1 agonists on pain under different experimental conditions. The systemic administration of the selective sigma-1 agonists (+)-pentazocine and PRE-084, as well as the nonselective sigma-1 agonist carbetapentane (used clinically as an antitussive drug), did not alter sensitivity to mechanical stimulation under baseline conditions. However, they greatly promoted secondary mechanical allodynia after priming the nociceptive system with capsaicin. These effects of sigma-1 agonists were consistent in terms potency with the affinities of these drugs for sigma-1 receptors, were reversed by sigma-1 antagonists, and were not observed in sigma-1 knockout mice, indicating that they are sigma-1-mediated. Repeated systemic treatment with PRE-084 induced proallodynic effects even 24 h after treatment completion, but only after the nociceptive system was primed. However, neither the presence of this drug in the organism nor changes in sigma-1 receptor expression in areas involved in pain processing explains its long-term effects, suggesting that sustained sigma-1 agonism induces plastic changes in the nociceptive system that promote nociception. PMID:27886264

  5. 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

  6. Up-regulation of sigma(1) receptor mRNA in rat brain by a putative atypical antipsychotic and sigma receptor ligand.

    PubMed

    Zamanillo, D; Andreu, F; Ovalle, S; Pérez, M P; Romero, G; Farré, A J; Guitart, X

    2000-03-24

    Sigma(1) (sigma(1)) receptor mRNA expression was studied in the prefrontal cortex, striatum, hippocampus and cerebellum of rat brain by northern blot and in situ hybridization. The effects of a chronic treatment with antipsychotic drugs (haloperidol and clozapine), and with E-5842, a sigma(1) receptor ligand and putative atypical antipsychotic on sigma(1) receptor expression were examined. A significant increase in the levels of sigma(1) receptor mRNA in the prefrontal cortex and striatum after E-5842 administration was observed, while no apparent changes were seen with either haloperidol or clozapine. Our results suggest a long-term adaptation of the sigma(1) receptor at the level of mRNA expression in specific areas of the brain as a response to a sustained treatment with E-5842.

  7. 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

  8. A Randomized, Double-Blind Comparison of Tenofovir Alafenamide (TAF) vs. Tenofovir Disoproxil fumarate (TDF), Each Coformulated with Elvitegravir, Cobicistat, and Emtricitabine (E/C/F) for Initial HIV-1 Treatment: Week 144 Results.

    PubMed

    Arribas, José R; Thompson, Melanie; Sax, Paul E; Haas, Bernhard; McDonald, Cheryl; Wohl, David A; DeJesus, Edwin; Clarke, Amanda E; Guo, Susan; Wang, Hui; Callebaut, Christian; Plummer, Andrew; Cheng, Andrew; Das, Moupali; McCallister, Scott

    2017-03-09

    In two double-blind Phase 3 trials, 1733 antiretroviral-naïve adults were randomized to tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), each coformulated with elvitegravir/cobicistat/emtricitabine (E/C/F). At 144 weeks, TAF was superior to TDF in virologic efficacy, with 84.2% vs. 80.0% having HIV-1 RNA <50 copies/mL (difference 4.2%; 95%CI 0.6% to 7.8%). TAF had less impact than TDF on bone mineral density and renal biomarkers. No participants on TAF had renal-related discontinuations vs 12 on TDF (P<0.001), with no cases of proximal tubulopathy for TAF vs 4 for TDF. There were greater increases in lipids with TAF vs. TDF, with no difference in the total cholesterol to high density lipoprotein ratio. For initial HIV therapy, E/C/F/TAF is superior to E/C/F/TDF in efficacy and bone and renal safety.

  9. 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.

  10. Vacuum Properties of the {Sigma}(1385){sup +} Resonance

    SciTech Connect

    Epple, E.

    2011-10-21

    We present data taken employing a proton beam incident on a liquid hydrogen target with a kinetic energy of 3.5 GeV. A total statistics of {approx_equal} 1.2.10{sup 9} events was collected by the High Acceptance Di-Electron Spectrometer (HADES) and analysed to study the properties of the {Sigma}(1385){sup +}-resonance. A clear signal corresponding to a peak of the Breit-Wigner parametrization of M = 1382.98{+-}0.79MeV/c{sup 2} and a width of {Gamma}{sub 0} = 38.78{+-}2.03 MeV/c{sup 2} was extracted. The investigation of the differential production cross- section shows a strong anisotropy in the angular distribution of the {Sigma}(1385){sup +}-hyperon with respect to the beam direction in p+p collisions.

  11. New observations with the gamma ray imager SIGMA

    NASA Technical Reports Server (NTRS)

    Roques, J. P.; Vedrenne, G.

    1992-01-01

    Results from the use of the gamma ray telescope SIGMA are given. An identification and an extensive study was done of sources contributing to the emission of the Galactic center region above 30 keV. A strong line was observed at 480 keV from Nova Muscae, which may be interpreted as an annihilation line with a redshift due to the presence of a compact object. The soft x-ray tails observed by SIGMA in some transient sources already identified as soft x-ray transients might be a common characteristic of these objects and has to be explained. The unusual spectrum of NGC4151 with a break around 50 keV can characterize a particular state of this kind of object. If it is the case, it has interesting implications for the origin of the Cosmic Diffuse Background.

  12. 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.

  13. Scalar mesons in three-flavor linear sigma models

    SciTech Connect

    Deirdre Black; Amir H. Fariborz; Sherif Moussa; Salah Nasri; Joseph Schrechter

    2001-09-01

    The three flavor linear sigma model is studied in order to understand the role of possible light scalar mesons in the pi-pi, pi-K and pi-eta elastic scattering channels. The K-matrix prescription is used to unitarize tree-level amplitudes and, with a sufficiently general model, we obtain reasonable ts to the experimental data. The effect of unitarization is very important and leads to the emergence of a nonet of light scalars, with masses below 1 GeV. We compare with a scattering treatment using a more general non-linear sigma model approach and also comment upon how our results t in with the scalar meson puzzle. The latter involves a preliminary investigation of possible mixing between scalar nonets.

  14. Generalized complex geometry, generalized branes and the Hitchin sigma model

    NASA Astrophysics Data System (ADS)

    Zucchini, Roberto

    2005-03-01

    Hitchin's generalized complex geometry has been shown to be relevant in compactifications of superstring theory with fluxes and is expected to lead to a deeper understanding of mirror symmetry. Gualtieri's notion of generalized complex submanifold seems to be a natural candidate for the description of branes in this context. Recently, we introduced a Batalin-Vilkovisky field theoretic realization of generalized complex geometry, the Hitchin sigma model, extending the well known Poisson sigma model. In this paper, exploiting Gualtieri's formalism, we incorporate branes into the model. A detailed study of the boundary conditions obeyed by the world sheet fields is provided. Finally, it is found that, when branes are present, the classical Batalin-Vilkovisky cohomology contains an extra sector that is related non trivially to a novel cohomology associated with the branes as generalized complex submanifolds.

  15. 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.

  16. 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.

  17. Digital pixel sensor array with logarithmic delta-sigma architecture.

    PubMed

    Mahmoodi, Alireza; Li, Jing; Joseph, Dileepan

    2013-08-16

    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.

  18. Multiharmonic tracking using sigma-point Kalman filter.

    PubMed

    Kim, Sunghan; Paul, Anindya S; Wan, Eric A; McNames, James

    2008-01-01

    Several groups have proposed the state-space approach to track time-varying frequencies ofmulti-harmonic quasi-periodic signals contaminated with white Gaussian noise. We compared the extended Kalman filter (EKF) and sigma-point Kalman filter (SPKF) algorithms on this problem. On average, the SPKF outperformed the EKF and more accurately tracked the instantaneous frequency over a wide range of signal-to-noise (SNR) ratios.

  19. 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.

  20. Lean Six Sigma for Reduced Cycle Costs and Improved Readiness

    DTIC Science & Technology

    2006-09-30

    and/or training) increases the cycle-time, which in turn decreases readiness, Ao. Therefore, the warfighters are J3-= forced to satisfy mission...technique that aims to develop and deliver near- perfect products and services. The primary goal of Six Sigma is to improve customer satisfaction (and...thereby, profitability) by reducing and eliminating defects. In this case, the defects may be related to any aspect of customer satisfaction

  1. Comparing Poisson Sigma Model with A-model

    NASA Astrophysics Data System (ADS)

    Bonechi, F.; Cattaneo, A. S.; Iraso, R.

    2016-10-01

    We discuss the A-model as a gauge fixing of the Poisson Sigma Model with target a symplectic structure. We complete the discussion in [4], where a gauge fixing defined by a compatible complex structure was introduced, by showing how to recover the A-model hierarchy of observables in terms of the AKSZ observables. Moreover, we discuss the off-shell supersymmetry of the A-model as a residual BV symmetry of the gauge fixed PSM action.

  2. A symmetric approach to the massive nonlinear sigma model

    DOE PAGES

    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.

  3. 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.

  4. The nature of the [20.0] 1Sigma+ electronic state of RhB: a multiconfigurational study.

    PubMed

    Gobbo, João Paulo; Borin, Antonio Carlos

    2007-01-07

    Multiconfigurational second order perturbation theory, with extended atomic basis sets and inclusion of scalar relativistic effects, was employed to investigate the low-lying (1)Sigma(+) electronic states of RhB. The [20.0] (1)Sigma(+) state is represented by a single configuration, mid R:[ellipsis (horizontal)]10sigma(2)11sigma(1)5pi(4)2delta(4)12sigma(1), derived from a single excitation (11sigma-->12sigma) from the ground state, which defines its electronic nature. A new excited state, coined as [9.0] (1)Delta (R(0)=1.786A, DeltaG(12)=792 cm(-1)), located 9221 cm(-1) above the X(1)Sigma(+) state, and described by the |...10sigma(2)11sigma(2)5pi(4)2delta(3)12sigma(1)> electronic configuration, was also identified.

  5. 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.

  6. Sigma virus and male reproductive success in Drosophila melanogaster

    PubMed Central

    Pattanaik, Swetapadma; Johnson, Laura; Matos, Luis F.; Brusini, Jérémie; Wayne, Marta L.

    2016-01-01

    The risk of disease transmission can affect female mating rate, and thus sexual conflict. Furthermore, the interests of a sexually transmitted organism may align or diverge with those of either sex, potentially making the disease agent a third participant in the sexual arms race. In Drosophila melanogaster, where sexual conflict over female mating rate is well established, we investigated how a common, non-lethal virus (sigma virus) might affect this conflict. We gave uninfected females the opportunity to copulate twice in no-choice trials: either with two uninfected males, or with one male infected with sigma virus followed by an uninfected male. We assessed whether females respond behaviorally to male infection, determined whether male infection affects either female or male reproductive success, and measured offspring infection rates. Male infection status did not influence time to copulation, or time to re-mating. However, male infection did affect male reproductive success: first males sired a significantly greater proportion of offspring, as well as more total offspring, when they were infected with sigma virus. Thus viral infection may provide males an advantage in sperm competition, or, possibly, females may preferentially use infected sperm. We found no clear costs of infection in terms of offspring survival. Viral reproductive success (the number of infected offspring) was strongly correlated with male reproductive success. Further studies are needed to demonstrate whether virus-induced changes in reproductive success affect male and female lifetime fitness, and whether virus-induced changes are under male, female, or viral control. PMID:27616808

  7. 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.

  8. Resolving the Critical Ambiguities of the M-Sigma Relation

    NASA Astrophysics Data System (ADS)

    Batcheldor, Daniel

    2006-07-01

    Determining the best estimates of the masses of supermassive black holes {SMBHs} and their uncertainties is crucial for constraining the slope and scatter of the SMBH mass vs. stellar velocity dispersion {M-sigma} relation and for understanding the relation between SMBHs and their host galaxies. We propose to critically evaluate the values of the SMBH masses in a sample of 23 galaxies using data derived from STIS long-slit spectroscopy. This study will directly achieve three significant and fundamental improvements to the M-sigma relation. First, we will use all suitable STIS long-slit data to analyze SMBH masses in an entirely homogeneous fashion. Second, we will substantially increase the SMBH sample size with new estimates. Finally, we will use our state-of-the-art Schwarzschild code, which will, for the first time and independently of the modelling parameters, explore the full range of SMBH masses that give statistically acceptable fits to a given data set. These analyses can be carried out with unrivaled efficiency using the cutting-edge computing facilities available at RIT. This work will result in the most accurate and reliable estimate of the form {slope and scatter} of the M-sigma relation; to date improvements have only been somewhat incremental. Such a study will place important constraints on some of the most fundamental problems remaining in contemporary astrophysics.

  9. 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.

  10. Precision measurement of the {Sigma}{sup 0} hyperon mass

    SciTech Connect

    Wang, M.H.L.S.; Hartouni, E.P.; Kreisler, M.N.

    1998-02-17

    The research that is described in this paper is part of a program to study strong interaction mechanisms in proton proton collisions. The program consists of two experiments: Brookhaven E766 in which we studied the reactions pp {yields} p+ all charged particles with 27.5 GeV/c incident protons and Fermilab E690 in which we studied the reactions pp {yields} p+ all charged particles with 800 GeV/c incident protons. In these experiments, we employed state-of-the-art data acquisition sys- tems and acquired large samples of data: at Brookhaven we amassed 300 million high multiplicity events and at Fermilab, 5.5 billion events. Our uncertainty in the {Sigma}{sup 0} mass is more than 7 times smaller than the best previous result and was based on 16 times the statistics. Likewise, the {Sigma}{sup 0} - {Lambda}{sup 0} mass difference is more than 14 times more accurate than the previous best result. Finally, we note that this measurement is the first direct measurement of the {Sigma}{sup 0} mass.

  11. 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.

  12. Sigma receptor ligands: possible application as therapeutic drugs and as radiopharmaceuticals.

    PubMed

    Hashimoto, Kenji; Ishiwata, Kiichi

    2006-01-01

    Sigma receptors are classified into sigma(1) and sigma(2) subtypes. These subtypes display a different tissue distribution and a distinct physiological and pharmacological profile in the central and peripheral nervous system. The characterization of these subtypes and the discovery of new specific sigma receptor ligands demonstrated that sigma receptors are novel targets for the therapeutic treatment of neuropsychiatric diseases (schizophrenia, depression, and cognition), brain ischemia, and cocaine addiction. Furthermore, imaging of sigma(1) receptors in the human brain using specific PET radioligands has started. In addition, the two sigma receptor subtypes are also expressed on tumor cells, where they could be of prognostic relevance. The ability of sigma(2) receptor agonists to inhibit tumor cell proliferation through mechanisms that might involve apoptosis, intracellular Ca(2+), and sphingolipids has promoted the development of sigma(2) receptor agonists as novel therapeutic drugs for treating cancer. Consequently, sigma(2) receptor ligands have been demonstrated to be potentially useful tumor imaging ligands. In this article, we focus on the sigma receptor ligands as therapeutic agents and as radiopharmaceuticals.

  13. 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.

  14. IL-10 mediates sigma 1 receptor-dependent suppression of antitumor immunity.

    PubMed

    Zhu, Li X; Sharma, Sherven; Gardner, Brian; Escuadro, Brian; Atianzar, Kimberly; Tashkin, Donald P; Dubinett, Steven M

    2003-04-01

    Sigma receptors are unique endoplasmic reticulum proteins that mediate signaling for a variety of drugs. We determined the effect of sigma(1) receptor agonists on immune responses in a syngeneic lung cancer model. Sigma(1) receptor agonists, including cocaine, up-regulated splenocyte IL-10 mRNA and protein production in vitro in a sigma receptor-dependent, pertussis toxin-sensitive manner. In vivo, sigma(1) receptor agonists promoted tumor growth and induced IL-10 at the tumor site. Increased tumor growth was prevented by administration of specific Abs to IL-10 or by administration of specific sigma(1) receptor antagonists. We report that sigma(1) receptor ligands, including cocaine, augment tumor growth through an IL-10 dependent mechanism.

  15. 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.

  16. 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.

  17. Using lean Six Sigma to improve hospital based outpatient imaging satisfaction.

    PubMed

    McDonald, Angelic P; Kirk, Randy

    2013-01-01

    Within the hospital based imaging department at Methodist Willowbrook, outpatient, inpatient, and emergency patients are all performed on the same equipment with the same staff. The critical nature of the patient is the deciding factor as to who gets done first and in what order procedures are performed. After an aggressive adoption of Intentional Tools, the imaging department was finally able to move from a two year mean Press Ganey, outpatient satisfaction average score of 91.2 and UHC percentile ranking of 37th to a mean average of 92.1 and corresponding UHC ranking of 60th percentile. It was at the 60th percentile ranking that the department flat lined. Using the Six Sigma DMAIC process, opportunity for further improvement was identified. A two week focus pilot was conducted specifically on areas identified through the Six Sigma process. The department was able to jump to 88th percentile ranking and a mean of 93.7. With pay for performance focusing on outpatient satisfaction and a financial incentive to improving and maintaining the highest scores, it was important to know where the imaging department should apply its financial resources to obtain the greatest impact.

  18. 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.

  19. CREB decreases astrocytic excitability by modifying subcellular calcium fluxes via the sigma-1 receptor.

    PubMed

    Eraso-Pichot, A; Larramona-Arcas, R; Vicario-Orri, E; Villalonga, R; Pardo, L; Galea, E; Masgrau, R

    2017-03-01

    Astrocytic excitability relies on cytosolic calcium increases as a key mechanism, whereby astrocytes contribute to synaptic transmission and hence learning and memory. While it is a cornerstone of neurosciences that experiences are remembered, because transmitters activate gene expression in neurons, long-term adaptive astrocyte plasticity has not been described. Here, we investigated whether the transcription factor CREB mediates adaptive plasticity-like phenomena in astrocytes. We found that activation of CREB-dependent transcription reduced the calcium responses induced by ATP, noradrenaline, or endothelin-1. As to the mechanism, expression of VP16-CREB, a constitutively active CREB mutant, had no effect on basal cytosolic calcium levels, extracellular calcium entry, or calcium mobilization from lysosomal-related acidic stores. Rather, VP16-CREB upregulated sigma-1 receptor expression thereby increasing the release of calcium from the endoplasmic reticulum and its uptake by mitochondria. Sigma-1 receptor was also upregulated in vivo upon VP16-CREB expression in astrocytes. We conclude that CREB decreases astrocyte responsiveness by increasing calcium signalling at the endoplasmic reticulum-mitochondria interface, which might be an astrocyte-based form of long-term depression.

  20. L(p) approximation capabilities of sum-of-product and sigma-pi-sigma neural networks.

    PubMed

    Long, Jinling; Wu, Wei; Nan, Dong

    2007-10-01

    This paper studies the L(p) approximation capabilities of sum-of-product (SOPNN) and sigma-pi-sigma (SPSNN) neural networks. It is proved that the set of functions that are generated by the SOPNN with its activation function in $L_{loc};p(\\mathcal{R})$ is dense in $L;p(\\mathcal{K})$ for any compact set $\\mathcal{K}\\subset \\mathcal{R};N$, if and only if the activation function is not a polynomial almost everywhere. It is also shown that if the activation function of the SPSNN is in ${L_{loc};\\infty(\\mathcal{R})}$, then the functions generated by the SPSNN are dense in $L;p(\\mathcal{K})$ if and only if the activation function is not a constant (a.e.).

  1. Azimuthal asymmetry as a new handle on {sigma}{sub L}/{sigma}{sub T} in diffractive DIS

    SciTech Connect

    Nikolaev, N.N. |; Pronyaev, A.V.; Zakharov, B.G.

    1999-05-01

    We propose a new method of determining R{sup D}={sigma}{sub L}{sup D}/{sigma}{sub T}{sup D} from the dependence of the diffractive cross section on the azimuthal angle between the electron scattering and proton scattering planes. The method is based on our finding of the model independence of the ratio of the LT interference and transverse diffractive structure functions. The predicted azimuthal asymmetry is substantial and can be measured at DESY HERA. We show that the accuracy of our reconstruction of R{sup D} is adequate for a reliable test of an important PQCD prediction of R{sup D}{approx_gt}1 for large {beta}. {copyright} {ital 1999} {ital The American Physical Society}

  2. Comparison of binding parameters of sigma 1 and sigma 2 binding sites in rat and guinea pig brain membranes: novel subtype-selective trishomocubanes.

    PubMed

    Nguyen, V H; Kassiou, M; Johnston, G A; Christie, M J

    1996-09-12

    Comparisons of binding parameters of [3H](+)-pentazocine and [3H]1,3-di-o-tolylguanidine (DTG) at sigma binding sites in guinea pig and rat brain membranes demonstrated that [3H](+)-pentazocine binds to a single high-affinity site, whereas [3H]DTG binds to two high-affinity sites in both species. The Kd values of the radioligands were similar in both types of membranes. However, the density of sigma 1 sites in guinea pig was significantly higher than that of rat. Novel trishomocubanes were tested for their affinities at sigma 1 and sigma 2 binding sites in guinea pig brain membranes using [3H](+)-pentazocine and [3H]DTG as the radioligands. N-(4-Phenylbutyl)-3-hydroxy-4- azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecane (ANSTO-14) showed the highest affinity for the sigma 1 site (Ki = 9.4 nM) and 19-fold sigma 1/sigma 2 selectivity, as a result of increasing the alkyl chain between the cubane moiety and the aromatic ring. N-(3'-Fluorophenyl)methyl- 3-hydroxy-4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11]dodeca ne (ANSTO-19), displayed the highest affinity for sigma 2 sites (Ki = 19.6 nM) and 8-fold sigma 2/sigma 1 selectivity due to a fluoro substitution in the meta position of the aromatic ring. These represent structurally novel lead compounds, especially for the development of selective sigma 2 receptor ligands.

  3. Sigma-1 receptors (sigma(1) binding sites) form raft-like microdomains and target lipid droplets on the endoplasmic reticulum: roles in endoplasmic reticulum lipid compartmentalization and export.

    PubMed

    Hayashi, Teruo; Su, Tsung-Ping

    2003-08-01

    The brain sigma-1 receptors can bind neurosteroids and psychotropic drugs, including neuroleptics and cocaine and are implicated in schizophrenia, depression, and drug dependence. In this study, we found that sigma-1 receptors specifically target lipid storage sites (lipid droplets) on the endoplasmic reticulum by forming a distinct class of lipid microdomains. Both endogenously expressing sigma-1 receptors and transfected C-terminally enhanced yellow fluorescent protein (EYFP)-tagged sigma-1 receptors (Sig-1R-EYFP) target unique "ring-like" structures associated with endoplasmic reticulum reticular networks in NG108-15 cells. The ring-like structures contain neutral lipids and are enlarged by the oleate treatment, indicating that they are endoplasmic reticulum-associated lipid droplets (ER-LDs). sigma-1 receptors colocalize with caveolin-2, a cholesterol-binding protein in lipid rafts on the ER-LDs, but not with adipocyte differentiation-related protein (ADRP), a cytosolic lipid droplet (c-LD)-specific protein. When the double-arginine ER retention signal on the N terminus of sigma-1 receptors is truncated, sigma-1 receptors no longer exist on ER-LDs, but predominantly target c-LDs, which contain ADRP. sigma-1 receptors on ER-LDs form detergent-resistant raft-like lipid microdomains, the buoyancy of which is different from that of plasma membrane lipid rafts. (+)-Pentazocine causes sigma-1 receptors to disappear from the microdomains. N-Terminally EYFP-tagged sigma-1 receptors (EYFP-Sig-1R) failed to target ER-LDs. EYFP-Sig-1R-transfected cells showed an unrestricted distribution of neutral lipids all over the endoplasmic reticulum network, decreases in c-LDs and cholesterol in plasma membranes, and the bulbous aggregation of endoplasmic reticulum. Thus, sigma-1 receptors are unique endoplasmic reticulum proteins that regulate the compartmentalization of lipids on the endoplasmic reticulum and their export from the endoplasmic reticulum to plasma membrane and c-LDs.

  4. The Sigma B operon is a determinant of fitness for a Listeria monocytogenes serotype 4b strain in soil.

    PubMed

    Gorski, Lisa; Duhé, Jessica M; Flaherty, Denise

    2011-06-01

    In nature the foodborne pathogen Listeria monocytogenes lives as a saprophyte where it can contaminate preharvest produce. This environment can present many stresses such as ultraviolet light, variations in temperature and humidity, and oxidative stress from growing plant matter in the soil. The alternative sigma factor Sigma B, encoded by sigB, controls the response to most stresses in L. monocytogenes. Fitness in soil and on radishes sown and grown in contaminated soil was measured in a wild-type and an isogenic sigB operon mutant strain to determine if the sigma factor was necessary for life in these niches. Levels of wild-type and mutant strains were monitored in contaminated soil over the course of radish gestation from seed to mature tuber, and levels on mature radishes were determined. The wild-type strain was able to survive in soil over the 4 weeks of the experiment at levels of 4-7 log CFU/g soil, and the levels of the sigB mutant were reduced by 1-2 log from the wild type. The mutant showed reduced levels in soil by 6 h after inoculation, which was partially recovered when the mutant was complemented, and stayed at a reduced level over the next 4 weeks. Upon harvest, 3-4 log CFU/g of wild-type L. monocytogenes was detected on radish surfaces, and the bacteria could not be washed off under running water. On mature radishes populations of the mutant strain were 1-2 log CFU/g lower than the wild type. The levels on mature radishes reflected the levels in the soil at 4 weeks. The conclusions are that the Sigma B operon is necessary for initial adaptation to the soil environment, and plays a role in maintaining the population, but does not play a role in attachment or colonization of the radish.

  5. 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.

  6. Measurements of sigma (V + D*)/sigma( V) in 9:7 FB-1 at CDF Run II

    NASA Astrophysics Data System (ADS)

    Matera, Keith

    The Standard Model of particle physics has been remarkably successful, but the non-perturbative features of quantum chromodynamics must be tested and modeled with data. There have been many such tests, focused primarily on the use of jet-based probes of heavy flavor (bottom and charm quark) production at hadron colliders. In this thesis, we propose and test a strategy for identifying heavy flavor in events containing a W or Z vector boson (a V boson); this technique probes a much lower energy regime than can be explored by jet-based methods. In a sample of W and Z events skimmed from 9.7 fb-1 of high-pT electron and muon data from CDF Run II pp¯ collisions at center of mass energy sqrt(s) = 1.96 GeV, we identify charm by fully reconstructing D*(2010) → D0(→ Kpi)pis decays at the track level. Using a binned fit of Deltam = m(Kpipis) - m(Kpi) to count reconstructed D* candidates, we then unfold these raw counts with acceptance values derived from Monte Carlo, and present measurements of sigma(W + D*)/sigma(W) and sigma(Z + D*)/sigma(Z) in the W/Z leptonic decay channels. All measurements are found to be in agreement with the predictions of Pythia 6.2 (PDF set CTEQ5L). These results include the first measurement of W/Z + c production in events with zero jet objects at the Tevatron, and the first measurement of W/Z + c production with p T(c) < 15 GeV at the Tevatron.

  7. 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.

  8. Sigma-1 receptor ligands: potential in the treatment of neuropsychiatric disorders.

    PubMed

    Hayashi, Teruo; Su, Tsung-Ping

    2004-01-01

    The sigma receptor was originally proposed to be a subtype of the opioid receptor. However, it is now clear that sigma receptors are unique non-opioid, non-phencyclidine brain proteins. Two types of sigma receptor exist, the sigma-1 receptor and the sigma-2 receptor. sigma-1 receptors have been cloned and their distribution, physiological functions and roles in signal transduction were recently characterised. Certain sex hormones in the brain (neurosteroids) are known to interact with sigma-1 receptors. sigma-1 receptors regulate glutamate NMDA receptor function and the release of neurotransmitters such as dopamine. They are thus proposed to be involved in learning and memory as well as in certain neuropsychiatric disorders. Selective sigma-1 receptor ligands have been suggested to represent a new class of therapeutic agents for neuropsychiatric disorders, although none have yet been introduced into therapeutic use. Early studies showed that psychotomimetic benzomorphans, as well as several antipsychotics, can bind to sigma-1 receptors. As a result of these findings, sigma-1 receptor ligands have been proposed as being of potential use in the treatment of schizophrenia. Nevertheless, the relationship of sigma-1 receptors to the underlying pathogenesis of schizophrenia is still unclear. sigma-1 receptor ligands have failed to improve acute psychotic symptoms of schizophrenia in clinical trials, but, interestingly, a few studies have shown an improvement in negative symptoms in schizophrenic patients. A number of preclinical studies have shown that selective agonists of sigma-1 receptors affect higher-ordered brain functions such as learning and memory, cognition and mood. These studies indicate that sigma-1 receptor agonists may exert therapeutic effects in depression and senile dementia. Indeed, the sigma-1 receptor agonist igmesine, has been shown to improve depression in a clinical trial. The most distinctive feature of the action of sigma-1 receptor ligands is

  9. 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.

  10. Synchrotron Based Observations of Sigma Phase Formation and Dissolution in Duplex Stainless Steel

    SciTech Connect

    Elmer, J; Palmer, T; Specht, E

    2006-08-22

    The formation and growth of sigma ({sigma}) phase in 2205 duplex stainless steel was observed and measured in real time using synchrotron radiation during isothermal heat treating at temperatures between 700 C and 850 C. Synchrotron experiments were performed on this material at the Advanced Photon Source (APS) while isothermally holding the samples for times of up to 10 hr. During the isothermal hold, sigma formed in quantities up to 22% as the ferrite transformed to a mixture of sigma and austenite phases. In addition, sigma formed at 850 C was heated to 1000 C to observe its dissolution. The amounts of sigma that formed, and the dissolution temperature of sigma were compared to the results predicted by Thermocalc, showing differences between the calculated and measured values. The synchrotron data was further modeled using a modified Johnson-Mehl-Avrami analysis to determine kinetic parameters for sigma formation. The initial JMA exponent, n, at low fractions of sigma was found to be approximately 7.0, however, towards the end of the transformation, n decreased to values of approximately 0.75. Because of the variable value of n, it was not possible to determine reliable values for the activation energy and pre-exponential terms for the JMA equation. During cooling to room temperature, the high temperature austenite partially transformed to ferrite, substantially increasing the ferrite content while the sigma phase kept its high temperature value.

  11. sigma Receptor activation blocks potassium channels and depresses neuroexcitability in rat intracardiac neurons.

    PubMed

    Zhang, Hongling; Cuevas, Javier

    2005-06-01

    The sigma receptors have been implicated in the regulation of the cardiovascular system, and sigma-1 receptor transcripts have been found in parasympathetic intracardiac neurons. However, the cellular function of sigma-1 receptors in these cells remains to be determined. Effects of sigma receptor activation on voltage-activated K(+) channels and action potential firing were studied in isolated intracardiac neurons using whole-cell patch-clamp recording techniques. Activation of sigma receptors reversibly blocked delayed outwardly rectifying potassium channels, large conductance Ca(2+)-sensitive K(+) channels, and the M-current with maximal inhibition >80%. The inhibition of K(+) channels by sigma ligands was dose-dependent, and the rank order potency of (+)-pentazocine > ibogaine > 1,3-di-O-tolyguanidin (DTG) suggests that the effect is mediated by sigma-1 receptor activation. Preincubation of neurons with the irreversible sigma receptor antagonist metaphit blocked DTG-induced inhibition of K(+) channels, confirming that the effect is mediated by sigma receptor activation. Although bath application of sigma ligands depolarized intracardiac neurons, the number of action potentials fired by the cells in response to depolarizing current pulses was decreased in the presence of these drugs. Neither dialysis of the neurons nor application of intracellular 5'-O-(2-thiodiphosphate) trilithium salt inhibited the effect of sigma receptors on K(+) channels, which suggests that the signal transduction pathway does not involve a diffusible cytosolic second messenger or a G protein. Together, these data suggest that sigma-1 receptors are directly coupled to K(+) channels in intracardiac neurons. Furthermore, activation of sigma-1 receptors depresses the excitability of intracardiac neurons and is thus likely to block parasympathetic input to the heart.

  12. 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.

  13. Inhibitory activity for the interferon-induced protein kinase is associated with the reovirus serotype 1 sigma 3 protein.

    PubMed Central

    Imani, F; Jacobs, B L

    1988-01-01

    In this report we demonstrate that reovirus serotype 1-infected cells contain an inhibitor of the interferon-induced, double-stranded RNA (dsRNA)-dependent protein kinase. We provide evidence that suggests that the virus-encoded sigma 3 protein is likely responsible for this kinase inhibitory activity. We could not detect activation of the dsRNA-dependent protein kinase in extracts prepared from either interferon-treated or untreated reovirus serotype 1-infected mouse L cells under conditions that led to activation of the kinase in extracts prepared from either interferon-treated or untreated, uninfected cells. Extracts from reovirus-infected cells blocked activation of kinase in extracts from interferon-treated cells when the two were mixed prior to assay. The kinase inhibitory activity in extracts of reovirus-infected cells could be overcome by adding approximately 100-fold excess of dsRNA over the amount required to activate kinase in extracts of uninfected cells. Kinase inhibitory activity in extracts of interferon-treated, virus-infected cells could be overcome with somewhat less dsRNA (approximately 10-fold excess). Most of the inhibitory activity in the extracts could be removed by adsorption with immobilized anti-reovirus sigma 3 serum or immobilized dsRNA, suggesting that the dsRNA-binding sigma 3 protein is necessary for kinase inhibitory activity. Purified sigma 3 protein, when added to reaction mixtures containing partially purified kinase, inhibited enzyme activation. Control of activation of this kinase, which can modify eukaryotic protein synthesis initiation factor 2, may be relevant to the sensitivity of reovirus replication to treatment of cells with interferon and to the shutoff of host protein synthesis in reovirus-infected cells. Images PMID:2460857

  14. Inverse magnetic catalysis in the linear sigma model

    NASA Astrophysics Data System (ADS)

    Ayala, A.; Loewe, M.; Zamora, R.

    2016-05-01

    We compute the critical temperature for the chiral transition in the background of a magnetic field in the linear sigma model, including the quark contribution and the thermo-magnetic effects induced on the coupling constants at one loop level. For the analysis, we go beyond mean field aproximation, by taking one loop thermo-magnetic corrections to the couplings as well as plasma screening effects for the boson's masses, expressed through the ring diagrams. We found inverse magnetic catalysis, i.e. a decreasing of the critical chiral temperature as function of the intensity of the magnetic field, which seems to be in agreement with recent results from the lattice community.

  15. 3D Loop Models and the CPn-1 Sigma Model

    NASA Astrophysics Data System (ADS)

    Nahum, Adam; Chalker, J. T.; Serna, P.; Ortuño, M.; Somoza, A. M.

    2011-09-01

    Many statistical mechanics problems can be framed in terms of random curves; we consider a class of three-dimensional loop models that are prototypes for such ensembles. The models show transitions between phases with infinite loops and short-loop phases. We map them to CPn-1 sigma models, where n is the loop fugacity. Using Monte Carlo simulations, we find continuous transitions for n=1, 2, 3, and first order transitions for n≥5. The results are relevant to line defects in random media, as well as to Anderson localization and (2+1)-dimensional quantum magnets.

  16. SigmaB-dependent and sigmaB-independent mechanisms contribute to transcription of Listeria monocytogenes cold stress genes during cold shock and cold growth.

    PubMed

    Chan, Yvonne C; Boor, Kathryn J; Wiedmann, Martin

    2007-10-01

    The role of the stress response regulator sigma(B) (encoded by sigB) in directing the expression of selected putative and confirmed cold response genes was evaluated using Listeria monocytogenes 10403S and an isogenic DeltasigB mutant, which were either cold shocked at 4 degrees C in brain heart infusion (BHI) broth for up to 30 min or grown at 4 degrees C in BHI for 12 days. Transcript levels of the housekeeping genes rpoB and gap, the sigma(B)-dependent genes opuCA and bsh, and the cold stress genes ltrC, oppA, and fri were measured using quantitative reverse transcriptase PCR. Transcriptional start sites for ltrC, oppA, and fri were determined using rapid amplification of cDNA ends PCR. Centrifugation was found to rapidly induce sigma(B)-dependent transcription, which necessitated the use of centrifugation-independent protocols to evaluate the contributions of sigma(B) to transcription during cold shock. Our data confirmed that transcription of the cold stress genes ltrC and fri is at least partially sigma(B) dependent and experimentally identified a sigma(B)-dependent ltrC promoter. In addition, our data indicate that (i) while sigma(B) activity is induced during 30 min of cold shock, this cold shock does not induce the transcription of sigma(B)-dependent or -independent cold shock genes; (ii) sigma(B) is not required for L. monocytogenes growth at 4 degrees C in BHI; and (iii) transcription of the putative cold stress genes opuCA, fri, and oppA is sigma(B) independent during growth at 4 degrees C, while both bsh and ltrC show growth phase and sigma(B)-dependent transcription during growth at 4 degrees C. We conclude that sigma(B)-dependent and sigma(B)-independent mechanisms contribute to the ability of L. monocytogenes to survive and grow at low temperatures.

  17. Evaluation of Rutter Sigma S6 Ice Navigation Radar on USCGC Healy during Arctic Shield 2014

    DTIC Science & Technology

    2015-03-01

    determine if the Sigma S6 processor is an improvement upon current radar processing capabilities. Data were collected simultaneously from both radar...system was evaluated. The Sigma S6 radar processor in the Ice Navigation radar system is unique in that it processes a full dynamic range of data (12...Sigma 6 processor and a hand-held camera to record CG radar display data . Photographs, videos and other environmental data will be collected through

  18. A Multiple-Case Analysis of Lean Six Sigma Deployment and Implementation Strategies

    DTIC Science & Technology

    2005-03-01

    Limitations of the Research This scope of this research is limited to the deployment and implementation phase of the Lean Six Sigma methodology in private...implementing an integrated Lean Six Sigma methodology . A cross-case synthesis technique was then used to analyze the collected data. This...Lean Six Sigma methodology . Lean Lean is commonly understood in manufacturing to be the elimination of waste from a process in order to

  19. Nonlinear sigma models with compact hyperbolic target spaces

    SciTech Connect

    Gubser, Steven; Saleem, Zain H.; Schoenholz, Samuel S.; Stoica, Bogdan; Stokes, James

    2016-06-23

    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. In conclusion, 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.

  20. Nonlinear sigma models with compact hyperbolic target spaces

    DOE PAGES

    Gubser, Steven; Saleem, Zain H.; Schoenholz, Samuel S.; ...

    2016-06-23

    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 themore » 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. In conclusion, 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.« less

  1. 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

  2. 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.

  3. 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.

  4. EBSD spatial resolution for detecting sigma phase in steels.

    PubMed

    Bordín, S Fernandez; Limandri, S; Ranalli, J M; Castellano, G

    2016-12-01

    The spatial resolution of the electron backscatter diffraction signal is explored by Monte Carlo simulation for the sigma phase in steel at a typical instrumental set-up. In order to estimate the active volume corresponding to the diffracted electrons, the fraction of the backscattered electrons contributing to the diffraction signal was inferred by extrapolating the Kikuchi pattern contrast measured by other authors, as a function of the diffracted electron energy. In the resulting estimation, the contribution of the intrinsic incident beam size and the software capability to deconvolve patterns were included. A strong influence of the beam size on the lateral resolution was observed, resulting in 20nm for the aperture considered. For longitudinal and depth directions the resolutions obtained were 75nm and 16nm, respectively. The reliability of this last result is discussed in terms of the survey of the last large-angle deflection undergone by the backscattered electrons involved in the diffraction process. Bearing in mind the mean transversal resolution found, it was possible to detect small area grains of sigma phase by EBSD measurements, for a stabilized austenitic AISI 347 stainless steel under heat treatments, simulating post welding (40h at 600°C) and aging (284h at 484°C) effects-as usually occurring in nuclear reactor pressure vessels.

  5. Gauged linear sigma model and pion-pion scattering

    SciTech Connect

    Fariborz, Amir H.; Schechter, Joseph; Shahid, M. Naeem

    2009-12-01

    A simple gauged linear sigma model with several parameters to take the symmetry breaking and the mass differences between the vector meson and the axial vector meson into account is considered here as a possibly useful 'template' for the role of a light scalar in QCD as well as for (at a different scale) an effective Higgs sector for some recently proposed walking technicolor models. An analytic procedure is first developed for relating the Lagrangian parameters to four well established (in the QCD application) experimental inputs. One simple equation distinguishes three different cases: i. QCD with axial vector particle heavier than vector particle, ii. possible technicolor model with vector particle heavier than the axial vector one, iii. the unphysical QCD case where both the Kawarabayashi-Suzuki-Riazuddin-Fayazuddin and Weinberg relations hold. The model is applied to the s-wave pion-pion scattering in QCD. Both the near threshold region and (with an assumed unitarization) the 'global' region up to about 800 MeV are considered. It is noted that there is a little tension between the choice of 'bare' sigma mass parameter for describing these two regions. If a reasonable 'global' fit is made, there is some loss of precision in the near threshold region.

  6. A high-sigma model of pulsar wind nebulae

    NASA Astrophysics Data System (ADS)

    Lyutikov, Maxim

    2010-07-01

    Pulsars and central engines of long gamma-ray bursts - collapsars - may produce highly magnetized (Poynting-flux-dominated) outflows expanding in dense surroundings (interstellar medium or stellar material). For certain injection conditions, the magnetic flux of the wind cannot be accommodated within the cavity. In this case, ideal (non-dissipative) magnetohydrodynamics models, similar to the Kennel & Coroniti model of the Crab nebula, break down (the so-called `sigma problem'). This is typically taken to imply that the wind should become particle-dominated on scales much smaller than the size of the cavity. The wind is then slowed down by a fluid-type (low magnetization) reverse shock. Recent Fermi results, indicating that the synchrotron spectrum of the Crab nebula extends well beyond the upper limit of the most efficient radiation-reaction-limited acceleration, contradict the presence of a low-sigma reverse shock. We propose an alternative possibility, that in nearly aligned pulsars the excessive magnetic flux is destroyed in a reconnection-like process in two regions: near the rotational axis and near the equator. We construct an example of such a highly magnetized wind having two distinct reconnection regions and suggest that these reconnection sites are observed as tori and jets in pulsar wind nebulae. The model reproduces, qualitatively, the observed morphology of the Crab nebula. In parts of the nebula dissipation occurs in a relativistically moving wind, alleviating requirements on the acceleration rate.

  7. 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).

  8. 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.

  9. Franck-Condon factors for photodetachment from LiO(-), NaO(-), and KO(-)

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Partridge, Harry; Pettersson, Lars G. M.

    1993-01-01

    The 1Sigma(+), 3Sigma(+), 1Pi, and 3Pi states of the negative ions and the 2Pi and 2Sigma(+) states of the neutral alkali oxides are studied at high levels of theory. The calculations show that ground state of the negative ions changes from 3Pi for LiO(-) to 1Sigma(+) for KO(-). Although the calculations give a 3Pi ground state for NaO(-), we cannot rule out the possibility that the very low-lying 1Sigma(+) state is the true ground state. The Franck-Condon factors for photodetachment of an electron from the 1Sigma(+) and/or 3Pi states of the negative ion are presented to help interpret photodetachment experiments. Our best results for the A 2Sigma(+) - X 2Pi separations in LiO and NaO are 2496 and 2061/cm, which are in excellent agreement with that deduced (2516 and 2018/cm) from experiment.

  10. Purification and characterization of the guinea pig sigma-1 receptor functionally expressed in Escherichia coli.

    PubMed

    Ramachandran, Subramaniam; Lu, Hongliang; Prabhu, Usha; Ruoho, Arnold E

    2007-02-01

    Sigma receptors once considered as a class of opioid receptors are now regarded as unique orphan receptors, distinguished by the ability to bind various pharmacological agents such as the progesterone (steroid), haloperidol (anti-psychotic), and drugs of abuse such as cocaine and methamphetamine. The sigma-1 receptor is a 223 amino acid protein, proposed to have two transmembrane segments. We have developed a scheme for the purification of the guinea pig sigma-1 receptor following overexpression in Escherichia coli as a maltose binding protein (MBP) fusion and extraction with Triton X-100. Affinity chromatography using an amylose column and Ni2+ affinity column was used to purify the sigma-1 receptor. The sigma-1 receptor purified by this method is a 26 kDa polypeptide as assessed by SDS-PAGE, binds sigma ligands with high affinity and can be specifically photoaffinity labeled with the sigma-1 receptor photoprobe, [125I]-iodoazidococaine. Ligand binding using [3H]-(+)-pentazocine indicated that approximately half of the purified protein in Triton X-100 bound to radioligand. The MBP-sigma-1 receptor and the sigma-1 receptor in 0.5% triton were maximally stable for approximately two weeks at -20 degrees C in buffer containing 30% glycerol.

  11. Aβ mediates Sigma receptor degradation via CaN/NFAT pathway

    PubMed Central

    Fang, Min; Zhang, Pei; Zhao, Yanxin; Jin, Aiping; Liu, Xueyuan

    2016-01-01

    Sigma receptor is an endoplasmic reticulum protein and belongs to non-opioid receptor. Increasing evidence shows that Sigma receptor activation can significantly attenuate AD induced neurological dysfunction and the functional deficiency of Sigma receptor plays an important role in the Aβ induced neuronal loss. This study aimed to investigate the influence of extracellular accumulation of Aβ on the Sigma receptor expression. Our results showed the increase in extracellular Aβ had little influence on the mRNA expression of Sigma receptor, but gradually reduced its protein expression. Co-immunoprecipitation was employed to evaluate the interaction of Sigma receptor with other proteins. Results showed BIP could bind to Sigma receptor to affect the ubiquitination of Sigma receptor. Further investigation showed there was a NFAT binding site at the promoter of BIP. Then, Western blot assay was performed to detect NFAT expression. Results showed extracellular Aβ affected the nuclear translocation of NFAT and the CaN activity of NFAT also increased with the accumulation of extracellular Aβ. In this study, NFAT-BIP luciferase reporter gene system was constructed. Results showed NFAT was able to regulate the transcription of BIP. Thus, we speculate that extracellular Aβ accumulation may activate CaN/NFAT signaling pathway to induce chaperone BIP expression, which results in Sigma receptor ubiquitination and its degradation. PMID:27648137

  12. sigma, a repetitive element found adjacent to tRNA genes of yeast.

    PubMed Central

    del Rey, F J; Donahue, T F; Fink, G R

    1982-01-01

    sigma is a DNA element of about 340 base pairs (bp) that is repeated many times in the yeast genome. The element has 8-bp inverted repeats at its ends and is flanked by 5-bp direct repeats. The 5-bp repeats are different for each sigma and have no homology with the ends of the sigma sequence. sigma is located 16 or 18 bp from the 5' end of several tRNA genes. Southern analysis of different yeast strains shows that the pattern of hybridization is different even for closely related strains. Images PMID:6287468

  13. Quality assurance and management in microelectronics companies: ISO 9000 versus Six Sigma

    NASA Astrophysics Data System (ADS)

    Lupan, Razvan; Kobi, Abdessamad; Robledo, Christian; Bacivarov, Ioan; Bacivarov, Angelica

    2009-01-01

    A strategy for the implementation of the Six Sigma method as an improvement solution for the ISO 9000:2000 Quality Standard is proposed. Our approach is focused on integrating the DMAIC cycle of the Six Sigma method with the PDCA process approach, highly recommended by the standard ISO 9000:2000. The Six Sigma steps applied to each part of the PDCA cycle are presented in detail, giving some tools and training examples. Based on this analysis the authors conclude that applying Six Sigma philosophy to the Quality Standard implementation process is the best way to achieve the optimal results in quality progress and therefore in customers satisfaction.

  14. Six Sigma Quality Management System and Design of Risk-based Statistical Quality Control.

    PubMed

    Westgard, James O; Westgard, Sten A

    2017-03-01

    Six sigma concepts provide a quality management system (QMS) with many useful tools for managing quality in medical laboratories. This Six Sigma QMS is driven by the quality required for the intended use of a test. The most useful form for this quality requirement is the allowable total error. Calculation of a sigma-metric provides the best predictor of risk for an analytical examination process, as well as a design parameter for selecting the statistical quality control (SQC) procedure necessary to detect medically important errors. Simple point estimates of sigma at medical decision concentrations are sufficient for laboratory applications.

  15. The structure of alkali metal derivatives of azoles: N-sigma versus pi structures.

    PubMed

    Blanco, Fernando; Alkorta, Ibon; Elguero, Jose

    2008-08-21

    High level ab initio calculations have been used to study the relative stability of N-sigma and pi configurations of the neutral alkaline derivatives of azoles. The N-sigma structure is the one normally expected for nonionized azolate salts. However, the results show that in the case of the pyrrole and imidazole the pi configuration is more stable than the N-sigma one. The preference of the N-sigma vs pi configurations is related to the presence or the absence of two contiguous nitrogen atoms in the azole ring. A search in the CSD shows that some pyrrolate and imidazolate salts exist in solid phase in the pi configuration.

  16. 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.

  17. Baculovirus surface display of sigmaC and sigmaB proteins of avian reovirus and immunogenicity of the displayed proteins in a mouse model.

    PubMed

    Lin, Yueh H; Lee, Long H; Shih, Wen L; Hu, Yu C; Liu, Hung J

    2008-11-25

    Avian reovirus (ARV), an important pathogen in poultry, causes arthritis, chronic respiratory disease, and malabsorption syndrome that cause considerable economic losses to the poultry industry. In present study, we have succeeded in construction of a universal baculovirus surface display system (UBSDS) that can display different foreign proteins on the envelope of baculovirus. Sequences encoding the signal peptide (SS), transmembrane domain (TM), and cytoplasmic domain (CTD) derived from the gp64 protein of baculovirus and histidine tag, respectively were inserted into the pBacCE vector. Four restriction enzyme sites between the histidine tag and gp64 transmembrane domain were established for expression of different foreign proteins. The transmembrane domain and CTD of gp64 in the platform were designed in order to improve stability and quantity of foreign proteins on the envelope of baculovirus. The sigmaC and sigmaB proteins of ARV are known to elicit neutralizing antibodies against ARV. The UBSDS was therefore used to express sigmaC and sigmaB proteins on the envelope of baculovirus. Two recombinant baculoviruses BacSC-sigmaC and BacSC-sigmaB have been successfully constructed. After infection, both His6-tagged recombinant sigmaC (rsigmaC) and sigmaB (rsigmaB) proteins were displayed on the envelope of recombinant baculoviruses and the recombinant viral proteins were anchored on the plasma membrane of Sf-9 cells, as revealed by immunofluorescence staining (IFS) and confocal microscopy. The antigenicity of rsigmaC and rsigmaB proteins was demonstrated by Western blotting assay. Immunogold electron microscopy demonstrated that both recombinant viruses displayed rsigmaC and rsigmaB proteins on the viral surface. Immunization of BALB/c mice with recombinant viruses, demonstrated that serum from the BacSC-sigmaC and BacSC-sigmaB treated models had significant higher levels of virus neutralization activities than the control groups. This demonstrates that the

  18. Application of sigma metrics for the assessment of quality assurance in clinical biochemistry laboratory in India: a pilot study.

    PubMed

    Singh, Bhawna; Goswami, Binita; Gupta, Vinod Kumar; Chawla, Ranjna; Mallika, Venkatesan

    2011-04-01

    Ensuring quality of laboratory services is the need of the hour in the field of health care. Keeping in mind the revolution ushered by six sigma concept in corporate world, health care sector may reap the benefits of the same. Six sigma provides a general methodology to describe performance on sigma scale. We aimed to gauge our laboratory performance by sigma metrics. Internal quality control (QC) data was analyzed retrospectively over a period of 6 months from July 2009 to December 2009. Laboratory mean, standard deviation and coefficient of variation were calculated for all the parameters. Sigma was calculated for both the levels of internal QC. Satisfactory sigma values (>6) were elicited for creatinine, triglycerides, SGOT, CPK-Total and Amylase. Blood urea performed poorly on the sigma scale with sigma <3. The findings of our exercise emphasize the need for detailed evaluation and adoption of ameliorative measures in order to effectuate six sigma standards for all the analytical processes.

  19. 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.

  20. 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.

  1. 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.

  2. Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury.

    PubMed

    de la Puente, Beatriz; Nadal, Xavier; Portillo-Salido, Enrique; Sánchez-Arroyos, Ricard; Ovalle, Sergio; Palacios, Gabriel; Muro, Asunción; Romero, Luz; Entrena, José Manuel; Baeyens, José Manuel; López-García, José Antonio; Maldonado, Rafael; Zamanillo, Daniel; Vela, José Miguel

    2009-10-01

    Sigma-1 receptor (sigma(1)R) is expressed in key CNS areas involved in nociceptive processing but only limited information is available about its functional role. In the present study we investigated the relevance of sigma(1)R in modulating nerve injury-evoked pain. For this purpose, wild-type mice and mice lacking the sigma(1)R gene were exposed to partial sciatic nerve ligation and neuropathic pain-related behaviors were investigated. To explore underlying mechanisms, spinal processing of repetitive nociceptive stimulation and expression of extracellular signal-regulated kinase (ERK) were also investigated. Sensitivity to noxious heat of homozygous sigma(1)R knockout mice did not differ from wild-type mice. Baseline values obtained in sigma(1)R knockout mice before nerve injury in the plantar, cold-plate and von Frey tests were also indistinguishable from those obtained in wild-type mice. However, cold and mechanical allodynia did not develop in sigma(1)R null mice exposed to partial sciatic nerve injury. Using isolated spinal cords we found that mice lacking sigma(1)R showed reduced wind-up responses respect to wild-type mice, as evidenced by a reduced number of action potentials induced by trains of C-fiber intensity stimuli. In addition, in contrast to wild-type mice, sigma(1)R knockout mice did not show increased phosphorylation of ERK in the spinal cord after sciatic nerve injury. Both wind-up and ERK activation have been related to mechanisms of spinal cord sensitization. Our findings identify sigma(1)R as a constituent of the mechanisms modulating activity-induced sensitization in pain pathways and point to sigma(1)R as a new potential target for drugs designed to alleviate neuropathic pain.

  3. Characterization of Bax-sigma, a cell death-inducing isoform of Bax.

    PubMed

    Schmitt, E; Paquet, C; Beauchemin, M; Dever-Bertrand, J; Bertrand, R

    2000-04-21

    The Ced-9/Bcl-like family of genes codes for proteins that have antiapoptotic and proapoptotic activity. Several Bax isoproteins have been detected by 2-D gel electrophoresis, and a novel human member, designated as Bax-sigma, has been identified and cloned from human cancer promyelocytic cells. Bax-sigma contains BH-3, BH-1, and BH-2 domains, putative alpha-5 and alpha-6 helices, and the carboxy-terminal hydrophobic transmembrane domain but lacks amino acids 159 to 171 compared to Bax-alpha. mRNA expression analysis by reverse transcription-polymerase chain reaction and RNase protection assays have revealed that Bax-sigma is expressed in a variety of human cancer cell lines and normal tissues. To investigate the potential role of Bax-sigma in apoptosis, first its effects were compared to those of Bax-alpha by transient expression in human B lymphoma Namalwa cells. Both Bax-sigma and Bax-alpha promoted apoptosis, as detected by DNA fragmentation and morphological analysis by electron microscopy. The apoptosis induced by Bax-sigma and Bax-alpha was correlated with their expression, cytochrome c release, and caspase activation. In a yeast two-hybrid system, Bax-sigma interacted with several Ced-9/Bcl family members but had no affinity for the human Egl-1 homologs Bik and Bad and the Ced-4 homolog Apaf-1. In human cells, Bax-sigma function was counteracted by Bcl-xL overexpression, and co-immunoprecipitation experiments indicated that Bax-sigma was associated with Bcl-xL. Furthermore, Bax-sigma overexpression increased cell death induced by various concentrations of genotoxic agents with the most pronounced effect occurring at low camptothecin and vinblastine dose levels. Our results suggest that Bax-sigma, a novel variant of Bax, encodes a protein with a proapoptotic effect and mode of action similar to those of Bax-alpha.

  4. Sigma-1 receptors modulate neonatal Nav1.5 ion channels in breast cancer cell lines.

    PubMed

    Aydar, Ebru; Stratton, Dan; Fraser, Scott P; Djamgoz, Mustafa B A; Palmer, Christopher

    2016-10-01

    The main aim of this study was to investigate a possible functional connection between sigma-1 receptors and voltage-gated sodium channels (VGSCs) in human breast cancer cells. The hypothesis was that sigma-1 drugs could alter the metastatic properties of breast cancer cells via the VGSC. Evidence was found for expression of sigma-1 receptor and neonatal Nav1.5 (nNav1.5) expression in both MDA-MB-231 and MDA-MB-468 cells. Sigma-1 drugs (SKF10047 and dimethyltryptamine) did not affect cell proliferation or migration but significantly reduced adhesion to the substrate. Silencing sigma-1 receptor expression by siRNA similarly reduced the adhesion. Blocking nNav1.5 activity with a polyclonal antibody (NESOpAb) targeting an extracellular region of nNav1.5 also reduced the adhesion in both cell lines. Importantly, the results of combined treatments with NESOpAb and a sigma-1 drug or sigma-1 siRNA suggested that both treatments targeted the same mechanism. The possibility was tested, therefore, that the sigma-1 receptor and the nNav1.5 channel formed a physical, functional complex. This suggestion was supported by the results of co-immunoprecipitation experiments. Furthermore, application of sigma-1 drugs to the cells reduced the surface expression of nNav1.5 protein, which could explain how sigma-1 receptor activation could alter the metastatic behaviour of breast cancer cells. Overall, these results are consistent with the idea of a sigma-1 protein behaving like either a "chaperone" or a regulatory subunit associated with nNav1.5.

  5. A comparison of methods for computing the sigma-coordinate pressure gradient force for flow over sloped terrain in a hybrid theta-sigma model

    NASA Technical Reports Server (NTRS)

    Johnson, D. R.; Uccellini, L. W.

    1983-01-01

    In connection with the employment of the sigma coordinates introduced by Phillips (1957), problems can arise regarding an accurate finite-difference computation of the pressure gradient force. Over steeply sloped terrain, the calculation of the sigma-coordinate pressure gradient force involves computing the difference between two large terms of opposite sign which results in large truncation error. To reduce the truncation error, several finite-difference methods have been designed and implemented. The present investigation has the objective to provide another method of computing the sigma-coordinate pressure gradient force. Phillips' method is applied for the elimination of a hydrostatic component to a flux formulation. The new technique is compared with four other methods for computing the pressure gradient force. The work is motivated by the desire to use an isentropic and sigma-coordinate hybrid model for experiments designed to study flow near mountainous terrain.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Vacuum Stability in Kaluza-Klein Geometric Sigma Models

    NASA Astrophysics Data System (ADS)

    Vasilić, M.

    2002-09-01

    In Kaluza-Klein geometric sigma models, the scalar fields coupled to higher-dimensional gravity are pure gauge. The gauge fixed theory contains no matter fields, and can consistently be reduced to 4 dimensions, provided the internal space is chosen in the form of a group manifold. The effective 4-dimensional theory includes standard Einstein and Yang-Mills sectors, and is free of the classical cosmological constant problem. In this paper, the stability of the internal excitations is analyzed. It is shown that the initial Lagrangian can be modified to lead to a classically stable effective 4-dimensional theory, independently of the particular group used, and retaining all the basic features of the unmodified theory.

  11. 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%.

  12. 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.

  13. 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.

  14. Perturbative and nonperturbative aspects of heterotic sigma models

    NASA Astrophysics Data System (ADS)

    Cui, Xiaoyi

    Supersymmetric nonlinear sigma models are interesting from various perspectives. They are useful for understanding the most fundamental theory of our world, and for low-energy effective model-building. Mathematically, they make surprising connections between different exciting areas such as complex geometry, deformation theory, quantum algebra and topology. In this thesis, we study perturbative and nonperturbative aspects of sigma models with N = (0, 2) supersymmetry, with an emphasize on a possible version of extended 4d/2d correspondence. We showed that in some N = (0, 2) models, β functions calculated through Feynman graphs can be reproduced by nonrenormalization theorems. And the result can further be compared with the supercurrent analysis. These cases including linear models, minimal CP(1) model (other CP(N) models are obstructed by global anomaly) together with its extended cousins, and heterotic CP(N) models. Nonperturbatively we built the instanton measure for minimal CP(1) model and its (0, 2)-extended cousins. The instanton measure bears similarity to the instanton measure for 4d super-Yang-Mills theories. Through this analogy, there seems to be a correspondence between N = 1 theories in 4d and N = (0, 2) theories in 2d, which extends previous results initiated by Edalati-Tong and Shifman-Yung. An interesting by-product is also obtained during the procedure, which shows that for non-minimal (globally anomaly-free) N = (0, 2) models with CP(1) as target spaces, there seems always exist certain infrared fixed points, induced by the behavior of chiral fermions.

  15. 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

  16. 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…

  17. 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…

  18. Sigma-1 receptors bind cholesterol and remodel lipid rafts in breast cancer cell lines.

    PubMed

    Palmer, Christopher P; Mahen, Robert; Schnell, Eva; Djamgoz, Mustafa B A; Aydar, Ebru

    2007-12-01

    Lipid rafts are membrane platforms that spatially organize molecules for specific signaling pathways that regulate various cellular functions. Cholesterol is critical for liquid-ordered raft formation by serving as a spacer between the hydrocarbon chains of sphingolipids, and alterations in the cholesterol contents of the plasma membrane causes disruption of rafts. The role that sigma receptors play in cancer is not clear, although it is frequently up-regulated in human cancer cells and tissues and sigma receptors inhibit proliferation in carcinoma and melanoma cell lines, induce apoptosis in colon and mammary carcinoma cell lines, and reduce cellular adhesion in mammary carcinoma cell lines. In this study, we provide molecular and functional evidence for the involvement of the enigmatic sigma 1 receptors in lipid raft modeling by sigma 1 receptor-mediated cholesterol alteration of lipid rafts in breast cancer cell lines. Cholesterol binds to cholesterol recognition domains in the COOH terminus of the sigma 1 receptor. This binding is blocked by sigma receptor drugs because the cholesterol-binding domains form part of the sigma receptor drug-binding site, mutations of which abolish cholesterol binding. Furthermore, we outline a hypothetical functional model to explain the myriad of biological processes, including cancer, in which these mysterious receptors are involved. The findings of this study provide a biological basis for the potential therapeutic applications of lipid raft cholesterol regulation in cancer therapy using sigma receptor drugs.

  19. 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.

  20. 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…

  1. 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…

  2. sigmaB-dependent protein induction in Listeria monocytogenes during vancomycin stress.

    PubMed

    Shin, Ji-Hyun; Kim, Jungmin; Kim, Sung-Min; Kim, Shukho; Lee, Je-Chul; Ahn, Jung-Mo; Cho, Je-Yoel

    2010-07-01

    Listeria monocytogenes is a food-borne pathogen that can survive under a wide range of environmental and energy stress conditions. The general stress response controlled by sigma(B) largely contributes to stress resistance in L. monocytogenes. Moreover, the bacterial cell wall is the first defense against cellular stress and as such is the target of numerous antibiotics. We therefore hypothesize that sigma(B) contributes to monitoring the integrity of cell walls. We evaluated sigma(B) activity in wild type and DeltasigB mutant L. monocytogenes containing reporter fusions (sigma(B)-dependent opuCA promoter and a lacZ reporter gene) during the early exponential growth phase by measuring the specific activity of beta-galactosidase after vancomycin (2 microg mL(-1) final concentration) stress. sigma(B) activity is significantly induced only in the wild-type strain by addition of vancomycin. In addition, we identified sigma(B)-dependent vancomycin-inducible proteins using LC-ESI-MS/MS analysis. Two independent proteomic analyses confirmed the minimum twofold upregulation of 18 vancomycin-inducible sigma(B)-dependent stress response proteins in the wild-type strain compared with the DeltasigB mutant. The functions of these proteins are associated with cell wall biogenesis, intracellular transport, general stress response, cell metabolism and virulence. These results suggest that the sigma(B) protein may contribute to the monitoring of cell wall integrity.

  3. 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…

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. The sigma-2 receptor as a therapeutic target for drug delivery in triple negative breast cancer

    PubMed Central

    Makvandi, Mehran; Tilahun, Estifanos D.; Lieberman, Brian P.; Anderson, Redmond-Craig; Zeng, Chenbo; Xu, Kuiying; Hou, Catherine; McDonald, Elizabeth S.; Pryma, Daniel A.; Mach, Robert H.

    2015-01-01

    Background Triple-negative breast cancer (TNBC) is associated with high relapse rates and increased mortality when compared with other breast cancer subtypes. In contrast to receptor positive breast cancers, there are no approved targeted therapies for TNBC. Identifying biomarkers for TNBC is of high importance for the advancement of patient care. The sigma-2 receptor has been shown to be overexpressed in triple negative breast cancer in vivo and has been characterized as a marker of proliferation. The aim of the present study was to define the sigma-2 receptor as a target for therapeutic drug delivery and biomarker in TNBC. Methods Three TNBC cell lines were evaluated: MDA-MB-231, HCC1937 and HCC1806. Sigma-2 compounds were tested for pharmacological properties specific to the sigma-2 receptor through competitive inhibition assays. Sigma-2 receptor expression was measured through radioligand receptor saturation studies. Drug sensitivity for taxol was compared to a sigma-2 targeting compound conjugated to a cytotoxic payload, SW IV-134. Cell viability was assessed after treatments for 2 or 48 hours. Sigma-2 blockade was assessed to define sigma-2 mediated cytotoxicity of SW IV-134. Caspase 3/7 activation induced by SW IV-134 was measured at corresponding treatment time points. Results: SW IV-134 was the most potent compound tested in two of the three cell lines and was similarly effective in all three. MDA-MB-231 displayed a statistically significant higher sigma-2 receptor expression and also was the most sensitive cell line evaluated to SW IV-134. Conclusion Targeting the sigma-2 receptor with a cytotoxic payload was effective in all the three cell lines evaluated and provides the proof of concept for future development of a therapeutic platform for the treatment of TNBC. PMID:26453012

  9. Sigma1 Targeting to Suppress Aberrant Androgen Receptor Signaling in Prostate Cancer.

    PubMed

    Thomas, Jeffrey D; Longen, Charles G; Oyer, Halley M; Chen, Nan; Maher, Christina M; Salvino, Joseph M; Kania, Blase; Anderson, Kelsey N; Ostrander, William F; Knudsen, Karen E; Kim, Felix J

    2017-02-24

    Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1 mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that treatment with a small molecule Sigma1 inhibitor prevented 5α- dihydrotestosterone (DHT)-mediated nuclear translocation of AR and induced proteasomal degradation of AR and ARV, suppressing the transcriptional activity and protein levels of both full-length and splice-variant AR. Consistent with these data, RNAi knockdown of Sigma1 resulted in decreased AR levels and transcriptional activity. Furthermore, Sigma1 physically associated with ARV7 and ARv567es as well as full-length AR. Treatment of mice xenografted with ARV-driven CPRC tumors with a drug-like small molecule Sigma1 inhibitor significantly inhibited tumor growth associated with elimination of AR and ARV7 in responsive tumors. Together, our data show that Sigma1 modulators can be used to suppress AR/ARV-driven prostate cancer cells via regulation of pharmacologically responsive Sigma1-AR/ARV interactions both in vitro and in vivo.

  10. 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.

  11. Electrophilicity of aromatic triflones in sigma-complexation processes.

    PubMed

    El Guesmi, Nizar; Boubaker, Taoufik; Goumont, Régis; Terrier, François

    2008-11-07

    The kinetics of sigma-complexation of 2,6-bis(trifluoromethanesulfonyl)-4-nitroanisole (4) have been investigated over a large pH range of 2-15.68 in methanol. Two competitive processes have been identified with the initial addition of MeO(-) at the unsubstituted 3-position of 4 to give a 1,3-dimethoxy adduct (4b-Me) and a subsequent and slow conversion of this species into the 1,1-dimethoxy isomer (4a-Me). Both 4a-Me and 4b-Me are more stable than the related adducts of 2,6-dinitro-4-trifluromethanesulfonylanisole, i.e.5a-Me and 5b-Me, and 2,4,6-trinitroanisole, i.e.6a-Me and 6b-Me, the latter compound being a conventional reference aromatic electrophile in Meisenheimer complex chemistry. The high thermodynamic stability of 4a-Me (pK(a) = 10.48) and 4b-Me (pK(a) = 12.23) relative to 5a-Me (pK(a) = 10.68) and 6a-Me (pK(a) = 12.56) or 5b-Me (pK(a) = 15.38) and 6b-Me (pK(a) = 16.46), is shown to derive from an especially high capacity of a para or an ortho SO(2)CF(3) group to stabilize a negative charge through Fpi-type polarization effects. From the kinetic data, it appears that the contribution of a methanol pathway to the formation of 4a-Me is much weaker than that found to operate in the formation of the 1,1-complex 5a-Me of 2,6-dinitro-4-trifluromethanesulfonylanisole, the experimental evidence suggesting that the reactivity of 4 and 5 is located just beyond the region defining the boundary between super- and normal-electrophilicity in methanol. Comparison of our results with available literature data show that this boundary corresponds to a pK(MeOH)(a) value of approximately 10, in agreement with our previous finding of a very effective solvent contribution to the sigma-complexation of 1,3,5-tris(trifluoromethanesulfonyl)benzene (13; pK(MeOH)(a) = 9.12) in methanol. Taking advantage of our observation that pK(MeOH)(a) and pK(H(2)O)(a) values for sigma-complexation at unsubstituted ring positions are related by a nice linear correlation, an approximate ranking

  12. 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

  13. 77 FR 67675 - Importer of Controlled Substances, Notice of Registration, SA INTL GMBH C/O., Sigma Aldrich Co...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-13

    ... Enforcement Administration Importer of Controlled Substances, Notice of Registration, SA INTL GMBH C/O., Sigma..., 2012, 77 FR 50162, SA INTL GMBH C/O., Sigma Aldrich Co., LLC., 3500 Dekalb Street, St. Louis, Missouri... C/O., Sigma Aldrich Co. LLC., to import the basic classes of controlled substances is...

  14. 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.

  15. Sigma: Strain-level inference of genomes from metagenomic analysis for biosurveillance

    PubMed Central

    Ahn, Tae-Hyuk; Chai, Juanjuan; Pan, Chongle

    2015-01-01

    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. 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. Contact: panc@ornl.gov Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25266224

  16. Sigma: Strain-level inference of genomes from metagenomic analysis for biosurveillance

    DOE PAGES

    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

  17. 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

  18. Dual pairs of gauged linear sigma models and derived equivalences of Calabi-Yau threefolds

    NASA Astrophysics Data System (ADS)

    Gerhardus, Andreas; Jockers, Hans

    2017-04-01

    In this work we study the phase structure of skew symplectic sigma models, which are a certain class of two-dimensional N =(2 , 2) non-Abelian gauged linear sigma models. At low energies some of them flow to non-linear sigma models with Calabi-Yau target spaces, which emerge from non-Abelian strong coupling dynamics. The observed phase structure results in a non-trivial duality proposal among skew symplectic sigma models and connects non-complete intersection Calabi-Yau threefolds-that are non-birational among another-in a common quantum Kähler moduli space. As a consequence we find non-trivial identifications of spectra of topological B-branes, which from a modern algebraic geometry perspective imply derived equivalences among Calabi-Yau varieties. To further support our proposals, we calculate the two sphere partition function of skew symplectic sigma models to determine geometric invariants, which confirm the anticipated Calabi-Yau threefold phases. We show that the two sphere partition functions of a pair of dual skew symplectic sigma models agree in a non-trivial fashion. To carry out these calculations, we develop a systematic approach to study higher-dimensional Mellin-Barnes type integrals. In particular, these techniques admit the evaluation of two sphere partition functions for gauged linear sigma models with higher rank gauge groups, but are applicable in other contexts as well.

  19. Synthesis and evaluation of tetrahydroindazole derivatives as sigma-2 receptor ligands.

    PubMed

    Wu, Zong-Wen; Song, Shu-Yong; Li, Li; Lu, He-Lin; Lieberman, Brian; Huang, Yun-Sheng; Mach, Robert H

    2015-04-01

    A series of tetrahydroindazole derivatives were synthesized and evaluated for their affinities for both sigma-1 and sigma-2 receptors. These compounds are hybrid structures of a tetrahydroindazole substituted benzamide and a 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline moiety or a 9-azabicyclo[3.3.1]nonan-3-yl-amine moiety. These newly synthesized hybrid analogs showed various affinities for sigma-2 receptor without any significant affinities for sigma-1 receptor. In particular, compounds 12, 15b, 15c, and 15d, demonstrated moderate affinity and excellent selectivity for sigma-2 receptor. It is interesting to note that 3-5 carbon units between the tetrahydroindazole substituted benzamide and the 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline moiety are appropriate for sigma-2 receptor binding. No substitution on the 9-aza nitrogen is proper for sigma-2 affinity in the 2-(9-azabicyclo[3.3.1]nonan-3-yl-amino)-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)benzamide analogs.

  20. 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 +}.

  1. 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

  2. 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

  3. Identifying sigma70 promoters with novel pseudo nucleotide composition.

    PubMed

    Lin, Hao; Liang, Zhi-Yong; Tang, Hua; Chen, Wei

    2017-02-08

    Promoters are DNA regulatory elements located directly upstream or at the 5' end of the transcription initiation site (TSS), which are in charge of gene transcription initiation. With the completion of a large number of microorganism genomics, it is urgent to predict promoters accurately in bacteria by using computational method. In this work, a sequence-based predictor named "iPro70-PseZNC" was designed for identifying sigma70 promoters in prokaryote. In the predictor, the samples of DNA sequences are formulated by a novel pseudo nucleotide composition, called PseZNC, into which the multi-window Z-curve composition and six local DNA structural properties are incorporated. In the 5-fold cross-validation, the area under the curve of receiver operating characteristic of 0.909 was obtained on our benchmark dataset, indicating that the proposed predictor is promising and will provide important guide in this area. Further studies showed that the performance of PseZNC is better than it of multi-window Z-curve composition. For the sake of convenience for researchers, a user-friendly online service was established and can be freely accessible at http://lin.uestc.edu.cn/server/iPro70-PseZNC. The PseZNC approach can be also extended to other DNA-related problems.

  4. Regulating ankyrin dynamics: Roles of sigma-1 receptors.

    PubMed

    Hayashi, T; Su, T P

    2001-01-16

    Ankyrin is a cytoskeletal adaptor protein that controls important cellular functions, including Ca(2+) efflux at inositol 1,4,5-trisphosphate receptors (IP(3)R) on the endoplasmic reticulum. The present study found that sigma-1 receptors (Sig-1R), unique endoplasmic reticulum proteins that bind certain steroids, neuroleptics, and psychotropic drugs, form a trimeric complex with ankyrin B and IP(3)R type 3 (IP(3)R-3) in NG-108 cells. The trimeric complex could be coimmunoprecipitated by antibodies against any of the three proteins. Sig-1R agonists such as pregnenolone sulfate and cocaine caused the dissociation of an ankyrin B isoform (ANK 220) from IP(3)R-3. This effect caused by Sig-1R agonists was blocked by a Sig-1R antagonist. The degree of dissociation of ANK 220 from IP(3)R-3 caused by Sig-1R ligands correlates excellently with the ligands' efficacies in potentiating the bradykinin-induced increase in cytosolic free Ca(2+) concentration. Immunocytohistochemistry showed that Sig-1R, ankyrin B, and IP(3)R-3 are colocalized in NG-108 cells in perinuclear areas and in regions of cell-to-cell communication. These results suggest that Sig-1R and associated ligands may play important roles in cells by controlling the function of cytoskeletal proteins and that the Sig-1R/ANK220/IP(3)R-3 complex regulating Ca(2+) signaling may represent a site of action for neurosteroids and cocaine.

  5. 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 %.

  6. 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.

  7. Optimal experimental design with the sigma point method.

    PubMed

    Schenkendorf, R; Kremling, A; Mangold, M

    2009-01-01

    Using mathematical models for a quantitative description of dynamical systems requires the identification of uncertain parameters by minimising the difference between simulation and measurement. Owing to the measurement noise also, the estimated parameters possess an uncertainty expressed by their variances. To obtain highly predictive models, very precise parameters are needed. The optimal experimental design (OED) as a numerical optimisation method is used to reduce the parameter uncertainty by minimising the parameter variances iteratively. A frequently applied method to define a cost function for OED is based on the inverse of the Fisher information matrix. The application of this traditional method has at least two shortcomings for models that are nonlinear in their parameters: (i) it gives only a lower bound of the parameter variances and (ii) the bias of the estimator is neglected. Here, the authors show that by applying the sigma point (SP) method a better approximation of characteristic values of the parameter statistics can be obtained, which has a direct benefit on OED. An additional advantage of the SP method is that it can also be used to investigate the influence of the parameter uncertainties on the simulation results. The SP method is demonstrated for the example of a widely used biological model.