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Sample records for oligopeptide transporter suppress

  1. Characterization of the PT clade of oligopeptide transporters in rice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oligopeptide transporters (OPTs) are a group of membrane-localized proteins with a broad range of substrate transport capabilities, and which are thought to contribute to many biological processes. Nine OPTs belonging to the peptide transport (PT) clade were identified in the rice (Oryza sativa L.) ...

  2. Electronic transport through oligopeptide chains: An artificial prototype of a molecular diode

    NASA Astrophysics Data System (ADS)

    Oliveira, J. I. N.; Albuquerque, E. L.; Fulco, U. L.; Mauriz, P. W.; Sarmento, R. G.

    2014-09-01

    Using an effective tight-binding model, together with a transfer matrix technique, we investigate the electronic transport through an oligopeptide chain composed by two amino acid pairs alanine-lysine (Ala-Lys) and threonine-alanine (Thr-Ala), respectively, sandwiched between two platinum electrodes. Our results show that factors such as the oligopeptide chain length and the possible combinations between the amino acids residues are crucial to the diode-like profile of the current-voltage (I-V) characteristics, whose asymmetric curves were analyzed using the inverted rectification ratio (IRR).

  3. H(+)/peptide transporter (PEPT2) is expressed in human epidermal keratinocytes and is involved in skin oligopeptide transport.

    PubMed

    Kudo, Michiko; Katayoshi, Takeshi; Kobayashi-Nakamura, Kumiko; Akagawa, Mitsugu; Tsuji-Naito, Kentaro

    2016-07-01

    Peptide transporter 2 (PEPT2) is a member of the proton-coupled oligopeptide transporter family, which mediates the cellular uptake of oligopeptides and peptide-like drugs. Although PEPT2 is expressed in many tissues, its expression in epidermal keratinocytes remains unclear. We investigated PEPT2 expression profile and functional activity in keratinocytes. We confirmed PEPT2 mRNA expression in three keratinocyte lines (normal human epidermal keratinocytes (NHEKs), immortalized keratinocytes, and malignant keratinocytes) by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR. In contrast to PEPT1, PEPT2 expression in the three keratinocytes was similar or higher than that in HepG2 cells, used as PEPT2-positive cells. Immunolocalization analysis using human skin showed epidermal PEPT2 localization. We studied keratinocyte transport function by measuring the oligopeptide content using liquid chromatography/tandem mass spectrometry. Glycylsarcosine uptake in NHEKs was pH-dependent, suggesting that keratinocytes could absorb small peptides in the presence of an inward H(+) gradient. We also performed a skin-permeability test of several oligopeptides using skin substitute, suggesting that di- and tripeptides pass actively through the epidermis. In conclusion, PEPT2 is expressed in keratinocytes and involved in skin oligopeptide uptake. PMID:27216463

  4. Peptide Selectivity of the Proton-Coupled Oligopeptide Transporter from Neisseria meningitidis.

    PubMed

    Sharma, Neha; Aduri, Nanda G; Iqbal, Anna; Prabhala, Bala K; Mirza, Osman

    2016-01-01

    Peptide transport in living organisms is facilitated by either primary transport, hydrolysis of ATP, or secondary transport, cotransport of protons. In this study, we focused on investigating the ligand specificity of the Neisseria meningitidis proton-coupled oligopeptide transporter (NmPOT). It has been shown that the gene encoding this transporter is upregulated during infection. NmPOT conformed to the typical chain length preference as observed in prototypical transporters of this family. In contrast to prototypical transporters, it was unable to accommodate a positively charged peptide residue at the C-terminus position of the substrate peptide. Sequence analysis of the active site of NmPOT displayed a distinctive aromatic patch, which has not been observed in any other transporters from this family. This aromatic patch may be involved in providing NmPOT with its atypical preferences. This study provides important novel information towards understanding how these transporters recognize their substrates. PMID:27438044

  5. Only One of Four Oligopeptide Transport Systems Mediates Nitrogen Nutrition in Staphylococcus aureus▿

    PubMed Central

    Hiron, Aurelia; Borezée-Durant, Elise; Piard, Jean-Christophe; Juillard, Vincent

    2007-01-01

    Oligopeptides internalized by oligopeptide permease (Opp) transporters play key roles in bacterial nutrition, signaling, and virulence. To date, two opp operons, opp-1 and opp-2, have been identified in Staphylococcus aureus. Systematic in silico analysis of 11 different S. aureus genomes revealed the existence of two new opp operons, opp-3 and opp-4, plus an opp-5A gene encoding a putative peptide-binding protein. With the exception of opp-4, the opp operons were present in all S. aureus strains. Within a single strain, the different opp operons displayed little sequence similarity and distinct genetic organization. Transcriptional studies showed that opp-1, opp-2, opp-3, and opp-4 operons were polycistronic and that opp-5A is monocistronic. We designed a minimal chemically defined medium for S. aureus RN6390 and showed that all opp genes were expressed but at different levels. Where tested, OppA protein production paralleled transcriptional profiles. opp-3, which encodes proteins most similar to known peptide transport proteins, displayed the highest expression level and was the only transporter to be regulated by specific amino acids, tyrosine and phenylalanine. Defined deletion mutants in one or several peptide permeases were constructed and tested for their capacity to grow in peptide-containing medium. Among the four putative Opp systems, Opp-3 was the only system able to provide oligopeptides for growth, ranging in length from 3 to 8 amino acids. Dipeptides were imported exclusively by DtpT, a proton-driven di- and tripeptide permease. These data provide a first complete inventory of the peptide transport systems opp and dtpT of S. aureus. Among them, the newly identified Opp-3 appears to be the main Opp system supplying the cell with peptides as nutritional sources. PMID:17496096

  6. Stability, metabolism and transport of D-Asp(OBzl)-Ala--a model prodrug with affinity for the oligopeptide transporter.

    PubMed

    Steffansen, B; Lepist, E I; Taub, M E; Larsen, B D; Frokjaer, S; Lennernäs, H

    1999-04-01

    The model prodrug D-Asp(OBzl)-Ala has previously been shown to have affinity and to be transported by the oligopeptide transporter PepT1 expressed in Caco-2 cells. The main objective of the present study was to investigate the aqueous stability of D-Asp(OBzl)-Ala and its in vitro metabolism in different gastrointestinal media arising from rats and humans, as well as in human plasma. The second major aim of the study was to evaluate our previous study in Caco-2 cell culture, by determining the effective intestinal permeability (Peff) of D-Asp(OBzl)-Ala in situ using the single-pass rat perfusion model. The aqueous stability studies show water, general buffer, as well as specific acid and base catalysis of D-Asp(OBzl)-Ala. The degradation of the model prodrug was independent of ionic strength. The half-lives in rat jejunal fluid and homogenate were >3 h. In human gastric and intestinal fluids, the half-lives were >3 h and 2.3+/-0. 03 h, respectively. Using the rat single-pass perfusion technique, the effective jejunal permeability (Peff) of D-Asp(OBzl)-Ala was determined to be high (1.29+/-0.5.10-4 cm/s). The 32 times higher Peff value found in the perfusion model compared to Caco-2 cells is most likely due to a higher functional expression of the oligopeptide transporter. Rat jejuna Peff was reduced by approximately 50% in the presence of well known oligopeptide transporter substrates, such as Gly-Sar and cephalexin. It may be that D-Asp(OBzl)-Ala is primarily absorbed intact by the rat jejunal oligopeptide transporter, since the stability in the intestinal homogenate and fluids was rather high (t1/2>2.3 h). PMID:10072480

  7. Accurate Prediction of Ligand Affinities for a Proton-Dependent Oligopeptide Transporter.

    PubMed

    Samsudin, Firdaus; Parker, Joanne L; Sansom, Mark S P; Newstead, Simon; Fowler, Philip W

    2016-02-18

    Membrane transporters are critical modulators of drug pharmacokinetics, efficacy, and safety. One example is the proton-dependent oligopeptide transporter PepT1, also known as SLC15A1, which is responsible for the uptake of the ?-lactam antibiotics and various peptide-based prodrugs. In this study, we modeled the binding of various peptides to a bacterial homolog, PepTSt, and evaluated a range of computational methods for predicting the free energy of binding. Our results show that a hybrid approach (endpoint methods to classify peptides into good and poor binders and a theoretically exact method for refinement) is able to accurately predict affinities, which we validated using proteoliposome transport assays. Applying the method to a homology model of PepT1 suggests that the approach requires a high-quality structure to be accurate. Our study provides a blueprint for extending these computational methodologies to other pharmaceutically important transporter families. PMID:27028887

  8. Accurate Prediction of Ligand Affinities for a Proton-Dependent Oligopeptide Transporter

    PubMed Central

    Samsudin, Firdaus; Parker, Joanne L.; Sansom, Mark S.P.; Newstead, Simon; Fowler, Philip W.

    2016-01-01

    Summary Membrane transporters are critical modulators of drug pharmacokinetics, efficacy, and safety. One example is the proton-dependent oligopeptide transporter PepT1, also known as SLC15A1, which is responsible for the uptake of the β-lactam antibiotics and various peptide-based prodrugs. In this study, we modeled the binding of various peptides to a bacterial homolog, PepTSt, and evaluated a range of computational methods for predicting the free energy of binding. Our results show that a hybrid approach (endpoint methods to classify peptides into good and poor binders and a theoretically exact method for refinement) is able to accurately predict affinities, which we validated using proteoliposome transport assays. Applying the method to a homology model of PepT1 suggests that the approach requires a high-quality structure to be accurate. Our study provides a blueprint for extending these computational methodologies to other pharmaceutically important transporter families. PMID:27028887

  9. Horizontally acquired oligopeptide transporters favour adaptation of Saccharomyces cerevisiae wine yeast to oenological environment.

    PubMed

    Marsit, Souhir; Sanchez, Isabelle; Galeote, Virginie; Dequin, Sylvie

    2016-04-01

    In the past decade, horizontal gene transfer (HGT) has emerged as a major evolutionary process that has shaped the genome of Saccharomyces cerevisiae wine yeasts. We recently showed that a large Torulaspora microellipsoides genomic island carrying two oligopeptide transporters encoded by FOT genes increases the fitness of wine yeast during fermentation of grape must. However, the impact of these genes on the metabolic network of S. cerevisiae remained uncharacterized. Here we show that Fot-mediated peptide uptake substantially affects the glutamate node and the NADPH/NADP(+) balance, resulting in the delayed uptake of free amino acids and altered profiles of metabolites and volatile compounds. Transcriptome analysis revealed that cells using a higher amount of oligopeptides from grape must are less stressed and display substantial variation in the expression of genes in the central pathways of carbon and nitrogen metabolism, amino acid and protein biosynthesis, and the oxidative stress response. These regulations shed light on the molecular and metabolic mechanisms involved in the higher performance and fitness conferred by the HGT-acquired FOT genes, pinpointing metabolic effects that can positively affect the organoleptic balance of wines. PMID:26549518

  10. CgOpt1, a putative oligopeptide transporter from Colletotrichum gloeosporioides that is involved in responses to auxin and pathogenicity

    PubMed Central

    2009-01-01

    Background The fungus Colletotrichum gloeosporioides f. sp. aeschynomene produces high levels of indole-3-acetic acid (IAA) in axenic cultures and during plant infection. We generated a suppression subtractive hybridization library enriched for IAA-induced genes and identified a clone, which was highly expressed in IAA-containing medium. Results The corresponding gene showed similarity to oligopeptide transporters of the OPT family and was therefore named CgOPT1. Expression of CgOPT1 in mycelia was low, and was enhanced by external application of IAA. cgopt1-silenced mutants produced less spores, had reduced pigmentation, and were less pathogenic to plants than the wild-type strain. IAA enhanced spore formation and caused changes in colony morphology in the wild-type strain, but had no effect on spore formation or colony morphology of the cgopt1-silenced mutants. Conclusion Our results show that IAA induces developmental changes in C. gloeosporioides. These changes are blocked in cgopt1-silenced mutants, suggesting that this protein is involved in regulation of fungal response to IAA. CgOPT1 is also necessary for full virulence, but it is unclear whether this phenotype is related to auxin. PMID:19698103

  11. The identification of oppA gene homologues as part of the oligopeptide transport system in mycoplasmas.

    PubMed

    Wium, Martha; Botes, Annelise; Bellstedt, Dirk U

    2015-03-01

    The lack of an annotated oppA gene as part of many oligopeptide permease (opp) operons has questioned the necessity of the oligopeptide-binding domain (OppA) as a part of the Opp transport system in mycoplasmas. This study investigated the occurrence of an oppA gene as part of the oppBCDF operon in 42 mycoplasma genomes. Except for hemoplasma, all mycoplasmas were found to possess one or more copies of the oppBCDF operon and with the help of similarity searches their oppA genes could be identified. Phylogenetic analysis of the combined OppABCDF amino acid sequences allowed them to be grouped into three types. Each type has a unique set of conserved motifs, which are likely to reflect substrate preference and adaption strategies. Our approach allowed the identification of oppA gene homologues for all mycoplasma opp operons and thereby provides a method for re-evaluating the current annotation of oppA genes in mycoplasma genomes. PMID:25528211

  12. The Oligopeptide Permease Opp Mediates Illicit Transport of the Bacterial P-site Decoding Inhibitor GE81112 †

    PubMed Central

    Maio, Alessandro; Brandi, Letizia; Donadio, Stefano; Gualerzi, Claudio O.

    2016-01-01

    GE81112 is a tetrapeptide antibiotic that binds to the 30S ribosomal subunit and specifically inhibits P-site decoding of the mRNA initiation codon by the fMet-tRNA anticodon. GE81112 displays excellent microbiological activity against some Gram-positive and Gram-negative bacteria in both minimal and complete, chemically defined, broth, but is essentially inactive in complete complex media. This is due to the presence of peptides that compete with the antibiotic for the oligopeptide permease system (Opp) responsible for its illicit transport into the bacterial cells as demonstrated in the cases of Escherichia coli and Bacillus subtilis. Mutations that inactivate the Opp system and confer GE81112 resistance arise spontaneously with a frequency of ca. 1 × 10−6, similar to that of the mutants resistant to tri-l-ornithine, a known Opp substrate. On the contrary, cells expressing extrachromosomal copies of the opp genes are extremely sensitive to GE81112 in rich medium and GE81112-resistant mutations affecting the molecular target of the antibiotic were not detected upon examining >109 cells of this type. However, some mutations introduced in the 16S rRNA to confer kasugamycin resistance were found to reduce the sensitivity of the cells to GE81112. PMID:27231947

  13. The Oligopeptide Permease Opp Mediates Illicit Transport of the Bacterial P-site Decoding Inhibitor GE81112.

    PubMed

    Maio, Alessandro; Brandi, Letizia; Donadio, Stefano; Gualerzi, Claudio O

    2016-01-01

    GE81112 is a tetrapeptide antibiotic that binds to the 30S ribosomal subunit and specifically inhibits P-site decoding of the mRNA initiation codon by the fMet-tRNA anticodon. GE81112 displays excellent microbiological activity against some Gram-positive and Gram-negative bacteria in both minimal and complete, chemically defined, broth, but is essentially inactive in complete complex media. This is due to the presence of peptides that compete with the antibiotic for the oligopeptide permease system (Opp) responsible for its illicit transport into the bacterial cells as demonstrated in the cases of Escherichia coli and Bacillus subtilis. Mutations that inactivate the Opp system and confer GE81112 resistance arise spontaneously with a frequency of ca. 1 × 10(-6), similar to that of the mutants resistant to tri-l-ornithine, a known Opp substrate. On the contrary, cells expressing extrachromosomal copies of the opp genes are extremely sensitive to GE81112 in rich medium and GE81112-resistant mutations affecting the molecular target of the antibiotic were not detected upon examining >10⁸ cells of this type. However, some mutations introduced in the 16S rRNA to confer kasugamycin resistance were found to reduce the sensitivity of the cells to GE81112. PMID:27231947

  14. Role of the Oligopeptide Permease ABC Transporter of Moraxella catarrhalis in Nutrient Acquisition and Persistence in the Respiratory Tract

    PubMed Central

    Jones, Megan M.; Johnson, Antoinette; Koszelak-Rosenblum, Mary; Kirkham, Charmaine; Brauer, Aimee L.; Malkowski, Michael G.

    2014-01-01

    Moraxella catarrhalis is a strict human pathogen that causes otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults, resulting in significant worldwide morbidity and mortality. M. catarrhalis has a growth requirement for arginine; thus, acquiring arginine is important for fitness and survival. M. catarrhalis has a putative oligopeptide permease ABC transport operon (opp) consisting of five genes (oppB, oppC, oppD, oppF, and oppA), encoding two permeases, two ATPases, and a substrate binding protein. Thermal shift assays showed that the purified recombinant substrate binding protein OppA binds to peptides 3 to 16 amino acid residues in length regardless of the amino acid composition. A mutant in which the oppBCDFA gene cluster is knocked out showed impaired growth in minimal medium where the only source of arginine came from a peptide 5 to 10 amino acid residues in length. Whether methylated arginine supports growth of M. catarrhalis is important in understanding fitness in the respiratory tract because methylated arginine is abundant in host tissues. No growth of wild-type M. catarrhalis was observed in minimal medium in which arginine was present only in methylated form, indicating that the bacterium requires l-arginine. An oppA knockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the Opp system mediates both uptake of peptides and fitness in the respiratory tract. PMID:25156736

  15. Teleost fish models in membrane transport research: the PEPT1(SLC15A1) H+–oligopeptide transporter as a case study

    PubMed Central

    Romano, Alessandro; Barca, Amilcare; Storelli, Carlo; Verri, Tiziano

    2014-01-01

    Human genes for passive, ion-coupled transporters and exchangers are included in the so-called solute carrier (SLC) gene series, to date consisting of 52 families and 398 genes. Teleost fish genes for SLC proteins have also been described in the last two decades, and catalogued in preliminary SLC-like form in 50 families and at least 338 genes after systematic GenBank database mining (December 2010–March 2011). When the kinetic properties of the expressed proteins are studied in detail, teleost fish SLC transporters always reveal extraordinary ‘molecular diversity’ with respect to the mammalian counterparts, which reflects peculiar adaptation of the protein to the physiology of the species and/or to the environment where the species lives. In the case of the H+–oligopeptide transporter PEPT1(SLC15A1), comparative analysis of diverse teleost fish orthologs has shown that the protein may exhibit very eccentric properties in terms of pH dependence (e.g. the adaptation of zebrafish PEPT1 to alkaline pH), temperature dependence (e.g. the adaptation of icefish PEPT1 to sub-zero temperatures) and/or substrate specificity (e.g. the species-specificity of PEPT1 for the uptake of l-lysine-containing peptides). The revelation of such peculiarities is providing new contributions to the discussion on PEPT1 in both basic (e.g. molecular structure–function analyses) and applied research (e.g. optimizing diets to enhance growth of commercially valuable fish). PMID:23981715

  16. OLIGOPEPTIDE TRANSPORTERS AND THEIR ROLE IN FE(II)- AND FE(III)-NICOTIANAMINE TRANSPORT IN RICE (ORYZA SATIVA L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ability of organisms to transport small peptides (two to five amino acids) is wide-ranging, and is present in humans, bacteria, fungi, archaea, and plants. There are three major groups of peptide transporters, divided by their substrate specificity: the ATP binding cassette (ABC), the peptide tr...

  17. Photospintronics: Magnetic Field-Controlled Photoemission and Light-Controlled Spin Transport in Hybrid Chiral Oligopeptide-Nanoparticle Structures.

    PubMed

    Mondal, Prakash Chandra; Roy, Partha; Kim, Dokyun; Fullerton, Eric E; Cohen, Hagai; Naaman, Ron

    2016-04-13

    The combination of photonics and spintronics opens new ways to transfer and process information. It is shown here that in systems in which organic molecules and semiconductor nanoparticles are combined, matching these technologies results in interesting new phenomena. We report on light induced and spin-dependent charge transfer process through helical oligopeptide-CdSe nanoparticles' (NPs) architectures deposited on ferromagnetic substrates with small coercive force (∼100-200 Oe). The spin control is achieved by the application of the chirality-induced spin-dependent electron transfer effect and is probed by two different methods: spin-controlled electrochemichemistry and photoluminescence (PL) at room temperature. The injected spin could be controlled by excitation of the nanoparticles. By switching the direction of the magnetic field of the substrate, the PL intensity could be alternated. PMID:27027885

  18. Gating Topology of the Proton-Coupled Oligopeptide Symporters

    PubMed Central

    Fowler, Philip W.; Orwick-Rydmark, Marcella; Radestock, Sebastian; Solcan, Nicolae; Dijkman, Patricia M.; Lyons, Joseph A.; Kwok, Jane; Caffrey, Martin; Watts, Anthony; Forrest, Lucy R.; Newstead, Simon

    2015-01-01

    Summary Proton-coupled oligopeptide transporters belong to the major facilitator superfamily (MFS) of membrane transporters. Recent crystal structures suggest the MFS fold facilitates transport through rearrangement of their two six-helix bundles around a central ligand binding site; how this is achieved, however, is poorly understood. Using modeling, molecular dynamics, crystallography, functional assays, and site-directed spin labeling combined with double electron-electron resonance (DEER) spectroscopy, we present a detailed study of the transport dynamics of two bacterial oligopeptide transporters, PepTSo and PepTSt. Our results identify several salt bridges that stabilize outward-facing conformations and we show that, for all the current structures of MFS transporters, the first two helices of each of the four inverted-topology repeat units form half of either the periplasmic or cytoplasmic gate and that these function cooperatively in a scissor-like motion to control access to the peptide binding site during transport. PMID:25651061

  19. Dynamics of an antibiotic oligopeptide

    NASA Astrophysics Data System (ADS)

    Middendorf, H. D.; Alves, N.; Zanotti, J.-M.; Gomes, P.; Bastos, M.

    2006-11-01

    Neutron time-of-flight spectra were measured for an H 2O-hydrated and a nominally dry sample of a 15-residue antibacterial oligopeptide from 99 to 271 K. Proton mobilities, quasielastic broadenings, and changes in low-frequency inelastic intensities characterise the evolution of the peptide energy landscape as a function of momentum transfer and temperature.

  20. Prevention of skeletal muscle atrophy in vitro using anti-ubiquitination oligopeptide carried by atelocollagen.

    PubMed

    Kawai, Nobuhiko; Hirasaka, Katsuya; Maeda, Tasuku; Haruna, Marie; Shiota, Chieko; Ochi, Arisa; Abe, Tomoki; Kohno, Shohei; Ohno, Ayako; Teshima-Kondo, Sigetada; Mori, Hiroyo; Tanaka, Eiji; Nikawa, Takeshi

    2015-05-01

    Skeletal muscle atrophy occurs when the rate of protein degradation exceeds that of protein synthesis in various catabolic conditions, such as fasting, disuse, aging, and chronic diseases. Insulin-like growth factor-1 (IGF-1) signaling stimulates muscle growth and suppresses muscle protein breakdown. In atrophied muscles, ubiquitin ligase, Cbl-b, increases and stimulates the ubiquitination and degradation of IRS-1, an intermediate in IGF-1 signaling pathway, resulting in IGF-1 resistance. In this study, we evaluated the efficacy of atelocollagen (ATCOL)-transported anti-ubiquitination oligopeptide (Cblin: Cbl-b inhibitor) (consisting of tyrosine phosphorylation domain of IRS-1) in starved C2C12 myotubes. The amount of IRS-1 protein was lower in starved versus unstarved myotubes. The Cblin-ATCOL complex inhibited IRS-1 degradation in a concentration-dependent manner. Myotubes incubated with Cblin-ATCOL complex showed significant resistance to starvation-induced atrophy (p<0.01). Furthermore, the Cblin-ATCOL complex significantly inhibited any decrease in Akt phosphorylation (p<0.01) and localization of FOXO3a to the nucleus in starved myotubes. These results suggest that Cblin prevented starvation-induced C2C12 myotube atrophy by maintaining the IGF-1/Akt/FOXO signaling. Therefore, attachment of anti-ubiquitination oligopeptide, Cblin, to ATCOL enhances its delivery to myotubes and could be a potentially effective strategy in the treatment of atrophic myopathies. PMID:25667084

  1. TcOPT3, a Member of Oligopeptide Transporters from the Hyperaccumulator Thlaspi caerulescens, Is a Novel Fe/Zn/Cd/Cu Transporter

    PubMed Central

    Hu, Yi Ting; Ming, Feng; Chen, Wei Wei; Yan, Jing Ying; Xu, Zheng Yu; Li, Gui Xin; Xu, Chun Yan; Yang, Jian Li; Zheng, Shao Jian

    2012-01-01

    Background Thlaspi caerulescens is a natural selected heavy metal hyperaccumulator that can not only tolerate but also accumulate extremely high levels of heavy metals in the shoots. Thus, to identify the transportors involved in metal long-distance transportation is very important for understanding the mechanism of heavy metal accumulation in this hyperaccumulator. Methodology/Principal Findings We cloned and characterized a novel gene TcOPT3 of OPT family from T. caerulescens. TcOPT3 was pronouncedly expressed in aerial parts, including stem and leaf. Moreover, in situ hybridization analyses showed that TcOPT3 expressed in the plant vascular systems, especially in the pericycle cells that may be involved in the long-distance transportation. The expression of TcOPT3 was highly induced by iron (Fe) and zinc (Zn) deficiency, especially in the stem and leaf. Sub-cellular localization showed that TcOPT3 was a plasma membrane-localized protein. Furthermore, heterogonous expression of TcOPT3 by mutant yeast (Saccharomyces cerevisiae) complementation experiments demonstrated that TcOPT3 could transport Fe2+ and Zn2+. Moreover, expression of TcOPT3 in yeast increased metal (Fe, Zn, Cu and Cd) accumulation and resulted in an increased sensitivity to cadmium (Cd) and copper (Cu). Conclusions Our data demonstrated that TcOPT3 might encode an Fe/Zn/Cd/Cu influx transporter with broad-substrate. This is the first report showing that TcOPT3 may be involved in metal long-distance transportation and contribute to the heavy metal hyperaccumulation. PMID:22761683

  2. Electronic structure analysis of glycine oligopeptides and glycine-tryptophan oligopeptides

    NASA Astrophysics Data System (ADS)

    Li, Xin; Yu, Shuai; Yang, Mengshi; Xu, Can; Wang, Yu; Chen, Liang

    2014-03-01

    Using the density functional theory (DFT), we have studied the energy gap, charge distribution, density of states and chemical activity of glycine (Gn) oligopeptides and glycine-tryptophan (GWn) oligopeptides. The results show that: (1) with the increasing of Gn residues, the chemical activity of Gn oligopeptides focuses on the terminal amino and carboxyl groups, which may be the main cause of self-assembly behaviors in Gn oligopeptide chains; (2) the chemical reaction activity has size effect. The size effect disappears when the residue number exceeds 7. The Gn oligopeptides with 7 residues is the shortest chain which has the same reaction activity as that of longer size peptide; (3) the activity of GWn oligopeptides presents size effect and odd-even effect. However, the size effect and odd-even effect both vanish when the chain of GWn oligopeptides is longer than 12 residues. (4) It is difficult in self-assembly for GWn oligopeptide chains, because its activity mainly focuses on the indole ring and the Gn residues at the end of oligopeptides. (5) The big side groups result in the very near energy level of LUMO and LUMO+1 of GWn oligopeptide chains. It shows that the electron-accepting ability of oligopeptide chainsis composed of two orbitals addition. The results in the paper may help us understand the changes of physical and chemical properties of peptide synthesis process.

  3. Collective microdynamics and noise suppression in dispersive electron beam transport

    SciTech Connect

    Gover, Avraham; Dyunin, Egor; Duchovni, Tamir; Nause, Ariel

    2011-12-15

    A general formulation is presented for deep collective interaction micro-dynamics in dispersive e-beam transport. In the regime of transversely coherent interaction, the formulation is applicable to both coherent and random temporal modulation of the electron beam. We demonstrate its use for determining the conditions for suppressing beam current noise below the classical shot-noise level by means of transport through a dispersive section with a small momentum compaction parameter.

  4. Suppression of turbulence and transport by sheared flow

    SciTech Connect

    Terry, P. W.

    2000-01-01

    The role of stable shear flow in suppressing turbulence and turbulent transport in plasmas and neutral fluids is reviewed. Localized stable flow shear produces transport barriers whose extensive and highly successful utilization in fusion devices has made them the primary experimental technique for reducing and even eliminating the rapid turbulent losses of heat and particles that characterize fusion-grade plasmas. These transport barriers occur in different plasma regions with disparate physical properties and in a range of confining configurations, indicating a physical process of unusual universality. Flow shear suppresses turbulence by speeding up turbulent decorrelation. This is a robust feature of advection whenever the straining rate of stable mean flow shear exceeds the nonlinear decorrelation rate. Shear straining lowers correlation lengths in the direction of shear and reduces turbulent amplitudes. It also disrupts other processes that feed into or result from turbulence, including the linear instability of important collective modes, the transport-producing correlations between advecting fluid and advectants, and large-scale spatially connected avalanchelike transport events. In plasmas, regions of stable flow shear can be externally driven, but most frequently are created spontaneously in critical transitions between different plasma states. Shear suppression occurs in hydrodynamics and represents an extension of rapid-distortion theory to a long-time-scale nonlinear regime in two-dimensional stable shear flow. Examples from hydrodynamics include the emergence of coherent vortices in decaying two-dimensional Navier-Stokes turbulence and the reduction of turbulent transport in the stratosphere. (c) 2000 The American Physical Society.

  5. Suppression of turbulent transport in NSTX internal transport barriers

    NASA Astrophysics Data System (ADS)

    Yuh, Howard

    2008-11-01

    Electron transport will be important for ITER where fusion alphas and high-energy beam ions will primarily heat electrons. In the NSTX, internal transport barriers (ITBs) are observed in reversed (negative) shear discharges where diffusivities for electron and ion thermal channels and momentum are reduced. While neutral beam heating can produce ITBs in both electron and ion channels, High Harmonic Fast Wave (HHFW) heating can produce electron thermal ITBs under reversed magnetic shear conditions without momentum input. Interestingly, the location of the electron ITB does not necessarily match that of the ion ITB: the electron ITB correlates well with the minimum in the magnetic shear determined by Motional Stark Effect (MSE) [1] constrained equilibria, whereas the ion ITB better correlates with the maximum ExB shearing rate. Measured electron temperature gradients can exceed critical linear thresholds for ETG instability calculated by linear gyrokinetic codes in the ITB confinement region. The high-k microwave scattering diagnostic [2] shows reduced local density fluctuations at wavenumbers characteristic of electron turbulence for discharges with strongly negative magnetic shear versus weakly negative or positive magnetic shear. Fluctuation reductions are found to be spatially and temporally correlated with the local magnetic shear. These results are consistent with non-linear gyrokinetic simulations predictions showing the reduction of electron transport in negative magnetic shear conditions despite being linearly unstable [3]. Electron transport improvement via negative magnetic shear rather than ExB shear highlights the importance of current profile control in ITER and future devices. [1] F.M. Levinton, H. Yuh et al., PoP 14, 056119 [2] D.R. Smith, E. Mazzucato et al., RSI 75, 3840 [3] Jenko, F. and Dorland, W., PRL 89 225001

  6. Synthesis of analogs of L-valacyclovir and determination of their substrate activity for the oligopeptide transporter in Caco-2 cells.

    PubMed

    Friedrichsen, Gerda Marie; Chen, Weiqing; Begtrup, Mikael; Lee, Chao-Pin; Smith, Philip L; Borchardt, Ronald T

    2002-07-01

    L-Valacyclovir, a prodrug of acyclovir, is a substrate for the peptide transporter (PepT1) in the intestinal mucosa, which accounts for its higher than expected oral bioavailability. The substrate activity of L-valacyclovir for PepT1 is surprising, particularly when one considers that the molecule has the structural features of a nucleoside rather than a peptide. In an attempt to better understand the structure-transport relationships (STR) for the interactions of L-valacyclovir with PepT1, analogs of this molecule with structural changes in the guanine moiety were synthesized and their substrate activity for PepT1 in Caco-2 cell monolayers was determined. The analogs synthesized include those that had the guanine moiety of L-valacyclovir substituted with purine, benzimidazole, and 7-azaindole. All three analogs (purine, benzimidazole, and 7-azaindole) exhibited affinity for PepT1 in binding studies, but only the purine analog (as the L-valine ester) showed PepT1-associated transcellular transport across Caco-2 cell monolayers. The benzimidazole and 7-azaindole analogs (as their L-valine esters) were rapidly metabolized by esterase when applied to the apical surface of Caco-2 cells, which probably explains their low penetration as the intact prodrugs via PepT1. PMID:12113886

  7. SUPPRESSION OF ENERGETIC ELECTRON TRANSPORT IN FLARES BY DOUBLE LAYERS

    SciTech Connect

    Li, T. C.; Drake, J. F.; Swisdak, M.

    2012-09-20

    During flares and coronal mass ejections, energetic electrons from coronal sources typically have very long lifetimes compared to the transit times across the systems, suggesting confinement in the source region. Particle-in-cell simulations are carried out to explore the mechanisms of energetic electron transport from the corona to the chromosphere and possible confinement. We set up an initial system of pre-accelerated hot electrons in contact with ambient cold electrons along the local magnetic field and let it evolve over time. Suppression of transport by a nonlinear, highly localized electrostatic electric field (in the form of a double layer) is observed after a short phase of free-streaming by hot electrons. The double layer (DL) emerges at the contact of the two electron populations. It is driven by an ion-electron streaming instability due to the drift of the back-streaming return current electrons interacting with the ions. The DL grows over time and supports a significant drop in temperature and hence reduces heat flux between the two regions that is sustained for the duration of the simulation. This study shows that transport suppression begins when the energetic electrons start to propagate away from a coronal acceleration site. It also implies confinement of energetic electrons with kinetic energies less than the electrostatic energy of the DL for the DL lifetime, which is much longer than the electron transit time through the source region.

  8. The Ubiquitin Ligase Ubr11 Is Essential for Oligopeptide Utilization in the Fission Yeast Schizosaccharomyces pombe

    PubMed Central

    Nakase, Mai; Tohda, Hideki; Takegawa, Kaoru

    2012-01-01

    Uptake of extracellular oligopeptides in yeast is mediated mainly by specific transporters of the peptide transporter (PTR) and oligopeptide transporter (OPT) families. Here, we investigated the role of potential peptide transporters in the yeast Schizosaccharomyces pombe. Utilization of naturally occurring dipeptides required only Ptr2/SPBC13A2.04c and none of the other 3 OPT proteins (Isp4, Pgt1, and Opt3), whereas only Isp4 was indispensable for tetrapeptide utilization. Both Ptr2 and Isp4 localized to the cell surface, but under rich nutrient conditions Isp4 localized in the Golgi apparatus through the function of the ubiquitin ligase Pub1. Furthermore, the ubiquitin ligase Ubr11 played a significant role in oligopeptide utilization. The mRNA levels of both the ptr2 and isp4 genes were significantly reduced in ubr11Δ cells, and the dipeptide utilization defect in the ubr11Δ mutant was rescued by the forced expression of Ptr2. Consistent with its role in transcriptional regulation of peptide transporter genes, the Ubr11 protein was accumulated in the nucleus. Unlike the situation in Saccharomyces cerevisiae, the oligopeptide utilization defect in the S. pombe ubr11Δ mutant was not rescued by inactivation of the Tup11/12 transcriptional corepressors, suggesting that the requirement for the Ubr ubiquitin ligase in the upregulation of peptide transporter mRNA levels is conserved in both yeasts; however, the actual mechanism underlying the control appears to be different. We also found that the peptidomimetic proteasome inhibitor MG132 was still operative in a strain lacking all known PTR and OPT peptide transporters. Therefore, irrespective of its peptide-like structure, MG132 is carried into cells independently of the representative peptide transporters. PMID:22226946

  9. A toolbox of oligopeptide-modified polymers for tailored elastomers.

    PubMed

    Croisier, Emmanuel; Liang, Su; Schweizer, Thomas; Balog, Sandor; Mionić, Marijana; Snellings, Ruben; Cugnoni, Joël; Michaud, Véronique; Frauenrath, Holger

    2014-01-01

    Biomaterials are constructed from limited sets of building blocks but exhibit extraordinary and versatile properties, because hierarchical structure formation lets them employ identical supramolecular motifs for different purposes. Here we exert a similar degree of structural control in synthetic supramolecular elastomers and thus tailor them for a broad range of thermomechanical properties. We show that oligopeptide-terminated polymers selectively self-assemble into small aggregates or nanofibrils, depending on the length of the oligopeptides. This process is self-sorting if differently long oligopeptides are combined so that different nanostructures coexist in bulk mixtures. Blends of polymers with oligopeptides matching in length furnish reinforced elastomers that exhibit shear moduli one order of magnitude higher than the parent polymers. By contrast, novel interpenetrating supramolecular networks that display excellent vibration damping properties are obtained from blends comprising non-matching oligopeptides or unmodified polymers. Hence, blends of oligopeptide-modified polymers constitute a toolbox for tailored elastomers with versatile properties. PMID:25198134

  10. Identification of a novel compound that inhibits osteoclastogenesis by suppressing nucleoside transporters.

    PubMed

    Katsuyama, Shun; Sugino, Kumi; Sasazawa, Yukiko; Nakano, Yoshihiko; Aono, Harumi; Morishita, Keisuke; Kawatani, Makoto; Umezawa, Kazuo; Osada, Hiroyuki; Simizu, Siro

    2016-04-01

    We screened small-molecule compounds that inhibit osteoclast differentiation to find new anti-osteoporosis agents and found that a novel compound, SUKU-1, suppressed osteoclastogenesis. We also synthesized 38 derivatives of SUKU-1 and discovered that nine of them had inhibitory effects on osteoclastogenesis and that SUKU-33 was the most potent inhibitor. Next, we investigated the mechanisms by which SUKU-33 suppressed osteoclast differentiation. By measuring the uptake of [(3) H]-uridine in cells, we found that SUKU-33 suppressed both equilibrative nucleoside transporters and concentrative nucleoside transporters. These results suggest that SUKU-33 inhibits osteoclast differentiation by suppressing nucleoside transporters. PMID:27001232

  11. In Silico Approach towards Designing Virtual Oligopeptides for HRSV

    PubMed Central

    Jain, Ruchi; Piramanayagam, Shanmughavel

    2014-01-01

    HRSV (human respiratory syncytial virus) is a serious cause of lower respiratory tract illness in infants and young children. Designing inhibitors from the proteins involved in virus replication and infection process provides target for new therapeutic treatments. In the present study, in silico docking was performed using motavizumab as a template to design motavizumab derived oligopeptides for developing novel anti-HRSV agents. Additional simulations were conducted to study the conformational propensities of the oligopeptides and confirmed the hypothesis that the designed oligopeptide is highly flexible and capable of assuming stable confirmation. Our study demonstrated the best specific interaction of GEKKLVEAPKS oligopeptide for glycoprotein strain A among various screened oligopeptides. Encouraged by the results, we expect that the proposed scheme will provide rational choices for antibody reengineering which is useful for systematically identifying the possible ways to improve efficacy of existing antibody drugs. PMID:25525622

  12. Non-Statistical Oligopeptide Fragmentation by IR Photons with λ=16-18 μm

    NASA Astrophysics Data System (ADS)

    Jungclas, Hartmut; Komarov, Viacheslav V.; Popova, Anna M.; Schmidt, Lothar

    2015-12-01

    In this article we analyse the vibration excitation and following dissociation of protonated oligopeptide molecules induced by IR photons with λ=16-18 μm. The analysis is based on our previous works in which we considered a specific non-statistical dissociation process in organic molecules containing substructures consisting of chained identical diatomic dipoles such as (CH2)n. Such dipole chains can serve as IR antennas for external radiation in the IR frequency range. The acquired vibration energy accumulated in IR antennas can be large enough to dissociate molecules within a femtosecond time interval by a non-statistical process, which is driven by a radiationless low-energy transport mechanism inside the peptide molecules. We point out in this article that the suggested IR-induced dissociation mechanism can be applied to obtain sequence information of protonated oligopeptides.

  13. Effect of grafted oligopeptides on friction.

    PubMed

    Iarikov, Dmitri D; Ducker, William A

    2013-05-14

    Frictional and normal forces in aqueous solution at 25 °C were measured between a glass particle and oligopeptide films grafted from a glass plate. Homopeptide molecules consisting of 11 monomers of either glutamine, leucine, glutamic acid, lysine, or phenylalanine and one heteropolymer were each "grafted from" an oxidized silicon wafer using microwave-assisted solid-phase peptide synthesis. The peptide films were characterized using X-ray photoelectron spectroscopy and secondary ion mass spectrometry. Frictional force measurements showed that the oligopeptides increased the magnitude of friction compared to that on a bare hydrophilic silicon wafer but that the friction was a strong function of the nature of the monomer unit. Overall we find that the friction is lower for more hydrophilic films. For example, the most hydrophobic monomer, leucine, exhibited the highest friction whereas the hydrophilic monomer, polyglutamic acid, exhibited the lowest friction at zero load. When the two surfaces had opposite charges, there was a strong attraction, adhesion, and high friction between the surfaces. Friction for all polymers was lower in phosphate-buffered saline than in pure water, which was attributed to lubrication via hydrated salt ions. PMID:23594080

  14. Characterization and Evaluation of the Moraxella catarrhalis Oligopeptide Permease A as a Mucosal Vaccine Antigen▿

    PubMed Central

    Yang, Min; Johnson, Antoinette; Murphy, Timothy F.

    2011-01-01

    Moraxella catarrhalis is a common cause of otitis media in children and of lower respiratory tract infections in adults with chronic obstructive pulmonary disease; therefore, these two groups would benefit from a vaccine to prevent M. catarrhalis infections. A genome mining approach for vaccine antigens identified oligopeptide permease protein A (OppA), an oligopeptide binding protein of an apparent oligopeptide transport system. Analysis of the oppA gene by PCR and sequence analysis revealed that OppA is highly conserved among clinical isolates of M. catarrhalis. Recombinant OppA was expressed as a lipoprotein and purified, and an oppA knockout mutant was constructed. Antiserum raised to recombinant purified OppA recognized epitopes on the bacterial surface of the wild type but not the OppA knockout mutant. Antibodies raised to purified recombinant OppA recognized native OppA in multiple strains. Intranasal immunization of mice induced systemic and mucosal antibodies to OppA and resulted in enhanced clearance of M. catarrhalis in a mouse pulmonary clearance model. OppA is a highly conserved, immunogenic protein that expresses epitopes on the bacterial surface and that induces potentially protective immune responses in a mouse model. OppA should be evaluated further as a vaccine antigen for M. catarrhalis. PMID:21134967

  15. Formation of oligopeptides in high yield under simple programmable conditions

    PubMed Central

    Rodriguez-Garcia, Marc; Surman, Andrew J.; Cooper, Geoffrey J.T.; Suárez-Marina, Irene; Hosni, Zied; Lee, Michael P.; Cronin, Leroy

    2015-01-01

    Many high-yielding reactions for forming peptide bonds have been developed but these are complex, requiring activated amino-acid precursors and heterogeneous supports. Herein we demonstrate the programmable one-pot dehydration–hydration condensation of amino acids forming oligopeptide chains in around 50% yield. A digital recursive reactor system was developed to investigate this process, performing these reactions with control over parameters such as temperature, number of cycles, cycle duration, initial monomer concentration and initial pH. Glycine oligopeptides up to 20 amino acids long were formed with very high monomer-to-oligomer conversion, and the majority of these products comprised three amino acid residues or more. Having established the formation of glycine homo-oligopeptides, we then demonstrated the co-condensation of glycine with eight other amino acids (Ala, Asp, Glu, His, Lys, Pro, Thr and Val), incorporating a range of side-chain functionality. PMID:26442968

  16. The Suppression of Energy Discretization Errors in Multigroup Transport Calculations

    SciTech Connect

    Larsen, Edward

    2013-06-17

    The Objective of this project is to develop, implement, and test new deterministric methods to solve, as efficiently as possible, multigroup neutron transport problems having an extremely large number of groups. Our approach was to (i) use the standard CMFD method to "coarsen" the space-angle grid, yielding a multigroup diffusion equation, and (ii) use a new multigrid-in-space-and-energy technique to efficiently solve the multigroup diffusion problem. The overall strategy of (i) how to coarsen the spatial an energy grids, and (ii) how to navigate through the various grids, has the goal of minimizing the overall computational effort. This approach yields not only the fine-grid solution, but also coarse-group flux-weighted cross sections that can be used for other related problems.

  17. Transport enhancement and suppression in turbulent magnetic reconnection: A self-consistent turbulence model

    SciTech Connect

    Yokoi, N.; Higashimori, K.; Hoshino, M.

    2013-12-15

    Through the enhancement of transport, turbulence is expected to contribute to the fast reconnection. However, the effects of turbulence are not so straightforward. In addition to the enhancement of transport, turbulence under some environment shows effects that suppress the transport. In the presence of turbulent cross helicity, such dynamic balance between the transport enhancement and suppression occurs. As this result of dynamic balance, the region of effective enhanced magnetic diffusivity is confined to a narrow region, leading to the fast reconnection. In order to confirm this idea, a self-consistent turbulence model for the magnetic reconnection is proposed. With the aid of numerical simulations where turbulence effects are incorporated in a consistent manner through the turbulence model, the dynamic balance in the turbulence magnetic reconnection is confirmed.

  18. Effects of phenylalanine and threonine oligopeptides on milk protein synthesis in cultured bovine mammary epithelial cells.

    PubMed

    Zhou, M M; Wu, Y M; Liu, H Y; Liu, J X

    2015-04-01

    This study was conducted to investigate the effects of phenylalanine (Phe) and threonine (Thr) oligopeptides on αs1 casein gene expression and milk protein synthesis in bovine mammary epithelial cells. Primary mammary epithelial cells were obtained from Holstein dairy cows and incubated in Dulbecco's modified Eagle's medium-F12 medium (DMEM/F12) containing lactogenic hormones (prolactin and glucocorticoids). Free Phe (117 μg/ml) was substituted partly with peptide-bound Phe (phenylalanylphenylalanine, phenylalanyl threonine, threonyl-phenylalanyl-phenylalanine) in the experimental media. After incubation with experimental medium, cells were collected for gene expression analysis and medium was collected for milk protein or amino acid determination. The results showed that peptide-bound Phe at 10% (11.7 μg/ml) significantly enhanced αs1 casein gene expression and milk protein synthesis as compared with equivalent amount of free Phe. When 10% Phe was replaced by phenylalanylphenylalanine, the disappearance of most essential amino acids increased significantly, and gene expression of peptide transporter 2 and some amino acid transporters was significantly enhanced. These results indicate that the Phe and Thr oligopeptides are important for milk protein synthesis, and peptide-bound amino acids could be utilised more efficiently in milk protein synthesis than the equivalent amount of free amino acids. PMID:25199802

  19. Effects of oligopeptide permease in group a streptococcal infection.

    PubMed

    Wang, Chih-Hung; Lin, Chia-Yu; Luo, Yueh-Hsia; Tsai, Pei-Jane; Lin, Yee-Shin; Lin, Ming T; Chuang, Woei-Jer; Liu, Ching-Chuan; Wu, Jiunn-Jong

    2005-05-01

    The oligopeptide permease (Opp) of group A streptococci (GAS) is a membrane-associated protein and belongs to the ATP-binding cassette transporter family. It is encoded by a polycistronic operon containing oppA, oppB, oppC, oppD, and oppF. The biological function of these genes in GAS is poorly understood. In order to understand more about the effects of Opp on GAS virulence factors, an oppA isogenic mutant was constructed by using an integrative plasmid to disrupt the opp operon and confirmed by Southern blot hybridization. No transcript was detected in the oppA isogenic mutant by Northern blot analysis and reverse transcriptase PCR. The growth curve for the oppA isogenic mutant was similar to that for wild-type strain A-20. The oppA isogenic mutant not only decreased the transcription of speB, speX, and rofA but also increased the transcription of speF, sagA (streptolysin S-associated gene A), slo (streptolysin O), pel (pleotrophic effect locus), and dppA (dipeptide permease). No effects on the transcription of emm, sda, speJ, speG, rgg, and csrR were found. The phenotypes of the oppA mutant were restored by the oppA revertant and by the complementation strain. The oppA mutant caused less mortality and tissue damage than the wild-type strain when inoculated into BALB/c mice via an air pouch. Based on these data, we suggest that the opp operon plays an important role in the pathogenesis of GAS infection. PMID:15845494

  20. Suppression of Residual Sloshing in a Liquid Transport Container by a Bulkhead

    NASA Astrophysics Data System (ADS)

    Onuma, Ryu; Watanabe, Masahiro; Tanaka, Hideaki

    This paper deals with an experimental study on suppression of a residual sloshing in a liquid transport container by a bulkhead, which divides the container vertically into two sections. Inserting the bulkhead to the container, the sloshing mode is separated into two modes; the one is the sloshing mode of liquid column in a U-tube (U-tube-mode), and the other is the sloshing mode in the separated container (Bulkhead-mode). In this paper, the suppression effect by the bulkhead on residual sloshing, which is excited by sudden stop of the liquid transport container, is examined experimentally with changing aperture ratio of the bulkhead, types of the bulkhead plate with or without holes, and the size of holes. Moreover, the fluid flow in the container is visualized and the suppression mechanism by the bulkhead is discussed based on the flow visualization. As a result, detailed suppression effect by the bulkhead on the residual sloshing is clarified, and it is clarified that higher suppression effect by the bulkhead is caused by the energy dissipation due to the vortex generated at the edge of the bulkhead and swirl flow in the liquid. The vortex generated and swirl flow in the liquid play an important role in higher energy dissipation of sloshing.

  1. Oligopeptides as Biomarkers of Cyanobacterial Subpopulations. Toward an Understanding of Their Biological Role

    PubMed Central

    Agha, Ramsy; Quesada, Antonio

    2014-01-01

    Cyanobacterial oligopeptides comprise a wide range of bioactive and/or toxic compounds. While current research is strongly focused on exploring new oligopeptide variants and their bioactive properties, the biological role of these compounds remains elusive. Oligopeptides production abilities show a remarkably patchy distribution among conspecific strains. This observation has prompted alternative approaches to unveil their adaptive value, based on the use of cellular oligopeptide compositions as biomarkers of intraspecific subpopulations or chemotypes in freshwater cyanobacteria. Studies addressing the diversity, distribution, and dynamics of chemotypes in natural systems have provided important insights into the structure and ecology of cyanobacterial populations and the adaptive value of oligopeptides. This review presents an overview of the fundamentals of this emerging approach and its most relevant findings, and discusses our current understanding of the role of oligopeptides in the ecology of cyanobacteria. PMID:24960202

  2. 30 CFR 75.1911 - Fire suppression systems for diesel-powered equipment and fuel transportation units.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... secured computer system that is not susceptible to alteration. (3) Records shall be maintained at a... transportation units. (a) The fire suppression system required by §§ 75.1907 and 75.1909 shall be a multipurpose dry chemical type (ABC) fire suppression system listed or approved by a nationally...

  3. 30 CFR 75.1911 - Fire suppression systems for diesel-powered equipment and fuel transportation units.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... secured computer system that is not susceptible to alteration. (3) Records shall be maintained at a... transportation units. (a) The fire suppression system required by §§ 75.1907 and 75.1909 shall be a multipurpose dry chemical type (ABC) fire suppression system listed or approved by a nationally...

  4. 30 CFR 75.1911 - Fire suppression systems for diesel-powered equipment and fuel transportation units.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... secured computer system that is not susceptible to alteration. (3) Records shall be maintained at a... transportation units. (a) The fire suppression system required by §§ 75.1907 and 75.1909 shall be a multipurpose dry chemical type (ABC) fire suppression system listed or approved by a nationally...

  5. 30 CFR 75.1911 - Fire suppression systems for diesel-powered equipment and fuel transportation units.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... secured computer system that is not susceptible to alteration. (3) Records shall be maintained at a... transportation units. (a) The fire suppression system required by §§ 75.1907 and 75.1909 shall be a multipurpose dry chemical type (ABC) fire suppression system listed or approved by a nationally...

  6. Localized Turbulence Suppression and Increased Flow Shear near the q=2 Surface during Internal-Transport-Barrier Formation

    SciTech Connect

    Shafer, M. W.; McKee, G. R.; Fonck, R. J.; Schlossberg, D. J.; Austin, M. E.; Burrell, K. H.

    2009-08-14

    Broadband turbulent fluctuations in the plasma density are transiently suppressed when low-order rational q surfaces first appear in negative central magnetic shear plasmas on the DIII-D tokamak, which can lead to the formation of internal transport barriers. Increased localized flow shear is simultaneously observed. It transiently exceeds the measured turbulence decorrelation rate, providing a mechanism to trigger the formation of the transport barrier. This increased flow shear and turbulence suppression propagates radially outward, following the q=2 surface.

  7. Nonvesicular Release of Glutamate by Glial xCT Transporters Suppresses Glutamate Receptor Clustering In Vivo

    PubMed Central

    Augustin, Hrvoje; Grosjean, Yael; Chen, Kaiyun; Sheng, Qi; Featherstone, David E.

    2008-01-01

    We hypothesized that cystine/glutamate transporters (xCTs) might be critical regulators of ambient extracellular glutamate levels in the nervous system and that misregulation of this glutamate pool might have important neurophysiological and/or behavioral consequences. To test this idea, we identified and functionally characterized a novel Drosophila xCT gene, which we subsequently named “genderblind” (gb). Genderblind is expressed in a previously overlooked subset of peripheral and central glia. Genetic elimination of gb causes a 50% reduction in extracellular glutamate concentration, demonstrating that xCT transporters are important regulators of extracellular glutamate. Consistent with previous studies showing that extracellular glutamate regulates postsynaptic glutamate receptor clustering, gb mutants show a large (200–300%) increase in the number of postsynaptic glutamate receptors. This increase in postsynaptic receptor abundance is not accompanied by other obvious synaptic changes and is completely rescued when synapses are cultured in wild-type levels of glutamate. Additional in situ pharmacology suggests that glutamate-mediated suppression of glutamate receptor clustering depends on receptor desensitization. Together, our results suggest that (1) xCT transporters are critical for regulation of ambient extracellular glutamate in vivo; (2) ambient extracellular glutamate maintains some receptors constitutively desensitized in vivo; and (3) constitutive desensitization of ionotropic glutamate receptors suppresses their ability to cluster at synapses. PMID:17202478

  8. Chemical Interference with Iron Transport Systems to Suppress Bacterial Growth of Streptococcus pneumoniae

    PubMed Central

    Zhang, Liang; Li, Nan; Han, Junlong; Zhang, Jing; Sun, Xuesong; He, Qing-Yu

    2014-01-01

    Iron is an essential nutrient for the growth of most bacteria. To obtain iron, bacteria have developed specific iron-transport systems located on the membrane surface to uptake iron and iron complexes such as ferrichrome. Interference with the iron-acquisition systems should be therefore an efficient strategy to suppress bacterial growth and infection. Based on the chemical similarity of iron and ruthenium, we used a Ru(II) complex R-825 to compete with ferrichrome for the ferrichrome-transport pathway in Streptococcus pneumoniae. R-825 inhibited the bacterial growth of S. pneumoniae and stimulated the expression of PiuA, the iron-binding protein in the ferrichrome-uptake system on the cell surface. R-825 treatment decreased the cellular content of iron, accompanying with the increase of Ru(II) level in the bacterium. When the piuA gene (SPD_0915) was deleted in the bacterium, the mutant strain became resistant to R-825 treatment, with decreased content of Ru(II). Addition of ferrichrome can rescue the bacterial growth that was suppressed by R-825. Fluorescence spectral quenching showed that R-825 can bind with PiuA in a similar pattern to the ferrichrome-PiuA interaction in vitro. These observations demonstrated that Ru(II) complex R-825 can compete with ferrichrome for the ferrichrome-transport system to enter S. pneumoniae, reduce the cellular iron supply, and thus suppress the bacterial growth. This finding suggests a novel antimicrobial approach by interfering with iron-uptake pathways, which is different from the mechanisms used by current antibiotics. PMID:25170896

  9. Suppression of Arbuscule Degeneration in Medicago truncatula phosphate transporter4 Mutants Is Dependent on the Ammonium Transporter 2 Family Protein AMT2;3

    PubMed Central

    Breuillin-Sessoms, Florence; Floss, Daniela S.; Gomez, S. Karen; Pumplin, Nathan; Ding, Yi; Levesque-Tremblay, Veronique; Noar, Roslyn D.; Daniels, Dierdra A.; Bravo, Armando; Eaglesham, James B.; Benedito, Vagner A.; Udvardi, Michael K.; Harrison, Maria J.

    2015-01-01

    During arbuscular mycorrhizal (AM) symbiosis, the plant gains access to phosphate (Pi) and nitrogen delivered by its fungal symbiont. Transfer of mineral nutrients occurs at the interface between branched hyphae called arbuscules and root cortical cells. In Medicago truncatula, a Pi transporter, PT4, is required for symbiotic Pi transport, and in pt4, symbiotic Pi transport fails, arbuscules degenerate prematurely, and the symbiosis is not maintained. Premature arbuscule degeneration (PAD) is suppressed when pt4 mutants are nitrogen-deprived, possibly the result of compensation by PT8, a second AM-induced Pi transporter. However, PAD is also suppressed in nitrogen-starved pt4 pt8 double mutants, negating this hypothesis and furthermore indicating that in this condition, neither of these symbiotic Pi transporters is required for symbiosis. In M. truncatula, three AMT2 family ammonium transporters are induced during AM symbiosis. To test the hypothesis that suppression of PAD involves AMT2 transporters, we analyzed double and triple Pi and ammonium transporter mutants. ATM2;3 but not AMT2;4 was required for suppression of PAD in pt4, while AMT2;4, but not AMT2;3, complemented growth of a yeast ammonium transporter mutant. In summary, arbuscule life span is influenced by PT4 and ATM2;3, and their relative importance varies with the nitrogen status of the plant. PMID:25841038

  10. Suppression of Arbuscule Degeneration in Medicago truncatula phosphate transporter4 Mutants is Dependent on the Ammonium Transporter 2 Family Protein AMT2;3.

    PubMed

    Breuillin-Sessoms, Florence; Floss, Daniela S; Gomez, S Karen; Pumplin, Nathan; Ding, Yi; Levesque-Tremblay, Veronique; Noar, Roslyn D; Daniels, Dierdra A; Bravo, Armando; Eaglesham, James B; Benedito, Vagner A; Udvardi, Michael K; Harrison, Maria J

    2015-04-01

    During arbuscular mycorrhizal (AM) symbiosis, the plant gains access to phosphate (Pi) and nitrogen delivered by its fungal symbiont. Transfer of mineral nutrients occurs at the interface between branched hyphae called arbuscules and root cortical cells. In Medicago truncatula, a Pi transporter, PT4, is required for symbiotic Pi transport, and in pt4, symbiotic Pi transport fails, arbuscules degenerate prematurely, and the symbiosis is not maintained. Premature arbuscule degeneration (PAD) is suppressed when pt4 mutants are nitrogen-deprived, possibly the result of compensation by PT8, a second AM-induced Pi transporter. However, PAD is also suppressed in nitrogen-starved pt4 pt8 double mutants, negating this hypothesis and furthermore indicating that in this condition, neither of these symbiotic Pi transporters is required for symbiosis. In M. truncatula, three AMT2 family ammonium transporters are induced during AM symbiosis. To test the hypothesis that suppression of PAD involves AMT2 transporters, we analyzed double and triple Pi and ammonium transporter mutants. ATM2;3 but not AMT2;4 was required for suppression of PAD in pt4, while AMT2;4, but not AMT2;3, complemented growth of a yeast ammonium transporter mutant. In summary, arbuscule life span is influenced by PT4 and ATM2;3, and their relative importance varies with the nitrogen status of the plant. PMID:25841038

  11. ‘Transient’ Genetic Suppression Facilitates Generation of Hexose Transporter Null Mutants in Leishmania mexicana

    PubMed Central

    Feng, Xiuhong; Rodriguez-Contreras, Dayana; Polley, Tamsen; Lye, Lon-Fye; Scott, David; Burchmore, Richard J.S.; Beverley, Stephen M.; Landfear, Scott M.

    2012-01-01

    Summary The genome of Leishmania mexicana encompasses a cluster of three glucose transporter genes designated LmxGT1, LmxGT2, and LmxGT3. Functional and genetic studies of a cluster null mutant (Δlmxgt1-3) have dissected the roles of these proteins in Leishmania metabolism and virulence. However, null mutants were recovered at very low frequency, and comparative genome hybridizations revealed that Δlmxgt1-3 mutants contained a linear extrachromosomal 40 kb amplification of a region on chromosome 29 not amplified in WT parasites. These data suggested a model where this 29–40k amplicon encoded a second site suppressor contributing to parasite survival in the absence of GT1-3 function. To test this, we quantified the frequency of recovery of knockouts in the presence of individual overexpressed ORFs covering the 29–40k amplicon. The data mapped the suppressor activity to PIFTC3, encoding a component of the intraflagellar transport pathway. We discuss possible models by which PIFTC3 might act to facilitate loss of GTs specifically. Surprisingly, by plasmid segregation we showed that continued PIFTC3 overexpression was not required for Δlmxgt1-3 viability. These studies provide the first evidence that genetic suppression can occur by providing critical biological functions transiently. This novel form of genetic suppression may extend to other genes, pathways and organisms. PMID:23170981

  12. Suppression by Trypanosoma brucei of anaphylaxis-mediated ion transport in the small intestine of rats.

    PubMed Central

    Gould, S S; Castro, G A

    1994-01-01

    The hypothesis that failure of hosts infected with Trypanosoma brucei to express type 1 hypersensitivity is related to this parasite's ability to down-regulate IgE production, and not to an innate lack of allergenicity of T. brucei antigens, was tested by studying anaphylaxis-induced changes in net epithelial ion transport in rats. Transport changes were quantified electrophysiologically in vitro, as a change in transmural short-circuit current when sensitized intestine was challenged with homologous antigen. Rats injected parenterally with trypanosome antigen elicited intestinal anaphylaxis in response to antigenic challenge, whereas the intestine of rats infected with T. brucei failed to respond. Infection with T. brucei also suppressed the anaphylactic response in rats sensitized to and challenged with ovalbumin and T. spiralis-derived antigens. In these cases suppression was related to the ability of T. brucei to block production of IgE, and not to the physiological failure of the epithelial response. However, in rats sensitized by infection with T. spiralis, neither the anaphylactic response nor IgE production were inhibited by T. brucei. Furthermore, intestinal mastocytosis normally associated with trichinosis was unaffected by the trypanosome infection. Results support the conclusion that the failure to express anaphylaxis in T. brucei-infected rats is due to the inhibition of IgE production and not to the lack of allergenicity of trypanosome antigens. PMID:8206518

  13. Hypotensive and vasorelaxant effects of sericin-derived oligopeptides in rats.

    PubMed

    Onsa-Ard, Amnart; Shimbhu, Dawan; Tocharus, Jiraporn; Sutheerawattananonda, Manote; Pantan, Rungusa; Tocharus, Chainarong

    2013-01-01

    Sericin-derived oligopeptides obtained from silk cocoons were investigated for the in vivo hypotensive effect and investigated for the underlying mechanism involved in vasodilation in isolated rat thoracic aorta. In normotensive anesthetized rats, oligopeptides induced an immediate and transient hypotensive activity. In rat aortic rings, oligopeptides induced a concentration-dependent vasorelaxation in vessels precontracted with both KCl and phenylephrine (PE) with endothelium-intact or endothelium-denuded rings. In endothelium-intact rings, pretreatment with N ω -Nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 µM), an inhibitor of the NO synthase (NOS) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 µM), a selective inhibitor of the guanylyl cyclase enzyme, significantly reduced the relaxant effect of oligopeptides. However, indomethacin, an inhibitor of the cyclooxygenase, had no effect on oligopeptides-induced relaxation. In addition, pretreatment with tetraethylammonium (TEA, 5 mM) reduced the maximal relaxant effect induced by oligopeptides. By contrast, relaxation was not affected by 4-aminopyridine (4-AP, 1 mM), glibenclamide (10 µM), or barium chloride (BaCl2, 1 mM). In depolarization Ca(2+)-free solution, oligopeptides inhibited calcium chloride- (CaCl2-) induced contraction in endothelium-denuded rings in a concentration-dependent manner. Nevertheless, oligopeptides attenuated transient contractions in Ca(2+)-free medium containing EGTA (1 mM) induced by 1 µM PE, but they were not affected by 20 mM caffeine. It is obvious that potent vasodilation effect of oligopeptides is mediated through both the endothelium and the vascular smooth muscle. PMID:24312733

  14. Suppression of Baryon Diffusion and Transport in a Baryon Rich Strongly Coupled Quark-Gluon Plasma

    NASA Astrophysics Data System (ADS)

    Rougemont, Romulo; Noronha, Jorge; Noronha-Hostler, Jacquelyn

    2015-11-01

    Five dimensional black hole solutions that describe the QCD crossover transition seen in (2 +1 ) -flavor lattice QCD calculations at zero and nonzero baryon densities are used to obtain predictions for the baryon susceptibility, baryon conductivity, baryon diffusion constant, and thermal conductivity of the strongly coupled quark-gluon plasma in the range of temperatures 130 MeV ≤T ≤300 MeV and baryon chemical potentials 0 ≤μB≤400 MeV . Diffusive transport is predicted to be suppressed in this region of the QCD phase diagram, which is consistent with the existence of a critical end point at larger baryon densities. We also calculate the fourth-order baryon susceptibility at zero baryon chemical potential and find quantitative agreement with recent lattice results. The baryon transport coefficients computed in this Letter can be readily implemented in state-of-the-art hydrodynamic codes used to investigate the dense QGP currently produced at RHIC's low energy beam scan.

  15. Suppression of Baryon Diffusion and Transport in a Baryon Rich Strongly Coupled Quark-Gluon Plasma.

    PubMed

    Rougemont, Romulo; Noronha, Jorge; Noronha-Hostler, Jacquelyn

    2015-11-13

    Five dimensional black hole solutions that describe the QCD crossover transition seen in (2+1)-flavor lattice QCD calculations at zero and nonzero baryon densities are used to obtain predictions for the baryon susceptibility, baryon conductivity, baryon diffusion constant, and thermal conductivity of the strongly coupled quark-gluon plasma in the range of temperatures 130  MeV≤T≤300  MeV and baryon chemical potentials 0≤μ(B)≤400  MeV. Diffusive transport is predicted to be suppressed in this region of the QCD phase diagram, which is consistent with the existence of a critical end point at larger baryon densities. We also calculate the fourth-order baryon susceptibility at zero baryon chemical potential and find quantitative agreement with recent lattice results. The baryon transport coefficients computed in this Letter can be readily implemented in state-of-the-art hydrodynamic codes used to investigate the dense QGP currently produced at RHIC's low energy beam scan. PMID:26613433

  16. Convective Transport Suppression in the Scrape-Off Layer Using Ion Cyclotron Resonance Heating on the ASDEX Upgrade Tokamak

    SciTech Connect

    Antar, G.; Assas, S.; Bobkov, V.; Noterdaeme, J.-M.; Wolfrum, E.; Herrmann, A.; Rohde, V.

    2010-10-15

    Turbulence properties in the scrape-off layer (SOL) in the presence of ion cyclotron frequency heating (ICRH) are compared to instances where it is absent. The discharges are all in a high-confinement mode (H-mode) regime. During ICRH, the SOL plasma density increases whereas turbulence large-scale and convective structures are shown to be suppressed. The probability distribution function is thus recorded to be closer to a Gaussian, and a net decrease in the low-frequency density fluctuations is reflected in the power spectra. Consequently, the level of turbulent fluctuations decreases significantly. Turbulence suppression is also reported during edge localized modes (ELMs) where both the ELMs-induced transport and duration are strongly affected. The increase of neutrals by gas puffing did not alter this behavior. We deduce that ICRH can be used as to suppress convective transport and reduce the ELM's amplitude.

  17. Oligopeptide-heavy metal interaction monitoring by hybrid gold nanoparticle based assay.

    PubMed

    Politi, Jane; Spadavecchia, Jolanda; Iodice, Mario; de Stefano, Luca

    2015-01-01

    Phytochelatins are small peptides that can be found in several organisms, which use these oligopeptides to handle heavy metal elements. Here, we report a method for monitoring interactions between lead(ii) ions in aqueous solutions and phytochelatin 6 oligopeptide bioconjugated onto pegylated gold nanorods (PEG-AuNrs). This study is the first step towards a high sensitive label free optical biosensor to quantify heavy metal pollution in water. PMID:25360445

  18. Evaluating the effects of charged oligopeptide motifs coupled with RGD on osteogenic differentiation of mesenchymal stem cells.

    PubMed

    Cao, Feng-Yi; Yin, Wei-Na; Fan, Jin-Xuan; Tao, Li; Qin, Si-Yong; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2015-04-01

    Mesenchymal stem cells, due to their multilineage differentiation potential, have emerged as a promising cell candidate for cell-based therapy. In recent years, biomaterials were artificially synthesized to control the differentiation of mesenchymal stem cells. In this study, a series of charged or neutral oligopeptide motifs coupled with RGD were synthesized and used for surface modification using quartz substrates as model. Cell behaviors on the modified surfaces with different charged oligopeptide motifs were studied. It was found that these different charged oligopeptide motifs coupled with RGD were biocompatible for cell proliferation and adhesion. Moreover, it was demonstrated that the positively charged oligopeptide motif could inhibit osteogenic differentiation, while the negatively charged and neutral oligopeptide motifs could enhance osteogenic differentiation in the presence of RGD. This work may bring us enlightenment that different charged oligopeptide motifs coupled with RGD may be used for biomaterial surface modification for different stem cell-based therapies. PMID:25748883

  19. Turbulence and transport suppression scaling with flow shear on the Large Plasma Device

    SciTech Connect

    Schaffner, D. A.; Carter, T. A.; Rossi, G. D.; Guice, D. S.; Maggs, J. E.; Vincena, S.; Friedman, B.

    2013-05-15

    Continuous control over azimuthal flow and shear in the edge of the Large Plasma Device (LAPD) [W. Gekelman et al., Rev. Sci. Instr. 62, 2875 (1991)] has been achieved using a biasable limiter. This flow control has allowed a careful study of the effect of flow shear on pressure-gradient-driven turbulence and particle transport in LAPD. The combination of externally controllable shear in a turbulent plasma along with the detailed spatial diagnostic capabilities on LAPD makes the experiment a useful testbed for validation of shear suppression models. Motivated by these models, power-law fits are made to the density and radial velocity fluctuation amplitudes, particle flux, density-potential crossphase, and radial correlation length. The data show a break in the trend of these quantities when the shearing rate (γ{sub s}=∂V{sub θ}/∂r) is comparable to the turbulent decorrelation rate (1/τ{sub ac}). No one model captures the trends in the all turbulent quantities for all values of the shearing rate, but some models successfully match the trend in either the weak (γ{sub s}τ{sub ac}<1) or strong (γ{sub s}τ{sub ac}>1) shear limits.

  20. Expression of the Oligopeptide Permease Operon of Moraxella catarrhalis Is Regulated by Temperature and Nutrient Availability.

    PubMed

    Jones, Megan M; Murphy, Timothy F

    2015-09-01

    Moraxella catarrhalis causes otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults. Together, these two conditions contribute to enormous morbidity and mortality worldwide. The oligopeptide permease (opp) ABC transport system is a nutritional virulence factor important for the utilization of peptides. The substrate binding protein OppA, which binds peptides for uptake, is a potential vaccine antigen, but little was known about the regulation of gene expression. The five opp genes oppB, oppC, oppD, oppF, and oppA are in the same open reading frame. Sequence analysis predicted two promoters, one located upstream of oppB and one within the intergenic region between oppF and oppA. We have characterized the gene cluster as an operon with two functional promoters and show that cold shock at 26°C for ≤ 0.5 h and the presence of a peptide substrate increase gene transcript levels. Additionally, the putative promoter upstream of oppA contributes to the transcription of oppA but is not influenced by the same environmental cues as the promoter upstream of oppB. We conclude that temperature and nutrient availability contribute to the regulation of the Opp system, which is an important nutritional virulence factor in M. catarrhalis. PMID:26099587

  1. Molecular interactions between dipeptides, drugs and the human intestinal H+ -oligopeptide cotransporter hPEPT1.

    PubMed

    Sala-Rabanal, Monica; Loo, Donald D F; Hirayama, Bruce A; Turk, Eric; Wright, Ernest M

    2006-07-01

    The human intestinal proton-coupled oligopeptide transporter hPEPT1 has been implicated in the absorption of pharmacologically active compounds. We have investigated the interactions between a comprehensive selection of drugs, and wild-type and variant hPEPT1s expressed in Xenopus oocytes, using radiotracer uptake and electrophysiological methods. The beta-lactam antibiotics ampicillin, amoxicillin, cephalexin and cefadroxil, the antineoplastics delta-aminolevulinic acid (delta-ALA) and bestatin, and the neuropeptide N-acetyl-Asp-Glu (NAAG), were transported, as judged by their ability to evoke inward currents. When the drugs were added in the presence of the typical substrate glycylsarcosine (Gly-Sar), the inward currents were equal or less than that induced by Gly-Sar alone. This suggests that the drugs are transported at a lower turnover rate than Gly-Sar, but may also point towards complex interactions between dipeptides, drugs and the transporter. Gly-Sar and the drugs also modified the kinetics of hPEPT1 presteady-state charge movement, by causing a reduction in maximum charge (Qmax) and a shift of the midpoint voltage (V0.5) to more negative potentials. Our results indicate that the substrate selectivity of hPEPT1 is: Gly-Sar > NAAG, delta-ALA, bestatin > cefadroxil, cephalexin > ampicillin, amoxicillin. Based on steady-state and presteady-state analysis of Gly-Sar and cefadroxil transport, we proposed an extension of the 6-state kinetic model for hPEPT1 function that globally accounts for the observed presteady-state and steady-state kinetics of neutral dipeptide and drug transport. Our model suggests that, under saturating conditions, the rate-limiting step of the hPEPT1 transport cycle is the reorientation of the empty carrier within the membrane. Variations in rates of drug cotransport are predicted to be due to differences in affinity and turnover rate. Oral availability of drugs may be reduced in the presence of physiological concentrations of dietary

  2. Distribution and biological role of the oligopeptide-binding protein (OppA) in Xanthomonas species.

    PubMed

    Oshiro, Elisa E; Tavares, Milene B; Suzuki, Celso F; Pimenta, Daniel C; Angeli, Claudia B; de Oliveira, Julio C F; Ferro, Maria I T; Ferreira, Luis C S; Ferreira, Rita C C

    2010-04-01

    In this study we investigated the prevalence of the oppA gene, encoding the oligopeptide binding protein (OppA) of the major bacterial oligopeptide uptake system (Opp), in different species of the genus Xanthomonas. The oppA gene was detected in two Xanthomonas axonopodis strains among eight tested Xanthomonas species. The generation of an isogenic oppA-knockout derivative of the Xac 306 strain, showed that the OppA protein neither plays a relevant role in oligopeptide uptake nor contributes to the infectivity and multiplication of the bacterial strain in leaves of sweet orange (Citrus sinensis) and Rangpur lime (Citrus limonia). Taken together these results suggest that the oppA gene has a recent evolutionary history in the genus and does not contribute in the physiology or pathogenesis of X. axonopodis. PMID:21637492

  3. Putative antiparasite defensive system involving ribosomal and nonribosomal oligopeptides in cyanobacteria of the genus Planktothrix.

    PubMed

    Rohrlack, Thomas; Christiansen, Guntram; Kurmayer, Rainer

    2013-04-01

    Parasitic chytrid fungi can inflict significant mortality on cyanobacteria but frequently fail to keep cyanobacterial dominance and bloom formation in check. Our study tested whether oligopeptide production, a common feature in many cyanobacteria, can be a defensive mechanism against chytrid parasitism. The study employed the cyanobacterial strain Planktothrix NIVA-CYA126/8 and its mutants with knockout mutations for microcystins, anabaenopeptins, and microviridins, major oligopeptide classes to be found in NIVA-CYA126/8. Four chytrid strains were used as parasite models. They are obligate parasites of Planktothrix and are unable to exploit alternative food sources. All chytrid strains were less virulent to the NIVA-CYA126/8 wild type than to at least one of its oligopeptide knockout mutants. One chytrid strain even failed to infect the wild type, while exhibiting considerable virulence to all mutants. It is therefore evident that producing microcystins, microviridins, and/or anabaenopeptins can reduce the virulence of chytrids to Planktothrix, thereby increasing the host's chance of survival. Microcystins and anabaenopeptins are nonribosomal oligopeptides, while microviridins are produced ribosomally, suggesting that Planktothrix resists chytrids by relying on metabolites that are produced via distinct biosynthetic pathways. Chytrids, on the other hand, can adapt to the oligopeptides produced by Planktothrix in different ways. This setting most likely results in an evolutionary arms race, which would probably lead to Planktothrix and chytrid population structures that closely resemble those actually found in nature. In summary, the findings of the present study suggest oligopeptide production in Planktothrix to be part of a defensive mechanism against chytrid parasitism. PMID:23396340

  4. Proline rich-oligopeptides: diverse mechanisms for antihypertensive action.

    PubMed

    Morais, Katia L P; Ianzer, Danielle; Miranda, José Rodolfo R; Melo, Robson L; Guerreiro, Juliano R; Santos, Robson A S; Ulrich, Henning; Lameu, Claudiana

    2013-10-01

    Bradykinin-potentiating peptides from Bothrops jararaca (Bj) discovered in the early 1960s, were the first natural inhibitors of the angiotensin-converting enzyme (ACE). These peptides belong to a large family of snake venom proline-rich oligopeptides (PROs). One of these peptides, Bj-PRO-9a, was essential for defining ACE as effective drug target and development of captopril, an active site-directed inhibitor of ACE used worldwide for the treatment of human arterial hypertension. Recent experimental evidences demonstrated that cardiovascular effects exerted by different Bj-PROs are due to distinct mechanisms besides of ACE inhibition. In the present work, we have investigated the cardiovascular actions of four Bj-PROs, namely Bj-PRO-9a, -11e, -12b and -13a. Bj-PRO-9a acts upon ACE and BK activities to promote blood pressure reduction. Although the others Bj-PROs are also able to inhibit the ACE activity and to potentiate the BK effects, our results indicate that antihypertensive effect evoked by them involve new mechanisms. Bj-PRO-11e and Bj-PRO-12b involves induction of [Ca(2+)]i transients by so far unknown receptor proteins. Moreover, we have suggested argininosuccinate synthetase and M3 muscarinic receptor as targets for cardiovascular effects elicited by Bj-PRO-13a. In summary, the herein reported results provide evidence that Bj-PRO-mediated effects are not restricted to ACE inhibition or potentiation of BK-induced effects and suggest different actions for each peptide for promoting arterial pressure reduction. The present study reveals the complexity of the effects exerted by Bj-PROs for cardiovascular control, opening avenues for the better understanding of blood pressure regulation and for the development of novel therapeutic approaches. PMID:23933300

  5. Pretranslational Suppression of an Insulin-Responsive Glucose Transporter in Rats with Diabetes Mellitus

    NASA Astrophysics Data System (ADS)

    Garvey, W. Timothy; Huecksteadt, Thomas P.; Birnbaum, Morris J.

    1989-07-01

    A prominent feature of diabetes mellitus is the inability of insulin to appropriately increase the transport of glucose into target tissues. The contributions of different glucose transport proteins to insulin resistance in rats with streptozotocin-induced diabetes was evaluated. A glucose transporter messenger RNA and its cognate protein that are exclusively expressed in muscle and adipose tissue were specifically depleted in diabetic animals, and these effects were reversed after insulin therapy; a different glucose transporter and its messenger RNA that exhibit a less restricted tissue distribution were not specifically modulated in this way. Depletion of the muscle- and adipose-specific glucose transporter species correlates with and may account for the major portion of cellular insulin resistance in diabetes in these animals.

  6. Solid-Phase Organic Synthesis and Combinatorial Chemistry: A Laboratory Preparation of Oligopeptides

    NASA Astrophysics Data System (ADS)

    Truran, George A.; Aiken, Karelle S.; Fleming, Thomas R.; Webb, Peter J.; Hodge Markgraf, J.

    2002-01-01

    The principles and practice of solid-phase organic synthesis and combinatorial chemistry are utilized in a laboratory preparation of oligopeptides. A parallel synthesis scheme is used to generate a series of tripeptides. A divergent synthesis scheme is used to prepare two pentapeptides, one of which is leucine enkephalin, a neurotransmitter known to be an analgesic agent.

  7. Influence of fermentation level and geographical origin on cocoa bean oligopeptide pattern.

    PubMed

    Caligiani, Augusta; Marseglia, Angela; Prandi, Barbara; Palla, Gerardo; Sforza, Stefano

    2016-11-15

    Peptides and amino acids generated during cocoa bean fermentation are the most important precursors for the development of cocoa aroma, however cocoa oligopeptide fraction is under-investigated. In this study, we perform a deep investigation of the presence of oligopeptides in unfermented, under fermented, and well-fermented cocoa beans from all of the main producing countries, with the aim to obtain a better definition of cocoa quality and a deeper comprehension of biochemical changes occurring during fermentation. Oligopeptides were determined by UPLC/ESI-MS and 35 low-molecular weight peptides were identified and subjected to semi-quantitative analysis. Results showed that fermented cocoas can be differentiated from unfermented cocoas by their possession of a higher total amount of oligopeptides and a lower ratio of vicilin to 21kDa cocoa seed albumin peptides. A variability in the peptide pattern was observed also among well-fermented cocoa samples of different geographical origin, suggesting diversified proteolytic activities. PMID:27283652

  8. Interleukin-1β Suppresses the Transporter Genes Ank and Ent1 Expression in Stromal Progenitor Cells Retaining Mineralization.

    PubMed

    Ezura, Yoichi; Lin, Xin; Hatta, Arina; Izu, Yayoi; Noda, Masaki

    2016-08-01

    Heterotopic ossification (HO) in various tissues evokes clinical problems. Inflammatory responses of the stromal progenitor cells may be involved in its etiology. Previous report indicated that pro-inflammatory cytokines including IL-1β enhanced the in vitro calcification of human mesenchymal stem cells (MSCs), by suppressing the expression of ectonucleotide pyrophosphatase/phosphodiesterase-1 gene (ENPP1). However, possible contribution of other related factors had not been investigated. Here, we investigated the expression of regulators of extracellular pyrophosphate and nucleosides including Enpp1, Nt5e, Ank, Enptds, and Ent1, examining various connective tissue stromal progenitor cells, including bone marrow stromal cells and synovium derived cells from mouse, or bone marrow MSCs from human. Consistent with previous studies, we observed characteristic suppression of the osteoblastic marker genes by IL-1β during the osteogenic culture for 20 days. In addition, we observed a reduced expression of the important transporter genes, Ank and Ent1, whereas the alteration in Enpp1 and Nt5e levels was not always consistent among the cell types. Our results suggest that IL-1β suppresses not only the osteoblastic but also the negative regulators of soft-tissue calcification, including Ank and Ent1 in stromal progenitor cells, which may contribute to the mechanisms of HO in various disorders. PMID:27086348

  9. Suppressed intrinsic catalytic activity of GLUT1 glucose transporters in insulin-sensitive 3T3-L1 adipocytes

    SciTech Connect

    Harrison, S.A.; Buxton, J.M.; Czech, M.P. )

    1991-09-01

    Previous studies indicated that the erythroid-type (GLUT1) glucose transporter isoform contributes to basal but not insulin-stimulated hexose transport in mouse 3T3-L1 adipocytes. In the present studies it was found that basal hexose uptake in 3T3-L1 adipocytes was about 50% lower than that in 3T3-L1 or CHO-K1 fibroblasts. Intrinsic catalytic activities of GLUT1 transporters in CHO-K1 and 3T3-L1 cells were compared by normalizing these hexose transport rates to GLUT1 content on the cell surface, as measured by two independent methods. Cell surface GLUT1 levels in 3T3-L1 fibroblasts and adipocytes were about 10- and 25-fold higher, respectively, than in CHO-K1 fibroblasts, as assessed with an anti-GLUT1 exofacial domain antiserum, delta. The large excess of cell surface GLUT1 transporters in 3T3-L1 adipocytes relative to CHO-K1 fibroblasts was confirmed by GLUT1 protein immunoblot analysis and by photoaffinity labeling (with 3-({sup 125}I)iodo-4-azidophenethylamido-7-O-succinyldeacetylforskolin) of glucose transporters in isolated plasma membranes. Thus, GLUT1 intrinsic activity is markedly reduced in 3T3-L1 fibroblasts compared with the CHO-K1 fibroblasts, and further reduction occurs upon differentiation to adipocytes. The authors conclude that a mechanism that markedly suppresses basal hexose transport catalyzed by GLUT1 is a major contributor to the dramatic insulin sensitivity of glucose uptake in 3T3-L1 adipocytes.

  10. Hesperidin Suppresses Melanosome Transport by Blocking the Interaction of Rab27A-Melanophilin

    PubMed Central

    Kim, Bora; Lee, Jee-Young; Lee, Ha-Yeon; Nam, Ky-Youb; Park, JongIl; Lee, Su Min; Kim, Jin Eun; Lee, Joo Dong; Hwang, Jae Sung

    2013-01-01

    We investigated the inhibitory effects of hesperidin on melanogenesis. To find melanosome transport inhibitor from natural products, we collected the structural information of natural products from Korea Food and Drug Administration (KFDA) and performed pharmacophore-based in silico screening for Rab27A and melanophilin (MLPH). Hesperidin did not inhibit melanin production in B16F10 murine melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH), and also did not affect the catalytic activity of tyrosinase. But, hesperidin inhibited melanosome transport in melanocyte and showed skin lightening effect in pigmented reconstructed epidermis model. Therefore, we suggest that hesperidin is a useful inhibitor of melanosome transport and it might be applied to whitening agent. PMID:24244821

  11. Suppression of glymphatic fluid transport in a mouse model of Alzheimer's disease.

    PubMed

    Peng, Weiguo; Achariyar, Thiyagarajan M; Li, Baoman; Liao, Yonghong; Mestre, Humberto; Hitomi, Emi; Regan, Sean; Kasper, Tristan; Peng, Sisi; Ding, Fengfei; Benveniste, Helene; Nedergaard, Maiken; Deane, Rashid

    2016-09-01

    Glymphatic transport, defined as cerebrospinal fluid (CSF) peri-arterial inflow into brain, and interstitial fluid (ISF) clearance, is reduced in the aging brain. However, it is unclear whether glymphatic transport affects the distribution of soluble Aβ in Alzheimer's disease (AD). In wild type mice, we show that Aβ40 (fluorescently labeled Aβ40 or unlabeled Aβ40), was distributed from CSF to brain, via the peri-arterial space, and associated with neurons. In contrast, Aβ42 was mostly restricted to the peri-arterial space due mainly to its greater propensity to oligomerize when compared to Aβ40. Interestingly, pretreatment with Aβ40 in the CSF, but not Aβ42, reduced CSF transport into brain. In APP/PS1 mice, a model of AD, with and without extensive amyloid-β deposits, glymphatic transport was reduced, due to the accumulation of toxic Aβ species, such as soluble oligomers. CSF-derived Aβ40 co-localizes with existing endogenous vascular and parenchymal amyloid-β plaques, and thus, may contribute to the progression of both cerebral amyloid angiopathy and parenchymal Aβ accumulation. Importantly, glymphatic failure preceded significant amyloid-β deposits, and thus, may be an early biomarker of AD. By extension, restoring glymphatic inflow and ISF clearance are potential therapeutic targets to slow the onset and progression of AD. PMID:27234656

  12. Inhibition of monocarboxylate transporter 1 suppresses the proliferation of glioblastoma stem cells.

    PubMed

    Takada, Tetsuya; Takata, Kazuyuki; Ashihara, Eishi

    2016-09-01

    Recent evidence suggests that a minor subset of cancer cells, termed cancer stem cells (CSCs), have self-renewal and tumorigenic potential. Therefore, the characterization of CSCs is important for developing therapeutic strategies against cancer. Cancer cells rely on anaerobic glycolysis to produce ATP even under normoxic conditions, resulting in the generation of excess acidic substances. Cancer cells maintain a weakly alkaline intracellular pH to support functions. Glioblastoma is an aggressive malignancy with a poor 5-year survival rate. Based on the hypothesis that ion transport-related molecules regulate the viability and function of CSCs, we investigated the expression of ion transport-related molecules in glioblastoma CSCs (GSCs). Quantitative RT-PCR analysis showed that monocarboxylate transporter1 (MCT1) were upregulated in GSCs, and inhibition of MCT1 decreased the viability of GSCs compared with that of non-GSCs. Our findings indicate that MCT1 is involved in the maintenance of GSCs and is a promising therapeutic target for glioblastoma. PMID:26902636

  13. Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth.

    PubMed

    McIntyre, Alan; Hulikova, Alzbeta; Ledaki, Ioanna; Snell, Cameron; Singleton, Dean; Steers, Graham; Seden, Peter; Jones, Dylan; Bridges, Esther; Wigfield, Simon; Li, Ji-Liang; Russell, Angela; Swietach, Pawel; Harris, Adrian L

    2016-07-01

    Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extracellularly by CA9 could exacerbate the intracellular acidity produced by hypoxic conditions, perhaps compromising cell growth and viability as a result. In 8 of 10 cancer cell lines, we found that hypoxia induced the expression of at least one bicarbonate transporter. The most robust and frequent inductions were of the sodium-driven bicarbonate transporters SLC4A4 and SLC4A9, which rely upon both HIF1α and HIF2α activity for their expression. In cancer cell spheroids, SLC4A4 or SLC4A9 disruption by either genetic or pharmaceutical approaches acidified intracellular pH and reduced cell growth. Furthermore, treatment of spheroids with S0859, a small-molecule inhibitor of sodium-driven bicarbonate transporters, increased apoptosis in the cell lines tested. Finally, RNAi-mediated attenuation of SLC4A9 increased apoptosis in MDA-MB-231 breast cancer spheroids and dramatically reduced growth of MDA-MB-231 breast tumors or U87 gliomas in murine xenografts. Our findings suggest that disrupting pH homeostasis by blocking bicarbonate import might broadly relieve the common resistance of hypoxic tumors to anticancer therapy. Cancer Res; 76(13); 3744-55. ©2016 AACR. PMID:27197160

  14. Inclusion of Cu nano-cluster 1D arrays inside a C3-symmetric artificial oligopeptide via co-assembly

    NASA Astrophysics Data System (ADS)

    Gong, Ruiying; Li, Fei; Yang, Chunpeng; Wan, Xiaobo

    2015-12-01

    A peptide sequence N3-GVGV-OMe (G: glycine; V: valine) was attached to a benzene 1,3,5-tricarboxamide (BTA) derivative via ``click chemistry'' to afford a C3-symmetric artificial oligopeptide. The key feature of this oligopeptide is that the binding sites (triazole groups formed by click reaction) are located at the center, while the three oligopeptide arms with a strong tendency to assemble are located around it, which provides inner space to accommodate nanoparticles via self-assembly. The inclusion of Cu nanoclusters and the formation of one-dimensional (1D) arrays inside the nanofibers of the C3-symmetric artificial oligopeptide assembly were observed, which is quite different from the commonly observed nanoparticle growth on the surface of the pre-assembled oligopeptide nanofibers via the coordination sites located outside. Our finding provides an instructive concept for the design of other stable organic-inorganic hybrid 1D arrays with the inorganic nanoparticles inside.A peptide sequence N3-GVGV-OMe (G: glycine; V: valine) was attached to a benzene 1,3,5-tricarboxamide (BTA) derivative via ``click chemistry'' to afford a C3-symmetric artificial oligopeptide. The key feature of this oligopeptide is that the binding sites (triazole groups formed by click reaction) are located at the center, while the three oligopeptide arms with a strong tendency to assemble are located around it, which provides inner space to accommodate nanoparticles via self-assembly. The inclusion of Cu nanoclusters and the formation of one-dimensional (1D) arrays inside the nanofibers of the C3-symmetric artificial oligopeptide assembly were observed, which is quite different from the commonly observed nanoparticle growth on the surface of the pre-assembled oligopeptide nanofibers via the coordination sites located outside. Our finding provides an instructive concept for the design of other stable organic-inorganic hybrid 1D arrays with the inorganic nanoparticles inside. Electronic

  15. Synthetic oligopeptide substrates: their diagnostic application in blood coagulation, fibrinolysis, and other pathologic states

    SciTech Connect

    Huseby, R.M.; Smith, R.E.

    1980-01-01

    This review article with 522 references, focuses on the use of synthetic oligopepide substrates to measure the activity of proteoytic enzymes in human physiology and pathology. A classification of proteinases based on their mechanism of action is presented. The application of these synthetic oligopeptide substrates to understand the disorders of the blood coagulation and fibrinolytic system is reviewed. Intracellular functioning proteinases were also assessed in relation to certain pathologies where their abnormal activity is recognized.

  16. Mineral-Enhanced Hydrothermal Oligopeptide Formation at the Second Time Scale

    NASA Astrophysics Data System (ADS)

    Kawamura, Kunio; Takeya, Hitoshi; Kushibe, Takao; Koizumi, Yuka

    2011-06-01

    Accumulation of biopolymers should have been an essential step for the emergence of life on primitive Earth. However, experimental simulations for submarine hydrothermal vent systems in which high-temperature water spouts through minerals within a short time scale have not been attempted. Here, we show that enhancement of hydrothermal oligopeptide elongation by naturally occurring minerals was successfully verified for the first time by using a mineral-mediated hydrothermal flow reactor system (MMHF). MMHF consists of a narrow tubular reactor packed with mineral particles, and the enhancement or inhibitory activities of 10 types of naturally occurring minerals were successfully evaluated for an elongation reaction from (Ala)4 to (Ala)5 and higher oligopeptides in the absence of condensation reagents. It was unexpected that calcite and dolomite facilitated the elongation from (Ala)4 to (Ala)5 and higher oligopeptides with 28% yield at pH 7, while tourmaline, galena, apatite, mica, sphalerite, quartz, chalcopyrite, and pyrite did not show enhancement activities. These facts suggest the importance of carbonate minerals for the accumulation of peptide in primitive Earth environments.

  17. Mineral-enhanced hydrothermal oligopeptide formation at the second time scale.

    PubMed

    Kawamura, Kunio; Takeya, Hitoshi; Kushibe, Takao; Koizumi, Yuka

    2011-06-01

    Accumulation of biopolymers should have been an essential step for the emergence of life on primitive Earth. However, experimental simulations for submarine hydrothermal vent systems in which high-temperature water spouts through minerals within a short time scale have not been attempted. Here, we show that enhancement of hydrothermal oligopeptide elongation by naturally occurring minerals was successfully verified for the first time by using a mineral-mediated hydrothermal flow reactor system (MMHF). MMHF consists of a narrow tubular reactor packed with mineral particles, and the enhancement or inhibitory activities of 10 types of naturally occurring minerals were successfully evaluated for an elongation reaction from (Ala)(4) to (Ala)(5) and higher oligopeptides in the absence of condensation reagents. It was unexpected that calcite and dolomite facilitated the elongation from (Ala)(4) to (Ala)(5) and higher oligopeptides with 28% yield at pH 7, while tourmaline, galena, apatite, mica, sphalerite, quartz, chalcopyrite, and pyrite did not show enhancement activities. These facts suggest the importance of carbonate minerals for the accumulation of peptide in primitive Earth environments. PMID:21671764

  18. Controlled trial of oligopeptide versus amino acid diet in treatment of active Crohn's disease.

    PubMed Central

    Mansfield, J C; Giaffer, M H; Holdsworth, C D

    1995-01-01

    Elemental diets are effective in inducing remission in active Crohn's disease, but how they exert this therapeutic effect is unclear. In a previous study a whole protein containing diet proved less effective than one in which food antigens were excluded, suggesting that exclusion of food antigens from the gut was a possible mechanism. This study was designed to test whether an oligopeptide diet of hydrolysed proteins was as effective as an amino acid based diet. These diets were equally antigen free but with different nitrogen sources. Forty four patients with active Crohn's disease were randomised in a controlled trial of amino acid versus oligopeptide diet. The feeds were given by nasogastric tube in equicaloric quantities and were the sole form of nutrition. Treatment was continued for four weeks although failure to improve by day 10 resulted in withdrawal. Quantitative leucocyte scintigraphy was used to investigate the effect of diet treatment on gut inflammation. Clinical and nutritional responses to treatment were also measured. Sixteen patients entered remission (including withdrawal of corticosteroids), six patients could not tolerate the nasogastric tube, and 22 patients failed to respond. The two diets were equally effective. Patients who responded had a rapid drop in clinical index of disease activity and a major reduction in the bowel uptake of leucocytes on scintigraphy. The oligopeptide and amino acid based enteral feeds were equally effective at inducing remission in active Crohn's disease. With both diets clinical improvement was accompanied by a reduction in intestinal inflammation. Images Figure 3 PMID:7890238

  19. Molecular characterization of group A streptococcal (GAS) oligopeptide permease (opp) and its effect on cysteine protease production.

    PubMed

    Podbielski, A; Pohl, B; Woischnik, M; Körner, C; Schmidt, K H; Rozdzinski, E; Leonard, B A

    1996-09-01

    Bacterial oligopeptide permeases are membrane-associated complexes of five proteins belonging to the ABC-transporter family, which have been found to be involved in obtaining nutrients, cell-wall metabolism, competence, and adherence to host cells. A lambda library of the strain CS101 group A streptococcal (GAS) genome was used to sequence 10,192 bp containing the five genes oppA to oppF of the GAS opp operon. The deduced amino acid sequences exhibited 50-84% homology to pneumococcal AmiA to AmiF sequences. The operon organization of the five genes was confirmed by transcriptional analysis and an additional shorter oppA transcript was detected. Insertional inactivation was used to create serotype M49 strains which did not express either the oppA gene or the ATPase genes, oppD and oppF. The mutation in oppA confirmed that the additional shorter oppA transcript originated from the opp operon and was probably due to an intra-operon transcription terminator site located downstream of oppA. While growth kinetics, binding of serum proteins, and attachment to eukaryotic cells were unaffected, the oppD/F mutants showed reduced production of the cysteine protease, SpeB, and a change in the pattern of secreted proteins. Thus, the GAS opp operon appears to contribute to both protease production and export/processing of secreted proteins. PMID:8885277

  20. Hypouricemic effects of novel concentrative nucleoside transporter 2 inhibitors through suppressing intestinal absorption of purine nucleosides.

    PubMed

    Hiratochi, Masahiro; Tatani, Kazuya; Shimizu, Kazuo; Kuramochi, Yu; Kikuchi, Norihiko; Kamada, Noboru; Itoh, Fumiaki; Isaji, Masayuki

    2012-09-01

    We have developed concentrative nucleoside transporter 2 (CNT2) inhibitors as a novel pharmacological approach for improving hyperuricemia by inhibiting intestinal absorption of purines. Dietary purine nucleosides are absorbed in the small intestines by CNTs expressed in the apical membrane. In humans, the absorbed purine nucleosides are rapidly degraded to their final end product, uric acid, by xanthine oxidase. Based on the expression profile of human CNTs in digestive tract tissues, we established a working hypothesis that mainly CNT2 contributes to the intestinal absorption of purine nucleosides. In order to confirm this possibility, we developed CNT2 inhibitors and found that (2R,3R,4S,5R)-2-(6-amino-8-{[3'-(3-aminopropoxy)-biphenyl-4-ylmethyl]-amino}-9H-purin-9-yl)-5-hydroxymethyl-tetrahydrofuran-3,4-diol (KGO-2142) and 1-[3-(5-{[1-((2R,3R,4S,5R)-3,4-dihydroxy-5-hydroxymethyl-tetrahydrofuran-2-yl)-1H-benzimidazol-2-ylamino]-methyl}-2-ethoxyphenoxy)-propyl]-piperidine-4-carboxylic acid amide (KGO-2173) were inhibitory. These CNT2 inhibitors had potent inhibitory activity against inosine uptake via human CNT2, but they did not potently interfere with nucleoside uptake via human CNT1, CNT3 or equilibrative nucleoside transporters (ENTs) in vitro. After oral administration of KGO-2173 along with [(14)C]-inosine, KGO-2173 significantly decreased the urinary excretion of radioactivity at 6 and 24h in rats. Since dietary purine nucleosides are not utilized in the body and are excreted into the urine rapidly, this decrease in radioactivity in the urine represented the inhibitory activity of KGO-2173 toward the absorption of [(14)C]-inosine in the small intestines. KGO-2142 almost completely inhibited dietary RNA-induced hyperuricemia and the increase in urinary excretion of uric acid in cebus monkeys. These novel CNT2 inhibitors, KGO-2142 and KGO-2173, could be useful therapeutic options for the treatment of hyperuricemia. PMID:22709993

  1. Charge transport model in solid-state avalanche amorphous selenium and defect suppression design

    NASA Astrophysics Data System (ADS)

    Scheuermann, James R.; Miranda, Yesenia; Liu, Hongyu; Zhao, Wei

    2016-01-01

    Avalanche amorphous selenium (a-Se) in a layer of High Gain Avalanche Rushing Photoconductor (HARP) is being investigated for its use in large area medical imagers. Avalanche multiplication of photogenerated charge requires electric fields greater than 70 V μm-1. For a-Se to withstand this high electric field, blocking layers are used to prevent the injection of charge carriers from the electrodes. Blocking layers must have a high injection barrier and deep trapping states to reduce the electric field at the interface. In the presence of a defect in the blocking layer, a distributed resistive layer (DRL) must be included into the structure to build up space charge and reduce the electric field in a-Se and the defect. A numerical charge transport model has been developed to optimize the properties of blocking layers used in various HARP structures. The model shows the incorporation of a DRL functionality into the p-layer can reduce dark current at a point defect by two orders of magnitude by reducing the field in a-Se to the avalanche threshold. Hole mobility in a DRL of ˜10-8 cm2 V-1 s-1 at 100 V μm-1 as demonstrated by the model can be achieved experimentally by varying the hole mobility of p-type organic or inorganic semiconductors through doping, e.g., using Poly(9-vinylcarbozole) doped with 1%-3% (by weight) of poly(3-hexylthiopene).

  2. Inhibition of Large Neutral Amino Acid Transporters Suppresses Kynurenic Acid Production Via Inhibition of Kynurenine Uptake in Rodent Brain.

    PubMed

    Sekine, Airi; Kuroki, Yusuke; Urata, Tomomi; Mori, Noriyuki; Fukuwatari, Tsutomu

    2016-09-01

    The tryptophan metabolite, kynurenic acid (KYNA), is a preferential antagonist of the α7 nicotinic acetylcholine receptor and N-methyl-D-aspartic acid receptor at endogenous brain concentrations. Recent studies have suggested that increases of brain KYNA levels are involved in psychiatric disorders such as schizophrenia and depression, and regulation of KYNA production has become a new target for treatment of these diseases. Kynurenine (KYN), the immediate precursor of KYNA, is transported into astrocytes via large neutral amino acid transporters (LATs). In the present study, the effect of LATs regulation on KYN uptake and KYNA production was investigated in vitro and in vivo using an LATs inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). In the in vitro study, cortical slices of rat brain were incubated with a physiological concentration of KYN and 3 µmol/L-3 mmol/L BCH. BCH inhibited KYNA production and KYN uptake in a dose-dependent manner, and their IC50 values were 90.7 and 97.4 µmol/L, respectively. In the in vivo study, mice were administered KYN (50 mg/kg BW) orally and BCH (200 mg/kg BW) intravenously. Administration of KYN increased brain KYN and KYNA levels compared with the mice treated with vehicle, whereas additional administration of BCH suppressed KYN-induced elevations in KYN and KYNA levels to 50 and 70 % in the brain. These results suggest that inhibition of LATs prevented the increase of KYNA production via blockade of KYN uptake in the brain in vitro and in vivo. LATs can be a target to modulate brain function by regulation of KYNA production in the brain. PMID:27161376

  3. Knockdown of the sodium-dependent phosphate co-transporter 2b (NPT2b) suppresses lung tumorigenesis.

    PubMed

    Hong, Seong-Ho; Minai-Tehrani, Arash; Chang, Seung-Hee; Jiang, Hu-Lin; Lee, Somin; Lee, Ah-Young; Seo, Hwi Won; Chae, Chanhee; Beck, George R; Cho, Myung-Haing

    2013-01-01

    The sodium-dependent phosphate co-transporter 2b (NPT2b) plays an important role in maintaining phosphate homeostasis. In previous studies, we have shown that high dietary inorganic phosphate (Pi) consumption in mice stimulated lung tumorigenesis and increased NPT2b expression. NPT2b has also been found to be highly expressed in human lung cancer tissues. The association of high expression of NPT2b in the lung with poor prognosis in oncogenic lung diseases prompted us to test whether knockdown of NPT2b may regulate lung cancer growth. To address this issue, aerosols that contained small interfering RNA (siRNA) directed against NPT2b (siNPT2b) were delivered into the lungs of K-ras (LA1) mice, which constitute a murine model reflecting human lung cancer. Our results clearly showed that repeated aerosol delivery of siNPT2b successfully suppressed lung cancer growth and decreased cancer cell proliferation and angiogenesis, while facilitating apoptosis. These results strongly suggest that NPT2b plays a role lung tumorigenesis and represents a novel target for lung cancer therapy. PMID:24194864

  4. Suppression pattern of neutral pions at high transverse momentum in Au + Au collisions at sqrt[sNN]=200 GeV and constraints on medium transport coefficients.

    PubMed

    Adare, A; Afanasiev, S; Aidala, C; Ajitanand, N N; Akiba, Y; Al-Bataineh, H; Alexander, J; Al-Jamel, A; Aoki, K; Aphecetche, L; Armendariz, R; Aronson, S H; Asai, J; Atomssa, E T; Averbeck, R; Awes, T C; Azmoun, B; Babintsev, V; Baksay, G; Baksay, L; Baldisseri, A; Barish, K N; Barnes, P D; Bassalleck, B; Bathe, S; Batsouli, S; Baublis, V; Bauer, F; Bazilevsky, A; Belikov, S; Bennett, R; Berdnikov, Y; Bickley, A A; Bjorndal, M T; Boissevain, J G; Borel, H; Boyle, K; Brooks, M L; Brown, D S; Bucher, D; Buesching, H; Bumazhnov, V; Bunce, G; Burward-Hoy, J M; Butsyk, S; Campbell, S; Chai, J-S; Chang, B S; Charvet, J-L; Chernichenko, S; Chiba, J; Chi, C Y; Chiu, M; Choi, I J; Chujo, T; Chung, P; Churyn, A; Cianciolo, V; Cleven, C R; Cobigo, Y; Cole, B A; Comets, M P; Constantin, P; Csanád, M; Csörgo, T; Dahms, T; Das, K; David, G; Deaton, M B; Dehmelt, K; Delagrange, H; Denisov, A; d'Enterria, D; Deshpande, A; Desmond, E J; Dietzsch, O; Dion, A; Donadelli, M; Drachenberg, J L; Drapier, O; Drees, A; Dubey, A K; Durum, A; Dzhordzhadze, V; Efremenko, Y V; Egdemir, J; Ellinghaus, F; Emam, W S; Enokizono, A; En'yo, H; Espagnon, B; Esumi, S; Eyser, K O; Fields, D E; Finger, M; Finger, M; Fleuret, F; Fokin, S L; Forestier, B; Fraenkel, Z; Frantz, J E; Franz, A; Frawley, A D; Fujiwara, K; Fukao, Y; Fung, S-Y; Fusayasu, T; Gadrat, S; Garishvili, I; Gastineau, F; Germain, M; Glenn, A; Gong, H; Gonin, M; Gosset, J; Goto, Y; de Cassagnac, R Granier; Grau, N; Greene, S V; Perdekamp, M Grosse; Gunji, T; Gustafsson, H-A; Hachiya, T; Henni, A Hadj; Haegemann, C; Haggerty, J S; Hagiwara, M N; Hamagaki, H; Han, R; Harada, H; Hartouni, E P; Haruna, K; Harvey, M; Haslum, E; Hasuko, K; Hayano, R; Heffner, M; Hemmick, T K; Hester, T; Heuser, J M; He, X; Hiejima, H; Hill, J C; Hobbs, R; Hohlmann, M; Holmes, M; Holzmann, W; Homma, K; Hong, B; Horaguchi, T; Hornback, D; Hur, M G; Ichihara, T; Imai, K; Imrek, J; Inaba, M; Inoue, Y; Isenhower, D; Isenhower, L; Ishihara, M; Isobe, T; Issah, M; Isupov, A; Jacak, B V; Jia, J; Jin, J; Jinnouchi, O; Johnson, B M; Joo, K S; Jouan, D; Kajihara, F; Kametani, S; Kamihara, N; Kamin, J; Kaneta, M; Kang, J H; Kanou, H; Kawagishi, T; Kawall, D; Kazantsev, A V; Kelly, S; Khanzadeev, A; Kikuchi, J; Kim, D H; Kim, D J; Kim, E; Kim, Y-S; Kinney, E; Kiss, A; Kistenev, E; Kiyomichi, A; Klay, J; Klein-Boesing, C; Kochenda, L; Kochetkov, V; Komkov, B; Konno, M; Kotchetkov, D; Kozlov, A; Král, A; Kravitz, A; Kroon, P J; Kubart, J; Kunde, G J; Kurihara, N; Kurita, K; Kweon, M J; Kwon, Y; Kyle, G S; Lacey, R; Lai, Y-S; Lajoie, J G; Lebedev, A; Le Bornec, Y; Leckey, S; Lee, D M; Lee, M K; Lee, T; Leitch, M J; Leite, M A L; Lenzi, B; Lim, H; Liska, T; Litvinenko, A; Liu, M X; Li, X; Li, X H; Love, B; Lynch, D; Maguire, C F; Makdisi, Y I; Malakhov, A; Malik, M D; Manko, V I; Mao, Y; Masek, L; Masui, H; Matathias, F; McCain, M C; McCumber, M; McGaughey, P L; Miake, Y; Mikes, P; Miki, K; Miller, T E; Milov, A; Mioduszewski, S; Mishra, G C; Mishra, M; Mitchell, J T; Mitrovski, M; Morreale, A; Morrison, D P; Moss, J M; Moukhanova, T V; Mukhopadhyay, D; Murata, J; Nagamiya, S; Nagata, Y; Nagle, J L; Naglis, M; Nakagawa, I; Nakamiya, Y; Nakamura, T; Nakano, K; Newby, J; Nguyen, M; Norman, B E; Nyanin, A S; Nystrand, J; O'Brien, E; Oda, S X; Ogilvie, C A; Ohnishi, H; Ojha, I D; Okada, H; Okada, K; Oka, M; Omiwade, O O; Oskarsson, A; Otterlund, I; Ouchida, M; Ozawa, K; Pak, R; Pal, D; Palounek, A P T; Pantuev, V; Papavassiliou, V; Park, J; Park, W J; Pate, S F; Pei, H; Peng, J-C; Pereira, H; Peresedov, V; Peressounko, D Yu; Pinkenburg, C; Pisani, R P; Purschke, M L; Purwar, A K; Qu, H; Rak, J; Rakotozafindrabe, A; Ravinovich, I; Read, K F; Rembeczki, S; Reuter, M; Reygers, K; Riabov, V; Riabov, Y; Roche, G; Romana, A; Rosati, M; Rosendahl, S S E; Rosnet, P; Rukoyatkin, P; Rykov, V L; Ryu, S S; Sahlmueller, B; Saito, N; Sakaguchi, T; Sakai, S; Sakata, H; Samsonov, V; Sato, H D; Sato, S; Sawada, S; Seele, J; Seidl, R; Semenov, V; Seto, R; Sharma, D; Shea, T K; Shein, I; Shevel, A; Shibata, T-A; Shigaki, K; Shimomura, M; Shohjoh, T; Shoji, K; Sickles, A; Silva, C L; Silvermyr, D; Silvestre, C; Sim, K S; Singh, C P; Singh, V; Skutnik, S; Slunecka, M; Smith, W C; Soldatov, A; Soltz, R A; Sondheim, W E; Sorensen, S P; Sourikova, I V; Staley, F; Stankus, P W; Stenlund, E; Stepanov, M; Ster, A; Stoll, S P; Sugitate, T; Suire, C; Sullivan, J P; Sziklai, J; Tabaru, T; Takagi, S; Takagui, E M; Taketani, A; Tanaka, K H; Tanaka, Y; Tanida, K; Tannenbaum, M J; Taranenko, A; Tarján, P; Thomas, T L; Togawa, M; Toia, A; Tojo, J; Tomásek, L; Torii, H; Towell, R S; Tram, V-N; Tserruya, I; Tsuchimoto, Y; Tuli, S K; Tydesjö, H; Tyurin, N; Vale, C; Valle, H; van Hecke, H W; Velkovska, J; Vertesi, R; Vinogradov, A A; Virius, M; Vrba, V; Vznuzdaev, E; Wagner, M; Walker, D; Wang, X R; Watanabe, Y; Wessels, J; White, S N; Willis, N; Winter, D; Woody, C L; Wysocki, M; Xie, W; Yamaguchi, Y L; Yanovich, A; Yasin, Z; Ying, J; Yokkaichi, S; Young, G R; Younus, I; Yushmanov, I E; Zajc, W A; Zaudtke, O; Zhang, C; Zhou, S; Zimányi, J; Zolin, L

    2008-12-01

    For Au + Au collisions at 200 GeV, we measure neutral pion production with good statistics for transverse momentum, pT, up to 20 GeV/c. A fivefold suppression is found, which is essentially constant for 5 < pT < 20 GeV/c. Experimental uncertainties are small enough to constrain any model-dependent parametrization for the transport coefficient of the medium, e.g., q in the parton quenching model. The spectral shape is similar for all collision classes, and the suppression does not saturate in Au + Au collisions. PMID:19113542

  5. Oligopeptide complex for targeted non-viral gene delivery to adipocytes

    NASA Astrophysics Data System (ADS)

    Won, Young-Wook; Adhikary, Partho Protim; Lim, Kwang Suk; Kim, Hyung Jin; Kim, Jang Kyoung; Kim, Yong-Hee

    2014-12-01

    Commercial anti-obesity drugs acting in the gastrointestinal tract or the central nervous system have been shown to have limited efficacy and severe side effects. Anti-obesity drug development is thus focusing on targeting adipocytes that store excess fat. Here, we show that an adipocyte-targeting fusion-oligopeptide gene carrier consisting of an adipocyte-targeting sequence and 9-arginine (ATS-9R) selectively transfects mature adipocytes by binding to prohibitin. Injection of ATS-9R into obese mice confirmed specific binding of ATS-9R to fat vasculature, internalization and gene expression in adipocytes. We also constructed a short-hairpin RNA (shRNA) for silencing fatty-acid-binding protein 4 (shFABP4), a key lipid chaperone in fatty-acid uptake and lipid storage in adipocytes. Treatment of obese mice with ATS-9R/shFABP4 led to metabolic recovery and body-weight reduction (>20%). The ATS-9R/shFABP4 oligopeptide complex could prove to be a safe therapeutic approach to regress and treat obesity as well as obesity-induced metabolic syndromes.

  6. Optimization of Enzymatic Production of Oligopeptides from Apricot Almonds Meal with Neutrase and N120P

    PubMed Central

    Wang, Chunyan; Wang, Qiang; Tian, Jinqiang

    2010-01-01

    Neutrase 0.8L and N120P proteases were used for oligopeptide production from apricot almonds meal, and response surface design was carried out to optimize the effect of hydrolysis conditions on hydrolysis degree (DH) and oligopeptide yield rate. Four independent variables were used to optimize the hydrolysis process: hydrolysis temperature (X1), enzyme-to substrate ratio (E/S) (X2), substrate concentration (X3) and reaction time (X4). Statistical analysis indicated that the four variables, quadratic terms of X1, X3, and X4, and the interaction terms with X1 had a significant (p < 0.05) effect on DH. The yield rate was also significantly affected by the four variables and quadratic terms of X1, X2 and X4. Two mathematical models with high determination coefficient were obtained and could be employed to optimize protein hydrolysis. The optimal hydrolysis conditions were determined as follows: hydrolysis temperature 52.5 °C; enzyme-to-substrate ratio (E/S) 7200 U/g; substrate concentration 2%; reaction time 173 min. The initial pH 6.5 and Neutrase-to-N120P dosage ratio 2:1 were fixed in this study according to the preliminary research. Under these conditions, the experimental DH and yield rate were 34.10 ± 5.25% and 72.42 ± 2.27%, respectively. PMID:21614184

  7. Directed self-assembly of π-conjugated oligopeptides for supramolecular electronics

    NASA Astrophysics Data System (ADS)

    Li, Bo; Li, Songsong; Zhou, Yuecheng; Tovar, John; Wilson, William; Schroeder, Charles

    The directed mesoscale engineering of nanoscale building blocks holds enormous promise to catalyze a revolution in new functional materials for advanced electronics. Bio-inspired systems can play a key role in this effort due to their inherent ``programmable'' function. In this work, oligopeptide with defined flanking sequences was appended to π-conjugated units, thereby directing their assembly processes in a designed manner. By utilizing custom-designed microfluidic devices and controlled acid vapor diffusion, the self-assembly rate was directed and precisely tuned. Notably, the kinetics was found to play a key role in the morphology of self-assembled π-conjugated oligopeptides. The influence of flanking peptide sequences and π-conjugated core-core interactions on the self-assembly nanostructure was systematically investigated. Importantly, the electronic properties of the synthetic peptide assembly was explored by integration as the active layer of a field effect transistor. The presented study offers insights to the design and fabrication of supramolecular electronics.

  8. Viscoelastic properties and nanoscale structures of composite oligopeptide-polysaccharide hydrogels.

    PubMed

    Hyland, Laura L; Taraban, Marc B; Feng, Yue; Hammouda, Boualem; Yu, Y Bruce

    2012-03-01

    Biocompatible and biodegradable peptide hydrogels are drawing increasing attention as prospective materials for human soft tissue repair and replacement. To improve the rather unfavorable mechanical properties of our pure peptide hydrogels, in this work we examined the possibility of creating a double hydrogel network. This network was created by means of the coassembly of mutually attractive, but self-repulsive oligopeptides within an already-existing fibrous network formed by the charged, biocompatible polysaccharides chitosan, alginate, and chondroitin. Using dynamic oscillatory rheology experiments, it was found that the coassembly of the peptides within the existing polysaccharide network resulted in a less stiff material as compared to the pure peptide networks (the elastic modulus G' decreased from 90 to 10 kPa). However, these composite oligopeptide-polysaccharide hydrogels were characterized by a greater resistance to deformation (the yield strain γ grew from 4 to 100%). Small-angle neutron scattering (SANS) was used to study the 2D cross-sectional shapes of the fibers, their dimensional characteristics, and the mesh sizes of the fibrous networks. Differences in material structures found with SANS experiments confirmed rheology data, showing that incorporation of the peptides dramatically changed the morphology of the polysaccharide network. The resulting fibers were structurally very similar to those forming the pure peptide networks, but formed less stiff gels because of their markedly greater mesh sizes. Together, these findings suggest an approach for the development of highly deformation-resistant biomaterials. PMID:21994046

  9. Focal accumulation of an apolipoprotein B-based synthetic oligopeptide in the healing rabbit arterial wall

    SciTech Connect

    Shih, I.L.; Lees, R.S.; Chang, M.Y.; Lees, A.M. )

    1990-02-01

    The functions of surface-accessible domains of apolipoprotein (apo) B, the protein moiety of low density lipoprotein (LDL), are unknown, aside from the LDL receptor-binding domain, which lies toward the carboxyl-terminal end of apoB. Since LDL accumulation in arterial lesions does not depend on recognition of LDLs by a cell-surface receptor, we synthesized an oligopeptide with the sequence of the trypsin-accessible domain of apoB that lies closest to the amino-terminal end of the protein and compared its biological activity to that of another synthetic oligopeptide with the sequence of the heparin- and apoB/apoE receptor-binding domains of apoE. (Tyrosine was added at the amino-terminal end of each peptide to facilitate radiolabeling.) The 18-amino acid apoB-based peptide included residues 1000-1016 of apoB, for which no function has been previously described. In radioautographs, the 125I-labeled peptide accumulated focally at the healing edges of regenerating endothelial islands in the balloon-catheter deendothelialized rabbit aorta. In contrast, the 21-residue apoE-based peptide, which included residues 129-148 of apoE, accumulated diffusely and uniformly throughout the deendothelialized areas of the aorta. The data show that focal binding of the apoB-based peptide can delineate arterial lesions and suggest that this arterial wall-binding domain of apoB mediates accumulation of LDLs in arterial lesions.

  10. Viscoelastic Properties and Nano-scale Structures of Composite Oligopeptide-Polysaccharide Hydrogels

    PubMed Central

    Hyland, Laura L.; Taraban, Marc B.; Feng, Yue; Hammouda, Boualem; Yu, Y. Bruce

    2012-01-01

    Biocompatible and biodegradable peptide hydrogels are drawing increasing attention as prospective materials for human soft tissue repair and replacement. To improve the rather unfavorable mechanical properties of our pure peptide hydrogels, in this work we examined the possibility of creating a double hydrogel network. This network was created by means of the co-assembly of mutually attractive but self-repulsive oligopeptides within an already existing fibrous network formed by the charged, biocompatible polysaccharides chitosan, alginate, and chondroitin. Using dynamic oscillatory rheology experiments, it was found that the co-assembly of the peptides within the existing polysaccharide network resulted in a less stiff material as compared to the pure peptide networks (the elastic modulus G′ decreased from 90 kPa to 10 kPa). However, these composite oligopeptide-polysaccharide hydrogels were characterized by a greater resistance to deformation (the yield strain γ grew from 4 % to 100 %). Small-angle neutron scattering (SANS) was used to study the 2D cross-sectional shapes of the fibers, their dimensional characteristics and the mesh sizes of the fibrous networks. Differences in material structures found with SANS experiments confirmed rheology data showing that incorporation of the peptides dramatically changed the morphology of the polysaccharide network. The resulting fibers were structurally very similar to those forming the pure peptide networks, but formedless stiff gels because of their markedly greater mesh sizes. Together, these findings suggest an approach for the development of highly deformation-resistant biomaterials. PMID:21994046

  11. Intercalation of amino acids and oligopeptides into Zn Al layered double hydroxide by coprecipitation reaction

    NASA Astrophysics Data System (ADS)

    Aisawa, Sumio; Sasaki, Shuji; Takahashi, Satoshi; Hirahara, Hidetoshi; Nakayama, Hirokazu; Narita, Eiichi

    2006-05-01

    The coprecipitation of amino acids and oligopeptides with the Zn Al LDH was investigated using phenylalanine (Phe), phenylalanyl-phenylalanine (Phe-Phe), glycyl-phenylalanine (Gly Phe), glycine (Gly), glycyl-glycine (Gly Gly), glycyl-glycyl-glycine (Gly Gly Gly) and N-(N-γ-glutamyl-cysteinyl)-glycine (GSH) as guest species. The coprecipitation behavior of amino acids and oligopeptides was found to be influenced by the solution pH and the kind of their side chain groups, and reached the maximum at pH 8 or 9. The basal spacing, d003, of the Phe, Phe-Phe and GSH/LDH was 1.81, 2.41 and 1.64 nm, supporting that guests were arranged vertical to the LDH basal layer. Acceding to the basal spacing of the Gly, Gly Gly and Gly Gly Gly/LDH (d003=0.84 0.88 nm), these guests were oriented horizontal to the LDH basal layer with the co-intercalated NO3-. Moreover, the amount of Phe-Phe, Gly Gly and Gly Gly Gly intercalated was almost the same as that of Phe and Gly despite increasing the number peptide bond and the molecular size. GSH was intercalated into the LDH interlayer space as GSH oxidized form with bridged LDH layers by their carboxylate groups.

  12. Linoleic acid suppresses cholesterol efflux and ATP-binding cassette transporters in murine bone marrow-derived macrophages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Individuals with type 2 diabetes mellitus (T2DM) are at increased risk of developing cardiovascular disease (CVD), possibly associated with elevated plasma free fatty acid concentrations. Paradoxically, evidence suggests that unsaturated, compared to saturated fatty acids, suppress macrophage chole...

  13. Cell Lysis in S. pombe ura4 Mutants Is Suppressed by Loss of Functional Pub1, Which Regulates the Uracil Transporter Fur4

    PubMed Central

    Nishino, Kohei; Kushima, Misaki; Matsuo, Yuzy; Matsuo, Yasuhiro; Kawamukai, Makoto

    2015-01-01

    Schizosaccharomyces pombe Δura4 cells lyse when grown on YPD medium. A S. pombe non-essential gene deletion library was screened to determine suppressors of the lysis phenotype. Deletion of the pub1 gene, which encoded E3 ubiquitin ligase, strongly suppressed cell lysis in Δura4 cells. The Δpub1 cells displayed high sensitivity to 5-fluorouracil, a toxic analog of uracil, and this sensitivity was suppressed by deletion of fur4, which encoded a uracil transporter. Fur4 localized primarily to the Golgi apparatus and vacuoles in wild-type cells, but localization was predominantly at the plasma membrane in Δpub1 cells. Fur4 was necessary for the utilization of extracellular uracil, cytosine, or UMP. Uracil uptake activity increased in the Δpub1 strain in a Fur4-dependent manner. In addition, uracil starvation was critical for induction of cell lysis of Δura4 strains and uracil supplementation suppressed lysis. In summary, the increased uracil uptake ability of Δpub1 cells, where Fur4 was predominantly localized to the plasma membrane, resulted in suppression of cell lysis in the Δura4 background. PMID:26536126

  14. Chemical and enzymatic catalytic routes to polyesters and oligopeptides biobased materials

    NASA Astrophysics Data System (ADS)

    Zhu, Jianhui

    My Ph.D research focuses on the synthesis and property studies of different biobased materials, including polyesters, polyurethanes and oligopeptides. The first study describes the synthesis, crystal structure and physico-mechanical properties of a bio-based polyester prepared from 2,5-furandicarboxylic acid (FDCA) and 1,4-butanediol. Melt-polycondensation experiments were conducted by a two-stage polymerization using titanium tetraisopropoxide (Ti[OiPr] 4) as catalyst. Polymerization conditions (catalyst concentration, reaction time and 2nd stage reaction temperature) were varied to optimize poly(butylene furan dicarboxylate), PBF, molecular weight. A series of PBFs with different Mw were characterized by Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Dynamic Mechanical Thermal Analysis (DMTA), X-Ray diffraction and tensile testing. Influence of molecular weight and melting/crystallization enthalpy on PBF material tensile properties was explored. Cold-drawing tensile tests at room temperature for PBF with Mw 16K to 27K showed a brittle-to-ductile transition. When Mw reaches 38K, the Young's Modulus of PBF remains above 900 MPa, and the elongation at break increases to above 1000%. The mechanical properties, thermal properties and crystal structures of PBF were similar to petroleum derived poly(butylenes terephthalate), PBT. Fiber diagrams of uniaxially stretched PBF films were collected, indexed, and the unit cell was determined as triclinic (a=4.78(3) A, b=6.03(5) A, c=12.3(1) A, alpha=110.1(2)°, beta=121.1(3)°, gamma=100.6(2)°). A crystal structure was derived from this data and final atomic coordinates are reported. We concluded that there is a close similarity of the PBF structure to PBT alpha- and beta-forms. In the second study, a biobased long chain polyester polyol (PC14-OH) was synthesized from o-hydroxytetradecanoic acid (o-HOC14) and 1,4-butanediol. The first section about polyester polyurethanes describes the synthesis

  15. Structural Analysis of Semi-specific Oligosaccharide Recognition by a Cellulose-binding Protein of Thermotoga maritima Reveals Adaptations for Functional Diversification of the Oligopeptide Periplasmic Binding Protein Fold

    SciTech Connect

    Cuneo, Matthew J.; Beese, Lorena S.; Hellinga, Homme W.

    2010-05-25

    Periplasmic binding proteins (PBPs) constitute a protein superfamily that binds a wide variety of ligands. In prokaryotes, PBPs function as receptors for ATP-binding cassette or tripartite ATP-independent transporters and chemotaxis systems. In many instances, PBPs bind their cognate ligands with exquisite specificity, distinguishing, for example, between sugar epimers or structurally similar anions. By contrast, oligopeptide-binding proteins bind their ligands through interactions with the peptide backbone but do not distinguish between different side chains. The extremophile Thermotoga maritima possesses a remarkable array of carbohydrate-processing metabolic systems, including the hydrolysis of cellulosic polymers. Here, we present the crystal structure of a T. maritima cellobiose-binding protein (tm0031) that is homologous to oligopeptide-binding proteins. T. maritima cellobiose-binding protein binds a variety of lengths of {beta}(1 {yields} 4)-linked glucose oligomers, ranging from two rings (cellobiose) to five (cellopentaose). The structure reveals that binding is semi-specific. The disaccharide at the nonreducing end binds specifically; the other rings are located in a large solvent-filled groove, where the reducing end makes several contacts with the protein, thereby imposing an upper limit of the oligosaccharides that are recognized. Semi-specific recognition, in which a molecular class rather than individual species is selected, provides an efficient solution for the uptake of complex mixtures.

  16. 30 CFR 75.1911 - Fire suppression systems for diesel-powered equipment and fuel transportation units.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... dry chemical type (ABC) fire suppression system listed or approved by a nationally recognized independent testing laboratory and appropriate for installation on diesel-powered equipment and fuel... required by the nationally recognized independent testing laboratory listing or approval, and be...

  17. Suppression of roll-off characteristics of organic light-emitting diodes by narrowing current injection/transport area to 50 nm

    SciTech Connect

    Hayashi, Kyohei Inoue, Munetomo; Yoshida, Kou; Nakanotani, Hajime; Mikhnenko, Oleksandr; Nguyen, Thuc-Quyen E-mail: adachi@cstf.kyushu-u.ac.jp; Adachi, Chihaya E-mail: adachi@cstf.kyushu-u.ac.jp

    2015-03-02

    Using e-beam nanolithography, the current injection/transport area in organic light-emitting diodes (OLEDs) was confined into a narrow linear structure with a minimum width of 50 nm. This caused suppression of Joule heating and partial separation of polarons and excitons, so the charge density where the electroluminescent efficiency decays to the half of the initial value (J{sub 0}) was significantly improved. A device with a narrow current injection width of 50 nm exhibited a J{sub 0} that was almost two orders of magnitude higher compared with that of the unpatterned OLED.

  18. Suppression of NDA-Type Alternative Mitochondrial NAD(P)H Dehydrogenases in Arabidopsis thaliana Modifies Growth and Metabolism, but not High Light Stimulation of Mitochondrial Electron Transport

    PubMed Central

    Wallström, Sabá V.; Florez-Sarasa, Igor; Araújo, Wagner L.; Escobar, Matthew A.; Geisler, Daniela A.; Aidemark, Mari; Lager, Ida; Fernie, Alisdair R.; Ribas-Carbó, Miquel; Rasmusson, Allan G.

    2014-01-01

    The plant respiratory chain contains several pathways which bypass the energy-conserving electron transport complexes I, III and IV. These energy bypasses, including type II NAD(P)H dehydrogenases and the alternative oxidase (AOX), may have a role in redox stabilization and regulation, but current evidence is inconclusive. Using RNA interference, we generated Arabidopsis thaliana plants simultaneously suppressing the type II NAD(P)H dehydrogenase genes NDA1 and NDA2. Leaf mitochondria contained substantially reduced levels of both proteins. In sterile culture in the light, the transgenic lines displayed a slow growth phenotype, which was more severe when the complex I inhibitor rotenone was present. Slower growth was also observed in soil. In rosette leaves, a higher NAD(P)H/NAD(P)+ ratio and elevated levels of lactate relative to sugars and citric acid cycle metabolites were observed. However, photosynthetic performance was unaffected and microarray analyses indicated few transcriptional changes. A high light treatment increased AOX1a mRNA levels, in vivo AOX and cytochrome oxidase activities, and levels of citric acid cycle intermediates and hexoses in all genotypes. However, NDA-suppressing plants deviated from the wild type merely by having higher levels of several amino acids. These results suggest that NDA suppression restricts citric acid cycle reactions, inducing a shift towards increased levels of fermentation products, but do not support a direct association between photosynthesis and NDA proteins. PMID:24486764

  19. Chemical and enzymatic catalytic routes to polyesters and oligopeptides biobased materials

    NASA Astrophysics Data System (ADS)

    Zhu, Jianhui

    My Ph.D research focuses on the synthesis and property studies of different biobased materials, including polyesters, polyurethanes and oligopeptides. The first study describes the synthesis, crystal structure and physico-mechanical properties of a bio-based polyester prepared from 2,5-furandicarboxylic acid (FDCA) and 1,4-butanediol. Melt-polycondensation experiments were conducted by a two-stage polymerization using titanium tetraisopropoxide (Ti[OiPr] 4) as catalyst. Polymerization conditions (catalyst concentration, reaction time and 2nd stage reaction temperature) were varied to optimize poly(butylene furan dicarboxylate), PBF, molecular weight. A series of PBFs with different Mw were characterized by Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Dynamic Mechanical Thermal Analysis (DMTA), X-Ray diffraction and tensile testing. Influence of molecular weight and melting/crystallization enthalpy on PBF material tensile properties was explored. Cold-drawing tensile tests at room temperature for PBF with Mw 16K to 27K showed a brittle-to-ductile transition. When Mw reaches 38K, the Young's Modulus of PBF remains above 900 MPa, and the elongation at break increases to above 1000%. The mechanical properties, thermal properties and crystal structures of PBF were similar to petroleum derived poly(butylenes terephthalate), PBT. Fiber diagrams of uniaxially stretched PBF films were collected, indexed, and the unit cell was determined as triclinic (a=4.78(3) A, b=6.03(5) A, c=12.3(1) A, alpha=110.1(2)°, beta=121.1(3)°, gamma=100.6(2)°). A crystal structure was derived from this data and final atomic coordinates are reported. We concluded that there is a close similarity of the PBF structure to PBT alpha- and beta-forms. In the second study, a biobased long chain polyester polyol (PC14-OH) was synthesized from o-hydroxytetradecanoic acid (o-HOC14) and 1,4-butanediol. The first section about polyester polyurethanes describes the synthesis

  20. Investigation Into Efficiency of a Novel Glycol Chitosan-Bestatin Conjugate to Protect Thymopoietin Oligopeptides From Enzymatic Degradation.

    PubMed

    Zhang, Yong; Feng, Jiao; Cui, Lili; Zhang, Yuebin; Li, Wenzhao; Li, Chunlei; Shi, Nianqiu; Chen, Yan; Kong, Wei

    2016-02-01

    In this study, a novel glycol chitosan (GCS)-bestatin conjugate was synthesized and evaluated to demonstrate its efficacy in protecting thymopoietin oligopeptides from aminopeptidase-mediated degradation. Moreover, the mechanism and relative susceptibility of three thymopoietin oligopeptides, thymocartin (TP4), thymopentin (TP5), and thymotrinan (TP3), to enzymatic degradation were investigated and compared at the molecular level. Initial investigations indicated that formation of the GCS-bestatin conjugate, with a substitution degree of 7.0% (moles of bestatin per mole of glycol glucosamine unit), could significantly protect all 3 peptides from aminopeptidase-mediated degradation in a concentration-dependent manner. The space hindrance and loss of one pair of hydrogen bonds, resulting from the covalent conjugation of chitosan with bestatin, did not affect the specific interaction between bestatin and aminopeptidase. Moreover, TP4 displayed a higher degradation clearance compared with those of TP5 and TP3 under the same experimental conditions. The varying levels of susceptibility of these 3 peptides to aminopeptidase (TP4 > TP5 > TP3) were closely related to differences in their binding energies to enzyme, which mainly involved Van der Waals forces and electrostatic interactions, as supported by the results of molecular dynamics simulations. These results suggest that GCS-bestatin conjugate might be useful in the delivery of thymopoietin oligopeptides by mucosal routes, and that TP3 and TP5 are better alternatives to TP4 for delivery because of their robust resistance against enzymatic degradation. PMID:26173563

  1. Application of reverse-phase HPLC to quantify oligopeptide acetylation eliminates interference from unspecific acetyl CoA hydrolysis

    PubMed Central

    Evjenth, Rune; Hole, Kristine; Ziegler, Mathias; Lillehaug, Johan R

    2009-01-01

    Protein acetylation is a common modification that plays a central role in several cellular processes. The most widely used methods to study these modifications are either based on the detection of radioactively acetylated oligopetide products or an enzyme-coupled reaction measuring conversion of the acetyl donor acetyl CoA to the product CoASH. Due to several disadvantages of these methods, we designed a new method to study oligopeptide acetylation. Based on reverse phase HPLC we detect both reaction products in a highly robust and reproducible way. The method reported here is also fully compatible with subsequent product analysis, e.g. by mass spectroscopy. The catalytic subunit, hNaa30p, of the human NatC protein N-acetyltransferase complex was used for N-terminal oligopeptide acetylation. We show that unacetylated and acetylated oligopeptides can be efficiently separated and quantified by the HPLC-based analysis. The method is highly reproducible and enables reliable quantification of both substrates and products. It is therefore well-suited to determine kinetic parameters of acetyltransferases. PMID:19660098

  2. Suppression of asymmetric acid efflux and gravitropism in maize roots treated with auxin transport inhibitors of sodium orthovanadate

    NASA Technical Reports Server (NTRS)

    Mulkey, T. J.; Evans, M. L.

    1982-01-01

    In gravitropically stimulated roots of maize (Zea mays L., hybrid WF9 x 38MS), there is more acid efflux on the rapidly growing upper side than on the slowly growing lower side. In light of the Cholodny/Went hypothesis of gravitropism which states that gravitropic curvature results from lateral redistribution of auxin, the effects of auxin transport inhibitors on the development of acid efflux asymmetry and curvature in gravistimulated roots were examined. All the transport inhibitors tested prevented both gravitropism and the development of asymmetric acid efflux in gravistimulated roots. The results indicate that auxin redistribution may cause the asymmetry of acid efflux, a finding consistent with the Cholodny/Went hypothesis of gravitropism. As further evidence that auxin-induced acid efflux asymmetry may mediate gravitropic curvature, sodium orthovanadate, an inhibitor of auxin-induced H+ efflux was found to prevent both gravitropism and the development of asymmetric acid efflux in gravistimulated roots.

  3. Suppressing electron turbulence and triggering internal transport barriers with reversed magnetic shear in the National Spherical Torus Experimenta)

    NASA Astrophysics Data System (ADS)

    Peterson, J. L.; Bell, R.; Candy, J.; Guttenfelder, W.; Hammett, G. W.; Kaye, S. M.; LeBlanc, B.; Mikkelsen, D. R.; Smith, D. R.; Yuh, H. Y.

    2012-05-01

    The National Spherical Torus Experiment (NSTX) [M. Ono et al., Nucl. Fusion 40, 557 (2000)] can achieve high electron plasma confinement regimes that are super-critically unstable to the electron temperature gradient driven (ETG) instability. These plasmas, dubbed electron internal transport barriers (e-ITBs), occur when the magnetic shear becomes strongly negative. Using the gyrokinetic code GYRO [J. Candy and R. E. Waltz, J. Comput. Phys. 186, 545 (2003)], the first nonlinear ETG simulations of NSTX e-ITB plasmas reinforce this observation. Local simulations identify a strongly upshifted nonlinear critical gradient for thermal transport that depends on magnetic shear. Global simulations show e-ITB formation can occur when the magnetic shear becomes strongly negative. While the ETG-driven thermal flux at the outer edge of the barrier is large enough to be experimentally relevant, the turbulence cannot propagate past the barrier into the plasma interior.

  4. Suppressing electron turbulence and triggering internal transport barriers with reversed magnetic shear in the National Spherical Torus Experiment

    SciTech Connect

    Peterson, J. L.; Bell, R.; Guttenfelder, W.; Hammett, G. W.; Kaye, S. M.; LeBlanc, B.; Mikkelsen, D. R.; Candy, J.; Smith, D. R.; Yuh, H. Y.

    2012-05-15

    The National Spherical Torus Experiment (NSTX) [M. Ono et al., Nucl. Fusion 40, 557 (2000)] can achieve high electron plasma confinement regimes that are super-critically unstable to the electron temperature gradient driven (ETG) instability. These plasmas, dubbed electron internal transport barriers (e-ITBs), occur when the magnetic shear becomes strongly negative. Using the gyrokinetic code GYRO [J. Candy and R. E. Waltz, J. Comput. Phys. 186, 545 (2003)], the first nonlinear ETG simulations of NSTX e-ITB plasmas reinforce this observation. Local simulations identify a strongly upshifted nonlinear critical gradient for thermal transport that depends on magnetic shear. Global simulations show e-ITB formation can occur when the magnetic shear becomes strongly negative. While the ETG-driven thermal flux at the outer edge of the barrier is large enough to be experimentally relevant, the turbulence cannot propagate past the barrier into the plasma interior.

  5. Tumor Cellular Proteasome Inhibition and Growth Suppression by 8-Hydroxyquinoline and Clioquinol Requires Their Capabilities to Bind Copper and Transport Copper into Cells

    PubMed Central

    Zhai, Shumei; Yang, Lei; Cui, Qiuzhi Cindy; Sun, Ying; Dou, Q. Ping; Yan, Bing

    2009-01-01

    We have previously reported that when mixed with copper, 8-hydroxyquinoline (8-OHQ) and its analog clioquinol (CQ) inhibited the proteasomal activity and proliferation in cultured human cancer cells. CQ treatment of high copper-containing human tumor xenografts also caused cancer suppression, associated with proteasome inhibition in vivo. However, the nature of copper dependence of these events has not been elucidated experimentally. In the current study, by using chemical probe molecules that mimic structures of 8-OHQ and CQ, but have no copper binding capability, we dissected the complex cellular processes elicited by 8-OHQ-Cu or CQ-Cu mixture and revealed that copper-binding to 8-OHQ or CQ is required for transportation of copper complex into human breast cancer cells and the consequent proteasome-inhibitory, growth-suppressive and apoptosis-inducing activities. In contrast, the non-copper-binding analogs of 8-OHQ or CQ blocked the very first step – copper binding in this chain of events mediated by 8-OHQ-Cu or CQ-Cu. PMID:19809836

  6. Abiotic Protein Fragmentation by Manganese Oxide: Implications for a Mechanism to Supply Soil Biota with Oligopeptides.

    PubMed

    Reardon, Patrick N; Chacon, Stephany S; Walter, Eric D; Bowden, Mark E; Washton, Nancy M; Kleber, Markus

    2016-04-01

    The ability of plants and microorganisms to take up organic nitrogen in the form of free amino acids and oligopeptides has received increasing attention over the last two decades, yet the mechanisms for the formation of such compounds in soil environments remain poorly understood. We used Nuclear Magnetic Resonance (NMR) and Electron Paramagnetic Resonance (EPR) spectroscopies to distinguish the reaction of a model protein with a pedogenic oxide (Birnessite, MnO2) from its response to a phyllosilicate (Kaolinite). Our data demonstrate that birnessite fragments the model protein while kaolinite does not, resulting in soluble peptides that would be available to soil biota and confirming the existence of an abiotic pathway for the formation of organic nitrogen compounds for direct uptake by plants and microorganisms. The absence of reduced Mn(II) in the solution suggests that birnessite acts as a catalyst rather than an oxidant in this reaction. NMR and EPR spectroscopies are shown to be valuable tools to observe these reactions and capture the extent of protein transformation together with the extent of mineral response. PMID:26974439

  7. Polyamidoamine (PAMAM) dendrimers modified with short oligopeptides for early endosomal escape and enhanced gene delivery.

    PubMed

    Thuy, Le Thi; Mallick, Sudipta; Choi, Joon Sig

    2015-08-15

    Recently, non-viral vectors have become a popular research topic in the field of gene therapy. In this study, we conjugated short oligopeptides to polyamidoamine-generation 4 (PAMAM G4) to achieve higher transfection efficiency. Previous reports have shown that the PAMAM G4-histidine (H)-arginine (R) dendrimer enhances gene delivery by improving cell penetration and internalization mechanisms. Therefore, we synthesized PAMAM G4-H phenylalanine (F) R, PAMAM G4-FHR and PAMAM G4-FR derivatives to determine the best gene carrier with the lowest toxicity. Physicochemical studies were performed to determine mean diameters and surface charge of PAMAM derivatives/pDNA polyplexes. DNA condensation was confirmed using a gel retardation assay. Cytotoxicity and transfection efficiency were analyzed using human cervical carcinoma (HeLa) and human liver carcinoma (HepG2) cells. Similar levels of transfection were achieved in both cell lines by using gold standard transfection reagent PEI 25 kD. Therefore, our results show that these carriers are promising and may help achieve higher transfection with negligible cytotoxicity. PMID:26187169

  8. Crystal structure of a putative oligopeptide-binding periplasmic protein from a hyperthermophile.

    PubMed

    Yoon, Hye-Jin; Kim, Hee Jung; Mikami, Bunzo; Yu, Yeon Gyu; Lee, Hyung Ho

    2016-09-01

    Oligopeptide-binding proteins (Opps) are part of the ATP-binding cassette system, playing a crucial role in nutrient uptake and sensing the external environment in bacteria, including hyperthermophiles. Opps serve as a binding platform for diverse peptides; however, how these peptides are recognized by Opps is still largely unknown and few crystal structures of Opps from hyperthermophiles have been determined. To facilitate such an understanding, the crystal structure of a putative Opp, OppA from Thermotoga maritima (TmOppA), was solved at 2.6-Å resolution in the open conformation. TmOppA is composed of three domains. The N-terminal domain consists of twelve strands, nine helices, and four 310 helices, and the C-terminal domain consists of five strands, ten helices, and one 310 helix. These two domains are connected by the linker domain, which consists of two strands, three helices, and three 310 helices. Based on structural comparisons of TmOppA with other OppAs and binding studies, we suggest that TmOppA might be a periplasmic Opp. The most distinct feature of TmOppA is the insertion of two helices, which are lacking in other OppAs. A cavity volume between the N-terminal and C-terminal domains is suggested to be responsible for binding peptides of various lengths. PMID:27377296

  9. Protective Effects of Soy Oligopeptides in Ultraviolet B-Induced Acute Photodamage of Human Skin

    PubMed Central

    Ma, Li-wen; Liu, Juan; Zhang, Jia-an; Xu, Yang; Wu, Di; Permatasari, Felicia

    2016-01-01

    Aim. We explored the effects of soy oligopeptides (SOP) in ultraviolet B- (UVB-) induced acute photodamage of human skin in vivo and foreskin ex vivo. Methods. We irradiated the forearm with 1.5 minimal erythemal dose (MED) of UVB for 3 consecutive days, establishing acute photodamage of skin, and topically applied SOP. Erythema index (EI), melanin index, stratum corneum hydration, and transepidermal water loss were measured by using Multiprobe Adapter 9 device. We irradiated foreskin ex vivo with the same dose of UVB (180 mJ/cm2) for 3 consecutive days and topically applied SOP. Sunburn cells were detected by using hematoxylin and eosin staining. Apoptotic cells were detected by using terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Cyclobutane pyrimidine dimers (CPDs), p53 protein, Bax protein, and Bcl-2 protein were detected by using immunohistochemical staining. Results. Compared with UVB group, UVB-irradiated skin with topically applied SOP showed significantly decreased EI. Compared with UVB group, topical SOP significantly increased Bcl-2 protein expression and decreased CPDs-positive cells, sunburn cells, apoptotic cells, p53 protein expression, and Bax protein expressions in the epidermis of UVB-irradiated foreskin. Conclusion. Our study demonstrated that topical SOP can protect human skin against UVB-induced photodamage. PMID:27478534

  10. Protective Effects of Soy Oligopeptides in Ultraviolet B-Induced Acute Photodamage of Human Skin.

    PubMed

    Zhou, Bing-Rong; Ma, Li-Wen; Liu, Juan; Zhang, Jia-An; Xu, Yang; Wu, Di; Permatasari, Felicia; Luo, Dan

    2016-01-01

    Aim. We explored the effects of soy oligopeptides (SOP) in ultraviolet B- (UVB-) induced acute photodamage of human skin in vivo and foreskin ex vivo. Methods. We irradiated the forearm with 1.5 minimal erythemal dose (MED) of UVB for 3 consecutive days, establishing acute photodamage of skin, and topically applied SOP. Erythema index (EI), melanin index, stratum corneum hydration, and transepidermal water loss were measured by using Multiprobe Adapter 9 device. We irradiated foreskin ex vivo with the same dose of UVB (180 mJ/cm(2)) for 3 consecutive days and topically applied SOP. Sunburn cells were detected by using hematoxylin and eosin staining. Apoptotic cells were detected by using terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Cyclobutane pyrimidine dimers (CPDs), p53 protein, Bax protein, and Bcl-2 protein were detected by using immunohistochemical staining. Results. Compared with UVB group, UVB-irradiated skin with topically applied SOP showed significantly decreased EI. Compared with UVB group, topical SOP significantly increased Bcl-2 protein expression and decreased CPDs-positive cells, sunburn cells, apoptotic cells, p53 protein expression, and Bax protein expressions in the epidermis of UVB-irradiated foreskin. Conclusion. Our study demonstrated that topical SOP can protect human skin against UVB-induced photodamage. PMID:27478534

  11. Oligopeptide elicitor-mediated defense gene activation in cultured parsley cells.

    PubMed Central

    Hahlbrock, K; Scheel, D; Logemann, E; Nürnberger, T; Parniske, M; Reinold, S; Sacks, W R; Schmelzer, E

    1995-01-01

    We have used suspension-cultured parsley cells (Petroselinum crispum) and an oligopeptide elicitor derived from a surface glycoprotein of the phytopathogenic fungus Phytophthora megasperma f.sp. glycinea to study the signaling pathway from elicitor recognition to defense gene activation. Immediately after specific binding of the elicitor by a receptor in the plasma membrane, large and transient increases in several inorganic ion fluxes (Ca2+, H+, K+, Cl-) and H2O2 formation are the first detectable plant cell responses. These are rapidly followed by transient changes in the phosphorylation status of various proteins and by the activation of numerous defense-related genes, concomitant with the inactivation of several other, non-defense-related genes. A great diversity of cis-acting elements and trans-acting factors appears to be involved in elicitor-mediated gene regulation, similar to the apparently complex nature of the signal transduced intracellularly. With few exceptions, all individual defense responses analyzed in fungus-infected parsley leaves have been found to be closely mimicked in elicitor-treated, cultured parsley cells, thus validating the use of the elicitor/cell culture system as a valuable model system for these types of study. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:7753777

  12. Thermodynamics, morphology, and kinetics of early- stage self-assembly of pi-conjugated oligopeptides

    NASA Astrophysics Data System (ADS)

    Thurston, Bryce; Tovar, John; Ferguson, Andrew

    Synthetic oligopeptides containing π-conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterize an implicit solvent model to simulate self-assembly. At low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ~ - 25kB T . Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini. We model simulations of hundereds of monomers as a continuous-time Markov process. We infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates. Supported by U.S. Department of Energy, Office of Science, Basic Energy Sciences, Award DE-SC0004857. Molecular simulations partially conducted on University of Illinois Computational Science and Engineering Program parallel computing resources.

  13. Mammalian ion-coupled solute transporters.

    PubMed Central

    Hediger, M A; Kanai, Y; You, G; Nussberger, S

    1995-01-01

    Active transport of solutes into and out of cells proceeds via specialized transporters that utilize diverse energy-coupling mechanisms. Ion-coupled transporters link uphill solute transport to downhill electrochemical ion gradients. In mammals, these transporters are coupled to the co-transport of H+, Na+, Cl- and/or to the countertransport of K+ or OH-. By contrast, ATP-dependent transporters are directly energized by the hydrolysis of ATP. The development of expression cloning approaches to select cDNA clones solely based on their capacity to induce transport function in Xenopus oocytes has led to the cloning of several ion-coupled transporter cDNAs and revealed new insights into structural designs, energy-coupling mechanisms and physiological relevance of the transporter proteins. Different types of mammalian ion-coupled transporters are illustrated by discussing transporters isolated in our own laboratory such as the Na+/glucose co-transporters SGLT1 and SGLT2, the H(+)-coupled oligopeptide transporters PepT1 and PepT2, and the Na(+)- and K(+)-dependent neuronal and epithelial high affinity glutamate transporter EAAC1. Most mammalian ion-coupled organic solute transporters studied so far can be grouped into the following transporter families: (1) the predominantly Na(+)-coupled transporter family which includes the Na+/glucose co-transporters SGLT1, SGLT2, SGLT3 (SAAT-pSGLT2) and the inositol transporter SMIT, (2) the Na(+)- and Cl(-)-coupled transporter family which includes the neurotransmitter transporters of gamma-amino-butyric acid (GABA), serotonin, dopamine, norepinephrine, glycine and proline as well as transporters of beta-amino acids, (3) the Na(+)- and K(+)-dependent glutamate/neurotransmitter family which includes the high affinity glutamate transporters EAAC1, GLT-1, GLAST, EAAT4 and the neutral amino acid transporters ASCT1 and SATT1 reminiscent of system ASC and (4) the H(+)-coupled oligopeptide transporter family which includes the intestinal H

  14. Transport phenomena in intrinsic semiconductors and insulators at high current densities: Suppression of the broken neutrality drift

    SciTech Connect

    Mnatsakanov, T. T.; Tandoev, A. G.; Yurkov, S. N.; Levinshtein, M. E.

    2013-08-14

    It is shown that, in addition to the diffusion and broken neutrality drift (BND) modes well-known for insulators and very lightly doped semiconductors, the quasineutral drift (QND) mode is possible. The transition from the BND to QND mode is accompanied by the appearance of a portion with a very sharp current rise in the current-voltage characteristic. This effect is observed in a new type of semiconductor detectors (CIDs, Current Injected Detectors) of high-intensity neutron and proton radiation, suggested, in particular, for Large Hadron Collider. The effect is unambiguously attributed now to the presence of radiation-induced deep centers in a semiconductor. It is shown, however, in this paper that the effect of a very sharp rise in current upon a slight increase in voltage is even possible when there are no deep centers. An equation adequately describing the possible transport modes in intrinsic semiconductors and insulators is derived. The results of an analytical study are confirmed by an adequate simulation.

  15. Transport phenomena in intrinsic semiconductors and insulators at high current densities: Suppression of the broken neutrality drift

    NASA Astrophysics Data System (ADS)

    Mnatsakanov, T. T.; Levinshtein, M. E.; Tandoev, A. G.; Yurkov, S. N.

    2013-08-01

    It is shown that, in addition to the diffusion and broken neutrality drift (BND) modes well-known for insulators and very lightly doped semiconductors, the quasineutral drift (QND) mode is possible. The transition from the BND to QND mode is accompanied by the appearance of a portion with a very sharp current rise in the current-voltage characteristic. This effect is observed in a new type of semiconductor detectors (CIDs, Current Injected Detectors) of high-intensity neutron and proton radiation, suggested, in particular, for Large Hadron Collider. The effect is unambiguously attributed now to the presence of radiation-induced deep centers in a semiconductor. It is shown, however, in this paper that the effect of a very sharp rise in current upon a slight increase in voltage is even possible when there are no deep centers. An equation adequately describing the possible transport modes in intrinsic semiconductors and insulators is derived. The results of an analytical study are confirmed by an adequate simulation.

  16. A Novel Vasoactive Proline-Rich Oligopeptide from the Skin Secretion of the Frog Brachycephalus ephippium.

    PubMed

    Arcanjo, Daniel Dias Rufino; Vasconcelos, Andreanne Gomes; Comerma-Steffensen, Simón Gabriel; Jesus, Joilson Ramos; Silva, Luciano Paulino; Pires Júnior, Osmindo Rodrigues; Costa-Neto, Claudio Miguel; Oliveira, Eduardo Brandt; Migliolo, Ludovico; Franco, Octávio Luiz; Restini, Carolina Baraldi Araújo; Paulo, Michele; Bendhack, Lusiane Maria; Bemquerer, Marcelo Porto; Oliveira, Aldeidia Pereira; Simonsen, Ulf; Leite, José Roberto de Souza de Almeida

    2015-01-01

    Proline-rich oligopeptides (PROs) are a large family which comprises the bradykinin-potentiating peptides (BPPs). They inhibit the activity of the angiotensin I-converting enzyme (ACE) and have a typical pyroglutamyl (Pyr)/proline-rich structure at the N- and C-terminus, respectively. Furthermore, PROs decrease blood pressure in animals. In the present study, the isolation and biological characterization of a novel vasoactive BPP isolated from the skin secretion of the frog Brachycephalus ephippium is described. This new PRO, termed BPP-Brachy, has the primary structure WPPPKVSP and the amidated form termed BPP-BrachyNH2 inhibits efficiently ACE in rat serum. In silico molecular modeling and docking studies suggest that BPP-BrachyNH2 is capable of forming a hydrogen bond network as well as multiple van der Waals interactions with the rat ACE, which blocks the access of the substrate to the C-domain active site. Moreover, in rat thoracic aorta BPP-BrachyNH2 induces potent endothelium-dependent vasodilatation with similar magnitude as captopril. In DAF-FM DA-loaded aortic cross sections examined by confocal microscopy, BPP-BrachyNH2 was found to increase the release of nitric oxide (NO). Moreover, BPP-BrachyNH2 was devoid of toxicity in endothelial and smooth muscle cell cultures. In conclusion, the peptide BPP-BrachyNH2 has a novel sequence being the first BPP isolated from the skin secretion of the Brachycephalidae family. This opens for exploring amphibians as a source of new biomolecules. The BPP-BrachyNH2 is devoid of cytotoxicity and elicits endothelium-dependent vasodilatation mediated by NO. These findings open for the possibility of potential application of these peptides in the treatment of endothelial dysfunction and cardiovascular diseases. PMID:26661890

  17. A Novel Vasoactive Proline-Rich Oligopeptide from the Skin Secretion of the Frog Brachycephalus ephippium

    PubMed Central

    Arcanjo, Daniel Dias Rufino; Vasconcelos, Andreanne Gomes; Comerma-Steffensen, Simón Gabriel; Jesus, Joilson Ramos; Silva, Luciano Paulino; Pires, Osmindo Rodrigues; Costa-Neto, Claudio Miguel; Oliveira, Eduardo Brandt; Migliolo, Ludovico; Franco, Octávio Luiz; Restini, Carolina Baraldi Araújo; Paulo, Michele; Bendhack, Lusiane Maria; Bemquerer, Marcelo Porto; Oliveira, Aldeidia Pereira; Simonsen, Ulf; Leite, José Roberto de Souza de Almeida

    2015-01-01

    Proline-rich oligopeptides (PROs) are a large family which comprises the bradykinin-potentiating peptides (BPPs). They inhibit the activity of the angiotensin I-converting enzyme (ACE) and have a typical pyroglutamyl (Pyr)/proline-rich structure at the N- and C-terminus, respectively. Furthermore, PROs decrease blood pressure in animals. In the present study, the isolation and biological characterization of a novel vasoactive BPP isolated from the skin secretion of the frog Brachycephalus ephippium is described. This new PRO, termed BPP-Brachy, has the primary structure WPPPKVSP and the amidated form termed BPP-BrachyNH2 inhibits efficiently ACE in rat serum. In silico molecular modeling and docking studies suggest that BPP-BrachyNH2 is capable of forming a hydrogen bond network as well as multiple van der Waals interactions with the rat ACE, which blocks the access of the substrate to the C-domain active site. Moreover, in rat thoracic aorta BPP-BrachyNH2 induces potent endothelium-dependent vasodilatation with similar magnitude as captopril. In DAF-FM DA-loaded aortic cross sections examined by confocal microscopy, BPP-BrachyNH2 was found to increase the release of nitric oxide (NO). Moreover, BPP-BrachyNH2 was devoid of toxicity in endothelial and smooth muscle cell cultures. In conclusion, the peptide BPP-BrachyNH2 has a novel sequence being the first BPP isolated from the skin secretion of the Brachycephalidae family. This opens for exploring amphibians as a source of new biomolecules. The BPP-BrachyNH2 is devoid of cytotoxicity and elicits endothelium-dependent vasodilatation mediated by NO. These findings open for the possibility of potential application of these peptides in the treatment of endothelial dysfunction and cardiovascular diseases. PMID:26661890

  18. Supramolecular assemblies of histidinylated β-cyclodextrin for enhanced oligopeptide delivery into osteoclast precursors.

    PubMed

    Liu, Wei; Zhang, Xuejin; Wang, Rui; Xu, Hong; Chi, Bo

    2016-01-01

    Much attention has been given to the problem of drug delivery through the cell membrane in order to treat and manage bone diseases recently. The aim of this study was to develop nanoparticles made of amino- and histidinyl-modified amphiphilic β-cyclodextrins (β-CDs) entrapping osteoclast inhibitor, a hydrophobic oligopeptides drug, across the membrane of bone marrow-derived macrophages (BMMs). Drug-loaded β-CDs nanoparticles (NPs) were prepared by the emulsion solvent evaporation technique and fully characterized for size, zeta potential, and entrapment efficiency. Spherical NPs displaying a hydrodynamic radius of about 295 nm which did not change upon storage as an aqueous dispersion, a positive zeta potential, and entrapment efficiency of drug very close to 98% were produced. Flow cytometry and spectrofluorimetry analysis indicated that the model drug itself was not taken up by the BMMs; however, NP systems underwent significant cellular uptake. In particular, histidinyl group-modified CD (β-CD-H) NPs were taken up more efficiently than amino group-modified (β-CD-A) ones. Cellular uptake mechanism study demonstrated that the permeability of drug-loaded NPs across the membrane of BMMs is probably due to macropinocytosis pathway. Cell viability studies showed that both β-CD-A and β-CD-H exhibited no significant cytotoxicity up to 1.0 mg/ml against the cells. These results highlight the developed β-CD-H NPs have great potential in safely and effectively delivering osteoclast inhibitors and other therapeutic agents toward bone disease. PMID:26907470

  19. Redox activity and multiple copper(I) coordination of 2His-2Cys oligopeptide.

    PubMed

    Choi, DongWon; Alshahrani, Aisha A; Vytla, Yashodharani; Deeconda, Manogna; Serna, Victor J; Saenz, Robert F; Angel, Laurence A

    2015-02-01

    Copper binding motifs with their molecular mechanisms of selective copper(I) recognition are essential molecules for acquiring copper ions, trafficking copper to specific locations and controlling the potentially damaging redox activities of copper in biochemical processes. The redox activity and multiple Cu(I) binding of an analog methanobactin peptide-2 (amb2) with the sequence acetyl-His1-Cys2-Tyr3-Pro4-His5-Cys6 was investigated using ion mobility-mass spectrometry (IM-MS) and UV-Vis spectrophotometry analyses. The Cu(II) titration of amb2 showed oxidation of amb2 via the formation of intra- and intermolecular Cys-Cys disulfide bridges and the multiple Cu(I) coordination by unoxidized amb2 or the partially oxidized dimer and trimer of amb2. The principal product of these reactions was [amb2 + 3Cu(I)](+) which probably coordinates the three Cu(I) ions via two bridging thiolate groups of Cys2 and Cys6 and the δN6 of the imidazole groups of His6, as determined by geometry optimized structures at the B3LYP/LanL2DZ level of theory. The products observed by IM-MS showed direct correlation to spectral changes associated with disulfide bond formation in the UV-Vis spectrophotometric study. The results show that IM-MS analysis is a powerful technique for unambiguously determining the major ion species produced during the redox and metal binding chemistry of oligopeptides. PMID:25800013

  20. Meclofenamate elicits a nephropreventing effect in a rat model of ischemic acute kidney injury by suppressing indoxyl sulfate production and restoring renal organic anion transporters

    PubMed Central

    Saigo, Chika; Nomura, Yui; Yamamoto, Yuko; Sagata, Masataka; Matsunaga, Rika; Jono, Hirofumi; Nishi, Kazuhiko; Saito, Hideyuki

    2014-01-01

    Indoxyl sulfate (IS), a putative low-molecular weight uremic toxin, is excreted in the urine under normal kidney function, but is retained in the circulation and tissues during renal dysfunction in acute kidney injury and chronic kidney disease. IS, which is one of the most potent inducers of oxidative stress in the kidney and cardiovascular system, is enzymatically produced in the liver from indole by cytochrome P450-mediated hydroxylation to indoxyl, followed by sulfotransferase-mediated sulfate conjugation. We used rat liver S9 fraction to identify inhibitors of IS production. After testing several compounds, including phytochemical polyphenols, we identified meclofenamate as a potent inhibitor of IS production with an apparent IC50 value of 1.34 μM. Ischemia/reperfusion (I/R) of rat kidney caused a marked elevation in the serum IS concentration 48 hours after surgery. However, intravenous administration of meclofenamate (10 mg/kg) significantly suppressed this increase in the serum level of IS. Moreover, IS concentrations in both kidney and liver were dramatically elevated by renal I/R treatment, but this increase was blocked by meclofenamate. Serum creatinine and blood urea nitrogen were markedly elevated in rats after renal I/R treatment, but these increases were significantly restored by administration of meclofenamate. Renal expression of both basolateral membrane-localized organic anion transporters rOAT1 and rOAT3 was downregulated by I/R treatment. However, expression of rOAT1 and rOAT3 recovered after administration of meclofenamate, which is associated with the inhibition of I/R-evoked elevation of prostaglandin E2. Our results suggest that meclofenamate inhibits hepatic sulfotransferase-mediated production of IS, thereby suppressing serum and renal accumulation of IS. Meclofenamate also prevents the prostaglandin E2-dependent downregulation of rOAT1 and rOAT3 expression. In conclusion, meclofenamate was found to elicit a nephropreventive effect in

  1. Meclofenamate elicits a nephropreventing effect in a rat model of ischemic acute kidney injury by suppressing indoxyl sulfate production and restoring renal organic anion transporters.

    PubMed

    Saigo, Chika; Nomura, Yui; Yamamoto, Yuko; Sagata, Masataka; Matsunaga, Rika; Jono, Hirofumi; Nishi, Kazuhiko; Saito, Hideyuki

    2014-01-01

    Indoxyl sulfate (IS), a putative low-molecular weight uremic toxin, is excreted in the urine under normal kidney function, but is retained in the circulation and tissues during renal dysfunction in acute kidney injury and chronic kidney disease. IS, which is one of the most potent inducers of oxidative stress in the kidney and cardiovascular system, is enzymatically produced in the liver from indole by cytochrome P450-mediated hydroxylation to indoxyl, followed by sulfotransferase-mediated sulfate conjugation. We used rat liver S9 fraction to identify inhibitors of IS production. After testing several compounds, including phytochemical polyphenols, we identified meclofenamate as a potent inhibitor of IS production with an apparent IC50 value of 1.34 μM. Ischemia/reperfusion (I/R) of rat kidney caused a marked elevation in the serum IS concentration 48 hours after surgery. However, intravenous administration of meclofenamate (10 mg/kg) significantly suppressed this increase in the serum level of IS. Moreover, IS concentrations in both kidney and liver were dramatically elevated by renal I/R treatment, but this increase was blocked by meclofenamate. Serum creatinine and blood urea nitrogen were markedly elevated in rats after renal I/R treatment, but these increases were significantly restored by administration of meclofenamate. Renal expression of both basolateral membrane-localized organic anion transporters rOAT1 and rOAT3 was downregulated by I/R treatment. However, expression of rOAT1 and rOAT3 recovered after administration of meclofenamate, which is associated with the inhibition of I/R-evoked elevation of prostaglandin E2. Our results suggest that meclofenamate inhibits hepatic sulfotransferase-mediated production of IS, thereby suppressing serum and renal accumulation of IS. Meclofenamate also prevents the prostaglandin E2-dependent downregulation of rOAT1 and rOAT3 expression. In conclusion, meclofenamate was found to elicit a nephropreventive effect in

  2. The multicopy sRNA LhrC controls expression of the oligopeptide-binding protein OppA in Listeria monocytogenes.

    PubMed

    Sievers, Susanne; Lund, Anja; Menendez-Gil, Pilar; Nielsen, Aaraby; Storm Mollerup, Maria; Lambert Nielsen, Stine; Buch Larsson, Pernille; Borch-Jensen, Jonas; Johansson, Jörgen; Kallipolitis, Birgitte Haahr

    2015-01-01

    Listeria monocytogenes is the causative agent of the foodborne disease listeriosis. During infection, L. monocytogenes produces an array of non-coding RNAs, including the multicopy sRNA LhrC. These five, nearly identical sRNAs are highly induced in response to cell envelope stress and target the virulence adhesin lapB at the post-transcriptional level. Here, we demonstrate that LhrC controls expression of additional genes encoding cell envelope-associated proteins with virulence function. Using transcriptomics and proteomics, we identified a set of genes affected by LhrC in response to cell envelope stress. Three targets were significantly down-regulated by LhrC at both the RNA and protein level: lmo2349, tcsA and oppA. All three genes encode membrane-associated proteins: A putative substrate binding protein of an amino acid ABC transporter (Lmo2349); the CD4+ T cell-stimulating antigen TcsA, and the oligopeptide binding protein OppA, of which the latter 2 are required for full virulence of L. monocytogenes. For OppA, we show that LhrC acts by direct base paring to the ribosome binding site of the oppA mRNA, leading to an impediment of its translation and a decreased mRNA level. The sRNA-mRNA interaction depends on 2 of 3 CU-rich regions in LhrC allowing binding of 2 oppA mRNAs to a single LhrC molecule. Finally, we found that LhrC contributes to infection in macrophage-like cells. These findings demonstrate a central role for LhrC in controlling the level of OppA and other virulence-associated cell envelope proteins in response to cell envelope stress. PMID:26176322

  3. The multicopy sRNA LhrC controls expression of the oligopeptide-binding protein OppA in Listeria monocytogenes

    PubMed Central

    Sievers, Susanne; Lund, Anja; Menendez-Gil, Pilar; Nielsen, Aaraby; Storm Mollerup, Maria; Lambert Nielsen, Stine; Buch Larsson, Pernille; Borch-Jensen, Jonas; Johansson, Jörgen; Kallipolitis, Birgitte Haahr

    2015-01-01

    Listeria monocytogenes is the causative agent of the foodborne disease listeriosis. During infection, L. monocytogenes produces an array of non-coding RNAs, including the multicopy sRNA LhrC. These five, nearly identical sRNAs are highly induced in response to cell envelope stress and target the virulence adhesin lapB at the post-transcriptional level. Here, we demonstrate that LhrC controls expression of additional genes encoding cell envelope-associated proteins with virulence function. Using transcriptomics and proteomics, we identified a set of genes affected by LhrC in response to cell envelope stress. Three targets were significantly down-regulated by LhrC at both the RNA and protein level: lmo2349, tcsA and oppA. All three genes encode membrane-associated proteins: A putative substrate binding protein of an amino acid ABC transporter (Lmo2349); the CD4+ T cell-stimulating antigen TcsA, and the oligopeptide binding protein OppA, of which the latter 2 are required for full virulence of L. monocytogenes. For OppA, we show that LhrC acts by direct base paring to the ribosome binding site of the oppA mRNA, leading to an impediment of its translation and a decreased mRNA level. The sRNA-mRNA interaction depends on 2 of 3 CU-rich regions in LhrC allowing binding of 2 oppA mRNAs to a single LhrC molecule. Finally, we found that LhrC contributes to infection in macrophage-like cells. These findings demonstrate a central role for LhrC in controlling the level of OppA and other virulence-associated cell envelope proteins in response to cell envelope stress. PMID:26176322

  4. Binding capability of the enediyne-associated apoprotein to human tumors and constitution of a ligand oligopeptide-integrated protein.

    PubMed

    Cai, Lin; Chen, Hongxia; Miao, Qingfang; Wu, Shuying; Shang, Yue; Zhen, Yongsu

    2009-10-26

    The molecule of lidamycin that belongs to the chromoprotein family of antitumor antibiotics is composed of an apoprotein (LDP) and an enediyne chromophore. The enediyne moiety of the molecule is responsible for the potent cytotoxicity; however, the biological function of the apoprotein moiety, particularly its interaction with cancer cells, remains unclear. In present study, the binding capability of LDP to human tumors was detected for the first time by tissue microarray. LDP bound to various human tumors with significant difference from the corresponding normal tissues. Positive correlation between binding activity and the overexpression of VEGF and EGFR was confirmed by lung carcinoma tissue microarray. A fusion protein LG-LDP that consists of LDP and a ligand oligopeptide to EGFR was constructed by DNA recombination. LG-LDP showed augmented binding to EGFR-overexpressing cancer cells. Furthermore, an energized fusion protein LG-LDP-AE was prepared by integrating the active enediyne (AE) into LG-LDP molecule. By MTT assay, LG-LDP-AE displayed extremely potent cytotoxicity to cancer cells with IC50 approximate to 0.01nM. The results indicate that LDP binds to various human tumors and it might serve as a delivery carrier by integration of ligand oligopeptide to manufacture motif-based, targeted fusion proteins for cancer. PMID:19737585

  5. A genetic algorithm encoded with the structural information of amino acids and dipeptides for efficient conformational searches of oligopeptides.

    PubMed

    Ru, Xiao; Song, Ce; Lin, Zijing

    2016-05-15

    The genetic algorithm (GA) is an intelligent approach for finding minima in a highly dimensional parametric space. However, the success of GA searches for low energy conformations of biomolecules is rather limited so far. Herein an improved GA scheme is proposed for the conformational search of oligopeptides. A systematic analysis of the backbone dihedral angles of conformations of amino acids (AAs) and dipeptides is performed. The structural information is used to design a new encoding scheme to improve the efficiency of GA search. Local geometry optimizations based on the energy calculations by the density functional theory are employed to safeguard the quality and reliability of the GA structures. The GA scheme is applied to the conformational searches of Lys, Arg, Met-Gly, Lys-Gly, and Phe-Gly-Gly representative of AAs, dipeptides, and tripeptides with complicated side chains. Comparison with the best literature results shows that the new GA method is both highly efficient and reliable by providing the most complete set of the low energy conformations. Moreover, the computational cost of the GA method increases only moderately with the complexity of the molecule. The GA scheme is valuable for the study of the conformations and properties of oligopeptides. © 2016 Wiley Periodicals, Inc. PMID:26833761

  6. Holographic microscopy provides new insights into the settlement of zoospores of the green alga Ulva linza on cationic oligopeptide surfaces.

    PubMed

    Vater, Svenja M; Finlay, John; Callow, Maureen E; Callow, James A; Ederth, Thomas; Liedberg, Bo; Grunze, Michael; Rosenhahn, Axel

    2015-01-01

    Interaction of zoospores of Ulva linza with cationic, arginine-rich oligopeptide self-assembled monolayers (SAMs) is characterized by rapid settlement. Some spores settle (ie permanently attach) in a 'normal' manner involving the secretion of a permanent adhesive, retraction of the flagella and cell wall formation, whilst others undergo 'pseudosettlement' whereby motile spores are trapped (attached) on the SAM surface without undergoing the normal metamorphosis into a settled spore. Holographic microscopy was used to record videos of swimming zoospores in the vicinity of surfaces with different cationic oligopeptide concentrations to provide time-resolved insights into processes associated with attachment of spores. The data reveal that spore attachment rate increases with increasing cationic peptide content. Accordingly, the decrease in swimming activity in the volume of seawater above the surface accelerated with increasing surface charge. Three-dimensional trajectories of individual swimming spores showed a 'hit and stick' motion pattern, exclusively observed for the arginine-rich peptide SAMs, whereby spores were immediately trapped upon contact with the surface. PMID:25875964

  7. Effect of condensation agents and minerals for oligopeptide formation under mild and hydrothermal conditions in related to chemical evolution of proteins

    NASA Astrophysics Data System (ADS)

    Kawamura, Kunio; Takeya, Hitoshi; Kushibe, Takao

    2009-07-01

    The role of condensation agents and minerals for oligopeptide formation was inspected to see whether minerals possess catalytic activity under mild and hydrothermal conditions. Under mild conditions, oligopeptide formation from negatively charged amino acids (Asp and Glu) using different minerals and the elongation of alanine oligopeptides ((Ala) 2-(Ala) 5) were attempted using apatite minerals. Oligo(Asp) up to 10 amino acid units from Asp were observed in the presence of 1-ethyl-3-(3-dimethylaminopropyl carbodiimide (EDC). Notable influence of minerals was not detected for the oligo(Asp) formation. Oligo(Asp) was gradually degraded by the further incubation in the presence of EDC in both the absence and presence of minerals. The formation of oligo(Glu) was less efficient in the presence of carbonyldiimidazole. The elongation from (Ala) 3, (Ala) 4, and (Ala) 5 and the formation of diketopiperazine from (Ala) 2 proceeded immediately in the presence of EDC in the meantime of the sample preparations. In addition, it was unexpected that the disappearance of the products and the reformation of the reactants occurred by the further incubation for 24 h; for instance, (Ala) 5 decreased but (Ala) 4 increased with increasing the reaction time in the reaction of (Ala) 4 with EDC. These facts suggest that the activation of the reactant amino acids or peptides immediately occurs. Under the simulated hydrothermal conditions, EDC did not enhance the formation of oligopeptides from Asp, Glu or Ala nor the spontaneous formation of (Ala) 5 from (Ala) 4.

  8. Suppression Pattern of Neutral Pions at High Transverse Momentum in Au+Au Collisions at {radical}(s{sub NN})=200 GeV and Constraints on Medium Transport Coefficients

    SciTech Connect

    Adare, A.; Bickley, A. A.; Ellinghaus, F.; Kelly, S.; Kinney, E.; Nagle, J. L.; Seele, J.; Wysocki, M.; Afanasiev, S.; Isupov, A.; Litvinenko, A.; Malakhov, A.; Peresedov, V.; Rukoyatkin, P.; Zolin, L.; Aidala, C.; Bjorndal, M. T.; Chi, C. Y.; Cole, B. A.; D'Enterria, D.

    2008-12-05

    For Au+Au collisions at 200 GeV, we measure neutral pion production with good statistics for transverse momentum, p{sub T}, up to 20 GeV/c. A fivefold suppression is found, which is essentially constant for 5transport coefficient of the medium, e.g., in the parton quenching model. The spectral shape is similar for all collision classes, and the suppression does not saturate in Au+Au collisions.

  9. Fluorescent monitoring of copper-occupancy in His-ended catalytic oligo-peptides.

    PubMed

    Inokuchi, Reina; Kawano, Tomonori

    2016-01-01

    Controlled generation of reactive oxygen species (ROS) is widely beneficial to various medical, environmental, and agricultural studies. As inspired by the functional motifs in natural proteins, our group has been engaged in development of catalytically active oligo-peptides as minimum-sized metalloenzymes for generation of superoxide anion, an active member of ROS. In such candidate molecules, catalytically active metal-binding minimal motif was determined to be X-X-H, where X can be most amino acids followed by His. Based on above knowledge, we have designed a series of minimal copper-binding peptides designated as G n H series peptides, which are composed of oligo-glycyl chains ended with C-terminal His residue such as GGGGGH sequence (G5H). In order to further study the role of copper binding to the peptidic catalysts sharing the X-X-H motif such as G5H-conjugated peptides, we should be able to score the occupancy of the peptide population by copper ion in the reaction mixture. Here, model peptides with Cu-binding affinity which show intrinsic fluorescence due to tyrosyl residue (Y) in the UV region (excitation at ca. 230 and 280 nm, and emission at ca. 320 nm) were synthesized to score the effect of copper occupancy. Synthesized peptides include GFP-derived fluorophore sequence, TFSYGVQ (designated as Gfp), and Gfp sequence fused to C-terminal G5H (Gfp-G5H). In addition, two Y-containing tri-peptides derived from natural GFP fluorophores, namely, TYG and SYG were fused to the G5H (TYG-G5H and SYG-G5H). Conjugation of metal-binding G5H sequence to GFP-fluorophore peptide enhanced the action of Cu(2+) on quenching of intrinsic fluorescence due to Y residue. Two other Y-containing peptides, TYG-G5H and SYG-G5H, also showed intrinsic fluorescence which is sensitive to addition of Cu(2+). There was linear relationship between the loading of Cu(2+) and the quenching of fluorescence in these peptide, suggesting that Cu(2+)-dependent quenching of Y

  10. Fluorescent monitoring of copper-occupancy in His-ended catalytic oligo-peptides

    PubMed Central

    Inokuchi, Reina; Kawano, Tomonori

    2016-01-01

    ABSTRACT Controlled generation of reactive oxygen species (ROS) is widely beneficial to various medical, environmental, and agricultural studies. As inspired by the functional motifs in natural proteins, our group has been engaged in development of catalytically active oligo-peptides as minimum-sized metalloenzymes for generation of superoxide anion, an active member of ROS. In such candidate molecules, catalytically active metal-binding minimal motif was determined to be X-X-H, where X can be most amino acids followed by His. Based on above knowledge, we have designed a series of minimal copper-binding peptides designated as GnH series peptides, which are composed of oligo-glycyl chains ended with C-terminal His residue such as GGGGGH sequence (G5H). In order to further study the role of copper binding to the peptidic catalysts sharing the X-X-H motif such as G5H-conjugated peptides, we should be able to score the occupancy of the peptide population by copper ion in the reaction mixture. Here, model peptides with Cu-binding affinity which show intrinsic fluorescence due to tyrosyl residue (Y) in the UV region (excitation at ca. 230 and 280 nm, and emission at ca. 320 nm) were synthesized to score the effect of copper occupancy. Synthesized peptides include GFP-derived fluorophore sequence, TFSYGVQ (designated as Gfp), and Gfp sequence fused to C-terminal G5H (Gfp-G5H). In addition, two Y-containing tri-peptides derived from natural GFP fluorophores, namely, TYG and SYG were fused to the G5H (TYG-G5H and SYG-G5H). Conjugation of metal-binding G5H sequence to GFP-fluorophore peptide enhanced the action of Cu2+ on quenching of intrinsic fluorescence due to Y residue. Two other Y-containing peptides, TYG-G5H and SYG-G5H, also showed intrinsic fluorescence which is sensitive to addition of Cu2+. There was linear relationship between the loading of Cu2+ and the quenching of fluorescence in these peptide, suggesting that Cu2+-dependent quenching of Y

  11. Modification of ion transport in lipid bilayer membranes in the presence of 2,4-dichlorophenoxyacetic acid. II. Suppression of tetraphenylborate conductance and changes of interfacial potentials.

    PubMed Central

    Smejtek, P; Paulis-Illangasekare, M

    1979-01-01

    It has been shown that the blocking of negatively charged tetraphenylborate ion transport in phosphatidylcholine (PC)-cholesterol membranes by the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is dominated by suppression of TPhB- diffusion across the membrane interior, rather than by the decrease of adsorption of TPhB- ions at the membrane surface. The blocking effect can be associated with the decrease of electric potential inside the membrane with respect to that of the aqueous medium, this decreases being proportional to the concentration of 2,4-D in the aqueous solution. It has been estimated that 25 - 30% of the total 2,4-D-induced change of the potential difference is between the plane of absorption of TPhB- and the aqueous solution, and the remaining fraction is between the membrane interior and the absorption plane. The results of this study support the dipolar hypothesis of 2,4-D action in lipid membranes. These conclusions are further supported by measurements changes of electric potential difference across air/water and air/lipid monolayer/water interfaces. It has been found that the electric potential of the nonpolar side of the interface decreases in the presence of neutral molecules of 2,4-D and that this effect becomes more prominent in presence of electrolyte. We have confirmed that PC-cholesterol monolayer cannot be considered as a model for half of the bilayer membrane because of the disagreement between the changes of the interfacial potential difference of PC-cholesterol monolayers and those determined from studied of transport of positive and negative ions across bilayer membranes. In contract, we have found close agreement between the 2,4-D-induced changes of electric potential of the lipid hydrocarbon region in glycerolmonooleate (GMO) membranes and GMO monolayers. We suggest that the action of 2,4-D in lipid membranes is not associated with the changes of orientation of dipoles of lipids constituting the membranes, but rather with a layer

  12. Modification of ion transport in lipid bilayer membranes in the presence of 2,4-dichlorophenoxyacetic acid. II. Suppression of tetraphenylborate conductance and changes of interfacial potentials.

    PubMed

    Smejtek, P; Paulis-Illangasekare, M

    1979-06-01

    It has been shown that the blocking of negatively charged tetraphenylborate ion transport in phosphatidylcholine (PC)-cholesterol membranes by the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is dominated by suppression of TPhB- diffusion across the membrane interior, rather than by the decrease of adsorption of TPhB- ions at the membrane surface. The blocking effect can be associated with the decrease of electric potential inside the membrane with respect to that of the aqueous medium, this decreases being proportional to the concentration of 2,4-D in the aqueous solution. It has been estimated that 25 - 30% of the total 2,4-D-induced change of the potential difference is between the plane of absorption of TPhB- and the aqueous solution, and the remaining fraction is between the membrane interior and the absorption plane. The results of this study support the dipolar hypothesis of 2,4-D action in lipid membranes. These conclusions are further supported by measurements changes of electric potential difference across air/water and air/lipid monolayer/water interfaces. It has been found that the electric potential of the nonpolar side of the interface decreases in the presence of neutral molecules of 2,4-D and that this effect becomes more prominent in presence of electrolyte. We have confirmed that PC-cholesterol monolayer cannot be considered as a model for half of the bilayer membrane because of the disagreement between the changes of the interfacial potential difference of PC-cholesterol monolayers and those determined from studied of transport of positive and negative ions across bilayer membranes. In contract, we have found close agreement between the 2,4-D-induced changes of electric potential of the lipid hydrocarbon region in glycerolmonooleate (GMO) membranes and GMO monolayers. We suggest that the action of 2,4-D in lipid membranes is not associated with the changes of orientation of dipoles of lipids constituting the membranes, but rather with a layer

  13. Transportation.

    ERIC Educational Resources Information Center

    Crank, Ron

    This instructional unit is one of 10 developed by students on various energy-related areas that deals specifically with transportation and energy use. Its objective is for the student to be able to discuss the implication of energy usage as it applies to the area of transportation. Some topics covered are efficiencies of various transportation…

  14. Separation of basic oligopeptides by ion-pairing reversed-phase chromatography

    NASA Astrophysics Data System (ADS)

    Xie, Wenchun

    The present thesis consist of five chapters. Chapter I introduces background information on the ion-pairing reversed-phase chromatography and liquid chromatography in the critical condition. Chapter II decribes our study on the isocratic separation of oligolysine (dp = 2 to 8) using a fixed content of acetonitrile (ACN) (23%) and different concentrations of HFBA in the mobile phase (0.6-30.6 mM) on a Waters XBridge Shield RP18® column. We found that the retention time of oligolysine increases as the dp increases, because of an increased number of HFBA bound to the peptides. Furthermore, when [HFBA] increased, the retention time increased at different rates. The greater the dp, the faster the rate. Based on a closed pairing model that presumes an equilibrium between an unpaired state and the paired state with a fixed number of HFBA molecules, an equation was derived for the retention factor of oligolysine. In Chapter III, we compare retention behaviors of oligolysine (dp = 2 to 8) and oligoarginine (dp = 2 to 8) when they are separated on the Waters XBridge Shield RP18® using fixed a ACN content (23%) and difference concentrations of HFBA (0.4-30.6 mM) in the mobile phase. The retention time of oligoarginine also increased at different rates as [HFBA] increased. The greater the dp, the faster the rate. The retention time of oligolysine is shorter than that of oligarginine having the dame dp. We applied Eq.1 to analyze the plot of ln k as a function of [HFBA] for each oligopeptide component to obtain the values for n, Kip,m, and βKd,ip. For oligolysine, n increases linearly as dp increase and oligoarginine exhibits an accelerated increase in n as dp rises. The plot of ln βKd,ip against dp followed a linear relationship for both peptides. In Chapter IV, we study the effect of mobile phase composition on the retention of oligolysine (dp = 2 to 8) on the Waters XBridge Shield RP18 ®. The ACN content was changed from 20% to 33% and the HFBA concentration from 0.7 to

  15. Jet Noise Suppression

    NASA Technical Reports Server (NTRS)

    Gliebe, P. R.; Brausch, J. F.; Majjigi, R. K.; Lee, R.

    1991-01-01

    The objectives of this chapter are to review and summarize the jet noise suppression technology, to provide a physical and theoretical model to explain the measured jet noise suppression characteristics of different concepts, and to provide a set of guidelines for evolving jet noise suppression designs. The underlying principle for all jet noise suppression devices is to enhance rapid mixing (i.e., diffusion) of the jet plume by geometric and aerothermodynamic means. In the case of supersonic jets, the shock-cell broadband noise reduction is effectively accomplished by the elimination or mitigation of the shock-cell structure. So far, the diffusion concepts have predominantly concentrated on jet momentum and energy (kinetic and thermal) diffusion, in that order, and have yielded better noise reduction than the simple conical nozzles. A critical technology issue that needs resolution is the effect of flight on the noise suppression potential of mechanical suppressor nozzles. A more thorough investigation of this mechanism is necessary for the successful development and design of an acceptable noise suppression device for future high-speed civil transports.

  16. Photospintronics: Magnetic Field-Controlled Photoemission and Light-Controlled Spin Transport in Hybrid Chiral Oligopeptide-Nanoparticle Structures

    PubMed Central

    2016-01-01

    The combination of photonics and spintronics opens new ways to transfer and process information. It is shown here that in systems in which organic molecules and semiconductor nanoparticles are combined, matching these technologies results in interesting new phenomena. We report on light induced and spin-dependent charge transfer process through helical oligopeptide–CdSe nanoparticles’ (NPs) architectures deposited on ferromagnetic substrates with small coercive force (∼100–200 Oe). The spin control is achieved by the application of the chirality-induced spin-dependent electron transfer effect and is probed by two different methods: spin-controlled electrochemichemistry and photoluminescence (PL) at room temperature. The injected spin could be controlled by excitation of the nanoparticles. By switching the direction of the magnetic field of the substrate, the PL intensity could be alternated. PMID:27027885

  17. Homochiral oligopeptides via surface recognition and enantiomeric cross impediment in the polymerization of racemic phenylalanine N-carboxyanhydride crystals suspended in water.

    PubMed

    Nery, Jose Geraldo; Eliash, Ran; Bolbach, Gerard; Weissbuch, Isabelle; Lahav, Meir

    2007-08-01

    As part of our program on the search of possible prebiotic routes for the formation of oligopeptides of homochiral sequence (isotactic) from racemic precursors in aqueous environment, we report the polymerization of racemic crystals of phenylalanine N-carboxyanhydrides, enantioselectively tagged with five deuterium atoms, suspended in water containing various amine initiators. Racemic mixtures of isotactic oligopeptides, comprising up to 25 repeat units of the same handedness, as the dominant component for each length, were observed in a MALDI-TOF mass spectrometry analysis. The racemic mixtures of the peptides could be desymmetrized by initiating the polymerization reaction with water-soluble methyl esters of either enantiopure alpha-amino acids or dipeptides. A three-step mechanism is proposed to account for these results: (i) Surface recognition of the chiral initiator by the chiral sites present at specific faces of the crystal; (ii) Oligopeptide elongation at the polymer/crystal interface; and (iii) Self-assembly of the short isotactic peptides into racemic antiparallel beta-sheets as templates followed by cross-enantiomeric impediment in the growth of enantiomeric chains at the peptide beta-sheet/crystal interface. PMID:17354263

  18. Multiple Sites of the Cleavage of 21- and 25-Mer Encephalytogenic Oligopeptides Corresponding to Human Myelin Basic Protein (MBP) by Specific Anti-MBP Antibodies from Patients with Systemic Lupus Erythematosus

    PubMed Central

    Timofeeva, Anna M.; Dmitrenok, Pavel S.; Konenkova, Ludmila P.; Buneva, Valentina N.; Nevinsky, Georgy A.

    2013-01-01

    IgGs from patients with multiple sclerosis and systemic lupus erythematosus (SLE) purified on MBP-Sepharose in contrast to canonical proteases hydrolyze effectively only myelin basic protein (MBP), but not many other tested proteins. Here we have shown for the first time that anti-MBP SLE IgGs hydrolyze nonspecific tri- and tetrapeptides with an extreme low efficiency and cannot effectively hydrolyze longer 20-mer nonspecific oligopeptides corresponding to antigenic determinants (AGDs) of HIV-1 integrase. At the same time, anti-MBP SLE IgGs efficiently hydrolyze oligopeptides corresponding to AGDs of MBP. All sites of IgG-mediated proteolysis of 21-and 25-mer encephalytogenic oligopeptides corresponding to two known AGDs of MBP were found by a combination of reverse-phase chromatography, TLC, and MALDI spectrometry. Several clustered major, moderate, and minor sites of cleavage were revealed in the case of 21- and 25-mer oligopeptides. The active sites of anti-MBP abzymes are localised on their light chains, while heavy chains are responsible for the affinity of protein substrates. Interactions of intact globular proteins with both light and heavy chains of abzymes provide high affinity to MBP and specificity of this protein hydrolysis. The affinity of anti-MBP abzymes for intact MBP is approximately 1000-fold higher than for the oligopeptides. The data suggest that all oligopeptides interact mainly with the light chains of different monoclonal abzymes of total pool of IgGs, which possesses a lower affinity for substrates, and therefore, depending on the oligopeptide sequences, their hydrolysis may be less specific than globular protein and can occur in several sites. PMID:23520443

  19. Studies of Transport Properties and Critical Temperature Suppression Mechanism in Yttrium BARIUM(2) COPPER(3) Oxygen(x) Thin Films Irradiated with 20 TO 120 KEV Electrons

    NASA Astrophysics Data System (ADS)

    Lin, Jiunn-Yuan

    1995-11-01

    We present comprehensive studies of the effects of 20 to 120 keV electron irradiation on rm YBa_2Cu_3O_{x} thin films. Above 60 keV, T_{c } of irradiated samples is suppressed accompanied by a significant increase in residual resistivity, while the carrier concentration remains relatively unchanged. The plane oxygen defects produced by irradiation are found to be responsible for T_{c} suppression. The II suppression mechanism is discussed within several theoretical frameworks. Though in qualitative agreement with d-wave pairing symmetry, our results show a T_{c} suppression rate three times as slow as predicted by the theory when resistivity data are used to extract the impurity scattering rate. Alternatively, phase fluctuations theory gives a qualitative description as well. The displacement energy of plane oxygen is found to be 8.3 eV, which corresponds to a threshold electron energy 58 keV. Finally, an empirical relation is proposed to describe the temperature dependence of the Hall coefficient.

  20. Sea cucumber (Codonopsis pilosula) oligopeptides: immunomodulatory effects based on stimulating Th cells, cytokine secretion and antibody production.

    PubMed

    He, Li-Xia; Zhang, Zhao-Feng; Sun, Bin; Chen, Qi-He; Liu, Rui; Ren, Jin-Wei; Wang, Jun-Bo; Li, Yong

    2016-02-01

    This study aimed to investigate the immunomodulating activity of small molecule oligopeptides from sea cucumber (Codonopsis pilosula) (SOP) in mice. Seven assays were performed to determine the immunomodulatory effects, including splenic lymphocyte proliferation and delayed-type hypersensitivity assays (cell-mediated immunity), IgM antibody response of spleen to sheep red blood cells (SRBC) and serum hemolysin level assays (humoral immunity), the carbon clearance assay and the phagocytic capacity of peritoneal cavity phagocytes assay (macrophage phagocytosis), and the NK cell activity assay. Spleen T lymphocyte subpopulations, multiplex sandwich immunoassays of serum cytokine and immunoglobulin levels and enzyme-linked immunosorbent assays for small intestinal secretory immunoglobulin were performed to study the mechanism by which SOP affects the immune system. We found that SOP could improve immune functions in mice, which may be due to the enhancement of the functions of cell-mediated immunity, humoral immunity, macrophage phagocytosis and NK cell activity. From the cellular and molecular assays, we postulated that the immunomodulatory effects are most likely attributed to the stimulation of Th cells, cytokine secretion and antibody production. PMID:26838796

  1. P2X7 Receptor Activation Impairs Exogenous MHC Class I Oligopeptides Presentation in Antigen Presenting Cells

    PubMed Central

    Baroja-Mazo, Alberto; Barberà-Cremades, Maria; Pelegrín, Pablo

    2013-01-01

    Major histocompatibility complex class I (MHC I) on antigen presenting cells (APCs) is a potent molecule to activate CD8+ T cells and initiate immunity. P2X7 receptors (P2X7Rs) are present on the plasma membrane of APCs to sense the extracellular danger signal adenosine-5′-triphosphate (ATP). P2X7R activates the inflammasome and the release of IL-1β in macrophages and other immune cells to initiate the inflammatory response. Here we show that P2X7R stimulation by ATP in APCs decreased the amount of MHC I at the plasma membrane. Specific antagonism or genetic ablation of P2X7R inhibited the effects of ATP on levels of cellular MHC I. Furthermore, P2X7R stimulation was able to inhibit activation of CD8+ T cells via specific MHC I-oligopeptide complexes. Our study suggests that P2X7R activation on APCs is a novel inhibitor of adaptive CD8+ T cell immunity. PMID:23940597

  2. P2X7 receptor activation impairs exogenous MHC class I oligopeptides presentation in antigen presenting cells.

    PubMed

    Baroja-Mazo, Alberto; Barberà-Cremades, Maria; Pelegrín, Pablo

    2013-01-01

    Major histocompatibility complex class I (MHC I) on antigen presenting cells (APCs) is a potent molecule to activate CD8(+) T cells and initiate immunity. P2X7 receptors (P2X7Rs) are present on the plasma membrane of APCs to sense the extracellular danger signal adenosine-5'-triphosphate (ATP). P2X7R activates the inflammasome and the release of IL-1β in macrophages and other immune cells to initiate the inflammatory response. Here we show that P2X7R stimulation by ATP in APCs decreased the amount of MHC I at the plasma membrane. Specific antagonism or genetic ablation of P2X7R inhibited the effects of ATP on levels of cellular MHC I. Furthermore, P2X7R stimulation was able to inhibit activation of CD8(+) T cells via specific MHC I-oligopeptide complexes. Our study suggests that P2X7R activation on APCs is a novel inhibitor of adaptive CD8(+) T cell immunity. PMID:23940597

  3. Calculation of Relative Binding Free Energy in the Water-Filled Active Site of Oligopeptide-Binding Protein A.

    PubMed

    Maurer, Manuela; de Beer, Stephanie B A; Oostenbrink, Chris

    2016-01-01

    The periplasmic oligopeptide binding protein A (OppA) represents a well-known example of water-mediated protein-ligand interactions. Here, we perform free-energy calculations for three different ligands binding to OppA, using a thermodynamic integration approach. The tripeptide ligands share a high structural similarity (all have the sequence KXK), but their experimentally-determined binding free energies differ remarkably. Thermodynamic cycles were constructed for the ligands, and simulations conducted in the bound and (freely solvated) unbound states. In the unbound state, it was observed that the difference in conformational freedom between alanine and glycine leads to a surprisingly slow convergence, despite their chemical similarity. This could be overcome by increasing the softness parameter during alchemical transformations. Discrepancies remained in the bound state however, when comparing independent simulations of the three ligands. These difficulties could be traced to a slow relaxation of the water network within the active site. Fluctuations in the number of water molecules residing in the binding cavity occur mostly on a timescale larger than the simulation time along the alchemical path. After extensive simulations, relative binding free energies that were converged to within thermal noise could be obtained, which agree well with available experimental data. PMID:27092480

  4. Influence of Free Amino Acids, Oligopeptides, and Polypeptides on the Formation of Pyrazines in Maillard Model Systems.

    PubMed

    Scalone, Gustavo Luis Leonardo; Cucu, Tatiana; De Kimpe, Norbert; De Meulenaer, Bruno

    2015-06-10

    Pyrazines are specific Maillard reaction compounds known to contribute to the unique aroma of many products. Most studies concerning the generation of pyrazines in the Maillard reaction have focused on amino acids, while little information is available on the impact of peptides and proteins. The present study investigated the generation of pyrazines in model systems containing whey protein, hydrolyzed whey protein, amino acids, and glucose. The impact of thermal conditions, ratio of reagents, and water activity (a(w)) on pyrazine formation was measured by headspace solid-phase microextraction with gas chromatography/mass spectrometry (HS-SPME-GC/MS. The presence of oligopeptides from hydrolyzed whey protein contributed significantly to an increased amount of pyrazines, while in contrast free amino acids generated during protein hydrolysis contributed to a lesser extent. The generation of pyrazines was enhanced at low a(w) (0.33) and high temperatures (>120 °C). This study showed that the role of peptides in the generation of pyrazines in Maillard reaction systems has been dramatically underestimated. PMID:25971942

  5. Multi-responsive Hydrogels Derived from the Self-assembly of Tethered Allyl-functionalized Racemic Oligopeptides

    PubMed Central

    He, Xun; Fan, Jingwei; Zhang, Fuwu; Li, Richen; Pollack, Kevin A.; Raymond, Jeffery E.; Zou, Jiong; Wooley, Karen L.

    2014-01-01

    A multi-responsive triblock hydrogelator oligo(dl-allylglycine)-block-poly(ethylene glycol)-block-oligo(dl-allylglycine) (ODLAG-b-PEG-b-ODLAG) was synthesized facilely by ring-opening polymerization (ROP) of DLAG N-carboxyanhydride (NCA) with a diamino-terminated PEG as the macroinitiator. This system exhibited heat-induced sol-to-gel transitions and either sonication- or enzyme-induced gel-to-sol transitions. The β-sheeting of the oligopeptide segments was confirmed by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and wide-angle X-ray scattering (WAXS). The β-sheets further displayed tertiary ordering into fibrillar structures that, in turn generated a porous and interconnected hydrogel matrix, as observed via transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The reversible macroscopic sol-to-gel transitions triggered by heat and gel-to-sol transitions triggered by sonication were correlated with the transformation of nanostructural morphologies, with fibrillar structures observed in gel and spherical aggregates in sol, respectively. The enzymatic breakdown of the hydrogels was also investigated. This allyl-functionalized hydrogelator can serve as a platform for the design of smart hydrogels, appropriate for expansion into biological systems as bio-functional and bio-responsive materials. PMID:25485113

  6. Quantitative constraints on the transport properties of hot partonic matter from semi-inclusive single high transverse momentum pion suppression in Au+Au collisions at {radical}(s{sub NN})=200 GeV

    SciTech Connect

    Adare, A.; Bickley, A. A.; Ellinghaus, F.; Kelly, S.; Kinney, E.; Nagle, J. L.; Seele, J.; Wysocki, M.; Afanasiev, S.; Isupov, A.; Litvinenko, A.; Malakhov, A.; Peresedov, V.; Rukoyatkin, P.; Zolin, L.; Aidala, C.; Bjorndal, M. T.; Chi, C. Y.; Cole, B. A.; D'Enterria, D.

    2008-06-15

    The PHENIX experiment has measured the suppression of semi-inclusive single high-transverse-momentum {pi}{sup 0}'s in Au+Au collisions at {radical}(s{sub NN})=200 GeV. The present understanding of this suppression is in terms of energy loss of the parent (fragmenting) parton in a dense color-charge medium. We have performed a quantitative comparison between various parton energy-loss models and our experimental data. The statistical point-to-point uncorrelated as well as correlated systematic uncertainties are taken into account in the comparison. We detail this methodology and the resulting constraint on the model parameters, such as the initial color-charge density dN{sup g}/dy, the medium transport coefficient , or the initial energy-loss parameter {epsilon}{sub 0}. We find that high-transverse-momentum {pi}{sup 0} suppression in Au+Au collisions has sufficient precision to constrain these model-dependent parameters at the {+-}20-25% (one standard deviation) level. These constraints include only the experimental uncertainties, and further studies are needed to compute the corresponding theoretical uncertainties.

  7. Preliminary evaluation of turbofan cycle parameters and acoustical suppression on the noise and direct operating cost of a commercial Mach 0.85 transport

    NASA Technical Reports Server (NTRS)

    Eisenberg, J. D.

    1975-01-01

    A study was made of the effects of turbofan cycle parameters and the use of acoustic noise suppression material to quiet 200 passenger, Mach 0.85 trijets having design ranges of 2778, 4630, and 9260 kilometers (1500, 2500, and 5000 n. mi). Aircraft gross weight and direct operating cost, which varied with amount of suppression and cycle selection, are presented as functions of both EPNdB traded and 90 EPNdB contour footprint area. Noise levels 10.9 EPNdB below FAR 36 requirements result in a 5 percent increase in DOC for an aircraft designed for a range of 9260 kilometers (5000 n. mi.). An aircraft designed for a 2778 kilometer (1500 n. mi.) range would have an EPNdB level 14 below FAR 36 for this same economic penalty. In this range of noise level, fan-machinery noise is the principal source.

  8. Three-dimensional equilibria and island energy transport due to resonant magnetic perturbation edge localized mode suppression on DIII-D

    NASA Astrophysics Data System (ADS)

    King, J. D.; Strait, E. J.; Nazikian, R.; Paz-Soldan, C.; Eldon, D.; Fenstermacher, M. E.; Ferraro, N. M.; Hanson, J. M.; Haskey, S. R.; La Haye, R. J.; Lanctot, M. J.; Lazerson, S. A.; Logan, N. C.; Liu, Y. Q.; Okabayashi, M.; Park, J.-K.; Shiraki, D.; Turnbull, A. D.

    2015-11-01

    Experiments in the DIII-D tokamak show that the plasma responds to resonant magnetic perturbations (RMPs) with toroidal mode numbers of n = 2 and n = 3 without field line reconnection, consistent with resistive magnetohydrodynamic predictions, while a strong nonlinear bifurcation is apparent when edge localized modes (ELMs) are suppressed. The magnetic response associated with this bifurcation is localized to the high field side of the machine and exhibits a dominant n = 1 component despite the application of a constant amplitude, slowly toroidally rotating, n = 2 applied field. The n = 1 mode is born locked to the vacuum vessel wall, while the n = 2 mode is entrained to the rotating field. Based on these magnetic response measurements and Thomson scattering measurements of flattening of the electron temperature profile, it is likely that these modes are magnetic island chains near the H-mode pedestal. The reduction in ∇Te occurs near the q = 4 and 5 rational surfaces, suggesting five unique islands are possible (m = 8, 9, or 10 for n = 2) and (m = 4 or 5 for n = 1). In all cases, the island width is estimated to be 2-3 cm. The Chang-Callen calculated confinement degradation due to the presence of an individual island of this size is 8%-12%, which is close to the 13%-14% measured between the ELMs and suppressed states. This suggests that edge tearing modes may alter the pedestal causing peeling-ballooning stability during RMP induced ELM suppression.

  9. Suppression of c-Myc is involved in multi-walled carbon nanotubes' down-regulation of ATP-binding cassette transporters in human colon adenocarcinoma cells

    SciTech Connect

    Wang, Zhaojing; Xu, Yonghong; Meng, Xiangning; Watari, Fumio; Liu, Hudan; Chen, Xiao

    2015-01-01

    Over-expression of ATP-binding cassette (ABC) transporters, a large family of integral membrane proteins that decrease cellular drug uptake and accumulation by active extrusion, is one of the major causes of cancer multi-drug resistance (MDR) that frequently leads to failure of chemotherapy. Carbon nanotubes (CNTs)-based drug delivery devices hold great promise in enhancing the efficacy of cancer chemotherapy. However, CNTs' effects on the ABC transporters remain under-investigated. In this study, we found that multiwalled carbon nanotubes (MWCNTs) reduced transport activity and expression of ABC transporters including ABCB1/Pgp and ABCC4/MRP4 in human colon adenocarcinoma Caco-2 cells. Proto-oncogene c-Myc, which directly regulates ABC gene expression, was concurrently decreased in MWCNT-treated cells and forced over-expression of c-Myc reversed MWCNTs' inhibitory effects on ABCB1 and ABCC4 expression. MWCNT-cell membrane interaction and cell membrane oxidative damage were observed. However, antioxidants such as vitamin C, β-mecaptoethanol and dimethylthiourea failed to antagonize MWCNTs' down-regulation of ABC transporters. These data suggest that MWCNTs may act on c-Myc, but not through oxidative stress, to down-regulate ABC transporter expression. Our findings thus shed light on CNTs' novel cellular effects that may be utilized to develop CNTs-based drug delivery devices to overcome ABC transporter-mediated cancer chemoresistance.

  10. Three-dimensional equilibria and island energy transport due to resonant magnetic perturbation edge localized mode suppression on DIII-D

    SciTech Connect

    King, J. D.; Strait, E. J.; Nazikian, R.; Paz-Soldan, Carlos; Eldon, D.; Fenstermacher, M. E.; Ferraro, N. M.; Hanson, J. M.; Haskey, S. R.; La Haye, R. J.; Lanctot, Matthew J.; Lazerson, Sam A.; Logan, N. C.; Liu, Y. Q.; Okabayashi, M.; Park, J. -K.; Turnbull, A. D.

    2015-11-16

    In this research, we conducted experiments in the DIII-D tokamak that show that the plasma responds to resonant magnetic perturbations (RMPs) with toroidalmode numbers of n=2 and n=3 without field line reconnection, consistent with resistive magnetohydrodynamic predictions, while a strong nonlinear bifurcation is apparent when edge localized modes(ELMs) are suppressed. The magnetic response associated with this bifurcation is localized to the high field side of the machine and exhibits a dominant n=1 component despite the application of a constant amplitude, slowly toroidally rotating, n=2 applied field. The n=1 mode is born locked to the vacuum vessel wall, while the n=2 mode is entrained to the rotating field. Based on these magnetic response measurements and Thomson scattering measurements of flattening of the electron temperature profile, it is likely that these modes are magnetic island chains near the H-mode pedestal. The reduction in ∇Te occurs near the q=4 and 5 rational surfaces, suggesting five unique islands are possible (m=8, 9, or 10 for n=2) and (m=4 or 5 for n=1). In all cases, the island width is estimated to be 2–3 cm. The Chang-Callen calculated confinement degradation due to the presence of an individual island of this size is 8%–12%, which is close to the 13%–14% measured between the ELMs and suppressed states. In conclusion, this suggests that edge tearing modes may alter the pedestal causing peeling-ballooning stability during RMP induced ELM suppression.

  11. Three-dimensional equilibria and island energy transport due to resonant magnetic perturbation edge localized mode suppression on DIII-D

    DOE PAGESBeta

    King, J. D.; Strait, E. J.; Nazikian, R.; Paz-Soldan, Carlos; Eldon, D.; Fenstermacher, M. E.; Ferraro, N. M.; Hanson, J. M.; Haskey, S. R.; La Haye, R. J.; et al

    2015-11-16

    In this research, we conducted experiments in the DIII-D tokamak that show that the plasma responds to resonant magnetic perturbations (RMPs) with toroidalmode numbers of n=2 and n=3 without field line reconnection, consistent with resistive magnetohydrodynamic predictions, while a strong nonlinear bifurcation is apparent when edge localized modes(ELMs) are suppressed. The magnetic response associated with this bifurcation is localized to the high field side of the machine and exhibits a dominant n=1 component despite the application of a constant amplitude, slowly toroidally rotating, n=2 applied field. The n=1 mode is born locked to the vacuum vessel wall, while the n=2more » mode is entrained to the rotating field. Based on these magnetic response measurements and Thomson scattering measurements of flattening of the electron temperature profile, it is likely that these modes are magnetic island chains near the H-mode pedestal. The reduction in ∇Te occurs near the q=4 and 5 rational surfaces, suggesting five unique islands are possible (m=8, 9, or 10 for n=2) and (m=4 or 5 for n=1). In all cases, the island width is estimated to be 2–3 cm. The Chang-Callen calculated confinement degradation due to the presence of an individual island of this size is 8%–12%, which is close to the 13%–14% measured between the ELMs and suppressed states. In conclusion, this suggests that edge tearing modes may alter the pedestal causing peeling-ballooning stability during RMP induced ELM suppression.« less

  12. Specific oligopeptides in fermented soybean extract inhibit NF-κB-dependent iNOS and cytokine induction by toll-like receptor ligands.

    PubMed

    Lee, Woo Hyung; Wu, Hong Min; Lee, Chan Gyu; Sung, Dae Il; Song, Hye Jung; Matsui, Toshiro; Kim, Han Bok; Kim, Sang Geon

    2014-11-01

    The ethanol extract of fermented soybean from Glycine max (chungkookjang, CHU) has been claimed to have chemopreventive and cytoprotective effects. In the present study, we examined the inhibitory effect of CHU on inducible nitric oxide synthase (iNOS) and cytokine induction by toll-like receptor (TLR) ligands treatment and attempted to identify the responsible active components. Nitric oxide (NO) content and iNOS levels in the media or RAW264.7 cells were measured using the Griess reagent and real-time polymerase chain reaction assays. CHU treatment inhibited NO production and iNOS induction elicited by lipopolysaccharide (LPS, TLR4L) in a concentration-dependent manner. Tumor necrosis factor-α and interleukin-6 productions were also diminished. Peptidoglycans (TLR2/6L) and CpG-oligodeoxynucleotides (TLR9L) from CHU inhibited iNOS induction, but not poly I:C (TLR3L) or loxoribine (TLF7L). The anti-inflammatory effect resulted from the inhibition of nuclear factor-kappa B (NF-κB) through the inhibition of inhibitory-κB degradation. Of the representative components in CHU, specific oligopeptides (AFPG and GVAWWMY) had the ability to inhibit iNOS induction by LPS, whereas others failed to do so. Daidzein, an isoflavone used for comparative purposes, was active at a relatively higher concentration. In an animal model, oral administration of CHU to rats significantly diminished carrageenan-induced paw edema and iNOS induction. Our results demonstrate that CHU has anti-inflammatory effects against TLR ligands by inhibiting NF-κB activation, which may result from specific oligopeptide components in CHU. Since CHU is orally effective, dietary applications of CHU and/or the identified oligopeptides may be of use in the prevention of inflammatory diseases. PMID:25184943

  13. Histidine-Rich Oligopeptides To Lessen Copper-Mediated Amyloid-β Toxicity.

    PubMed

    Caballero, Ana B; Terol-Ordaz, Laia; Espargaró, Alba; Vázquez, Guillem; Nicolás, Ernesto; Sabaté, Raimon; Gamez, Patrick

    2016-05-17

    Brain copper imbalance plays an important role in amyloid-β aggregation, tau hyperphosphorylation, and neurotoxicity observed in Alzheimer's disease (AD). Therefore, the administration of biocompatible metal-binding agents may offer a potential therapeutic solution to target mislocalized copper ions and restore metallostasis. Histidine-containing peptides and proteins are excellent metal binders and are found in many natural systems. The design of short peptides showing optimal binding properties represents a promising approach to capture and redistribute mislocalized metal ions, mainly due to their biocompatibility, ease of synthesis, and the possibility of fine-tuning their metal-binding affinities in order to suppress unwanted competitive binding with copper-containing proteins. In the present study, three peptides, namely HWH, HK(C) H, and HAH, have been designed with the objective of reducing copper toxicity in AD. These tripeptides form highly stable albumin-like complexes, showing higher affinity for Cu(II) than that of Aβ(1-40). Furthermore, HWH, HK(C) H, and HAH act as very efficient inhibitors of copper-mediated reactive oxygen species (ROS) generation and prevent the copper-induced overproduction of toxic oligomers in the initial steps of amyloid aggregation in the presence of Cu(II) ions. These tripeptides, and more generally small peptides including the sequence His-Xaa-His at the N-terminus, may therefore be considered as promising motifs for the future development of new and efficient anti-Alzheimer drugs. PMID:27071336

  14. XPS investigation on the structure of two dipeptides studied as models of self-assembling oligopeptides: comparison between experiments and theory

    NASA Astrophysics Data System (ADS)

    Battocchio, C.; Iucci, G.; Dettin, M.; Monti, S.; Carravetta, V.; Polzonetti, G.

    2008-03-01

    The adsorption on TiO2 surface of two dipeptides AE (L-alanine-L-glutamic acid) and AK (L-alanine-L-lysine), that are 'building blocks' of the more complex self-complementary amphiphilic oligopeptides and are therefore a good model in the interpretation of the complex peptide spectra, has been investigated both theoretically and experimentally. The chemical structure and composition of thin films of both dipeptides on TiO2 were investigated by XPS (X-ray photoelectron spectroscopy). Theoretical ab-initio calculations (ΔSCF) were also performed to simulate the spectra allowing a direct comparison between experiment and theory.

  15. Suppression of Parallel Transport in Turbulent Magnetized Plasmas and Its Impact on the Non-thermal and Thermal Aspects of Solar Flares

    NASA Astrophysics Data System (ADS)

    Bian, Nicolas H.; Kontar, Eduard P.; Emslie, A. Gordon

    2016-06-01

    The transport of the energy contained in electrons, both thermal and suprathermal, in solar flares plays a key role in our understanding of many aspects of the flare phenomenon, from the spatial distribution of hard X-ray emission to global energetics. Motivated by recent RHESSI observations that point to the existence of a mechanism that confines electrons to the coronal parts of flare loops more effectively than Coulomb collisions, we here consider the impact of pitch-angle scattering off turbulent magnetic fluctuations on the parallel transport of electrons in flaring coronal loops. It is shown that the presence of such a scattering mechanism in addition to Coulomb collisional scattering can significantly reduce the parallel thermal and electrical conductivities relative to their collisional values. We provide illustrative expressions for the resulting thermoelectric coefficients that relate the thermal flux and electrical current density to the temperature gradient and the applied electric field. We then evaluate the effect of these modified transport coefficients on the flare coronal temperature that can be attained, on the post-impulsive-phase cooling of heated coronal plasma, and on the importance of the beam-neutralizing return current on both ambient heating and the energy loss rate of accelerated electrons. We also discuss the possible ways in which anomalous transport processes have an impact on the required overall energy associated with accelerated electrons in solar flares.

  16. PKCε inhibits isolation and stemness of side population cells via the suppression of ABCB1 transporter and PI3K/Akt, MAPK/ERK signaling in renal cell carcinoma cell line 769P.

    PubMed

    Huang, Bin; Fu, Shun Jun; Fan, Wen Zhe; Wang, Zhong Hua; Chen, Ze Bin; Guo, Sheng Jie; Chen, Jun Xing; Qiu, Shao Peng

    2016-06-28

    Protein kinase C epsilon (PKCε), a member of the novel PKC family, is known to be a transforming oncogene and tumor biomarker for many human solid cancers including renal cell carcinoma (RCC). We isolated side population (SP) cells from the RCC 769P cell line, and proved that those cells possess cancer stem cell (CSC) characteristics. In this study, to identify the function of PKCε in cancer stemness of 769P SP cells, we reduced the expression of PKCε in those cells, following the results demonstrated that PKCε depletion had a negative correlation with the existence of SP cells in 769P cell line. Down-regulation of PKCε also suppresses the CSC potential of sorted 769P SP cells in several ways: proliferation potential, resistance to chemotherapeutics and in vivo tumor formation ability. Our study also reveals that PKCε is associated with ABCB1 and this association probably contributed to the SP cells isolation from 769P cell line. Furthermore, the expression of ABCB1 is directly regulated by PKCε. Additionally, after the depletion of PKCε, the phosphorylation of pAkt, pStat3 and pERK was apparently suppressed in 769P SP cells, whereas PKCε overexpression could promote the phosphorylation of AKT, STAT3 and ERK in 769P Non-SP cells. Overall, PKCε down-regulation suppresses sorting and the cancer stem-like phenotype of RCC 769P SP cells through the regulation of ABCB1 transporter and the PI3K/Akt, Stat3 and MAPK/ERK pathways that are dependent on the phosphorylation effects. Thus, PKCε may work as an important mediator in cancer stem cell pathogenesis of renal cell cancer. PMID:27037060

  17. Hysteresis-Suppressed High-Efficiency Flexible Perovskite Solar Cells Using Solid-State Ionic-Liquids for Effective Electron Transport.

    PubMed

    Yang, Dong; Yang, Ruixia; Ren, Xiaodong; Zhu, Xuejie; Yang, Zhou; Li, Can; Liu, Shengzhong Frank

    2016-07-01

    An efficiency of flexible perovskite solar cells (Pvs-SCs) of 16.09% is achieved, the highest value reported for flexible Pvs-SCs to date. The outstanding performance is attributed to the superior features of alternative electron-transport materials, such as antireflection, a suitable work function, high electron mobility, and a reduced trap-state density of the perovskite material. PMID:27147394

  18. Suppression of Parallel Transport in Turbulent Magnetized Plasmas and Its Impact on Non-Thermal and Thermal Aspects of Solar Flares

    NASA Astrophysics Data System (ADS)

    Emslie, A. Gordon; Bian, Nicolas H.; Kontar, Eduard

    2016-05-01

    Motivated by recent RHESSI observations that point to the existence of a mechanism that confines electrons to the coronal parts of flare loops more effectively than Coulomb collisions, we consider the impact of pitch-angle scattering off turbulent magnetic fluctuations on the parallel transport of electrons in flaring coronal loops. It is shown that the presence of such a scattering mechanism in addition to Coulomb collisional scattering can significantly reduce the parallel thermal and electrical conductivities relative to their collisional values. We provide illustrative expressions for the resulting thermoelectric coefficients that relate the thermal flux and electrical current density to the temperature gradient and the applied electric field. We then evaluate the effect of these modified transport coefficients on several items of interest to the modeling of flares, including: the peak flare coronal temperature that can be attained, the post-impulsive-phase cooling time of heated coronal plasma, and the importance of the beam-neutralizing return current on both ambient heating and the energy loss rate of accelerated electrons. We also discuss the ways in which anomalous transport processes have an impact on the required overall energy content of accelerated electrons in solar flares.

  19. Mass spectrometry of oligopeptides in the presence of large amounts of alkali halides using desorption/ionization induced by neutral cluster impact.

    PubMed

    Portz, André; Baur, Markus; Gebhardt, Christoph R; Dürr, Michael

    2016-06-01

    Oligopeptides in the presence of large amounts of salt were desorbed and ionized using desorption/ionization induced by neutral clusters (DINeC) for further analysis by means of mass spectrometry (MS). Using oligopeptides in alkali halide solutions as a model system, DINeC was shown to yield clear and fragmentation free mass spectra of the biomolecules even from environments with a large excess of salt. The results were traced back to a phase separation between salt and biomolecules during sample preparation. The ratio between alkali metal complexes [M+A](+) and bare biomolecules [M+H](+) was controlled using different preparation schemes. DINeC was applied to the products of a tryptic digest of bovine serum albumin in the presence of sodium chloride; the results of a mass fingerprint analysis did not show a major difference for the spectra with and without salt in the original solution. The metal-ion/peptide interaction was further investigated by means of tandem-MS. PMID:26825286

  20. Expression of a putative ATPase suppresses the growth defect of a yeast potassium transport mutant: identification of a mammalian member of the Clp/HSP104 family.

    PubMed

    Périer, F; Radeke, C M; Raab-Graham, K F; Vandenberg, C A

    1995-01-23

    A cDNA encoding a novel mammalian member of the Clp/HSP104 family was isolated from a mouse macrophage-like cell line (J774.1) cDNA library by suppression of the growth defect of a Saccharomyces cerevisiae trk1 trk2 double mutant. The full-length version of this cDNA, termed SKD3, encodes a putative 76-kDa protein of 677 amino acids (aa). The deduced aa sequence of the SKD3 polypeptide contains four ankyrin-like repeats in the N-terminal domain and a single ATP-binding consensus site in the C-terminal domain. The 378-aa C-terminal domain of SKD3 has 57-64% similarity (30-40% identity) with members of the Clp/HSP104 family, including the ClpA regulatory subunit of the Clp protease and S. cerevisiae heat-shock protein 104. Northern analysis showed that the 2.3-kb SKD3 transcript is present in a wide variety of tissues, is abundant in mouse heart, skeletal muscle and kidney, and is most abundant in testis. Members of the Clp/HSP104 family have been identified previously from bacteria, yeast and chloroplasts, and are ATPases regulating Clp protease activity and specificity, or mediating cellular responses involved in thermotolerance. SKD3 is the first member of this protein family identified in a higher eukaryote. PMID:7835694

  1. Determination of Oligopeptide Diversity within a Natural Population of Microcystis spp. (Cyanobacteria) by Typing Single Colonies by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

    PubMed Central

    Fastner, Jutta; Erhard, Marcel; von Döhren, Hans

    2001-01-01

    Besides the most prominent peptide toxin, microcystin, the cyanobacteria Microcystis spp. have been shown to produce a large variety of other bioactive oligopeptides. We investigated for the first time the oligopeptide diversity within a natural Microcystis population by analyzing single colonies directly with matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). The results demonstrate a high diversity of known cyanobacterial peptides such as microcystins, anabaenopeptins, microginins, aeruginosins, and cyanopeptolins, but also many unknown substances in the Microcystis colonies. Oligopeptide patterns were mostly related to specific Microcystis taxa. Microcystis aeruginosa (Kütz.) Kütz. colonies contained mainly microcystins, occasionally accompanied by aeruginosins. In contrast, microcystins were not detected in Microcystis ichthyoblabe Kütz.; instead, colonies of this species contained anabaenopeptins and/or microginins or unknown peptides. Within a third group, Microcystis wesenbergii (Kom.) Kom. in Kondr., chiefly a cyanopeptolin and an unknown peptide were found. Similar patterns, however, were also found in colonies which could not be identified to species level. The significance of oligopeptides as a chemotaxonomic tool within the genus Microcystis is discussed. It could be demonstrated that the typing of single colonies by MALDI-TOF MS may be a valuable tool for ecological studies of the genus Microcystis as well as in early warning of toxic cyanobacterial blooms. PMID:11679328

  2. Paeonol suppresses lipid accumulation in macrophages via upregulation of the ATP‑binding cassette transporter A1 and downregulation of the cluster of differentiation 36.

    PubMed

    Li, Xiuying; Zhou, Yuanda; Yu, Chao; Yang, Hui; Zhang, Chengzhi; Ye, Yun; Xiao, Shunlin

    2015-02-01

    Paeonol, a potent antioxidant isolated from cortex moutan, possesses athero‑protective activity, yet the detailed mechanisms are not fully investigated. This study was conducted to explore the role of paeonol and its underlying mechanisms in RAW264.7 macrophages and apolipoprotein E‑deficient (ApoE(‑/‑)) mice. Paeonol treatment significantly attenuated intracellular lipid accumulation in macrophages, which may be the result of decreased oxidized low‑density lipoprotein (ox‑LDL) uptake and increased cholesterol efflux. Additionally, paeonol markedly inhibited the mRNA and protein expression of the cluster of differentiation 36 (CD36) by decreasing nuclear translocation of c‑Jun [a subunit of activator protein‑1 (AP‑1)]. Moreover, paeonol upregulated the protein stability of ATP‑binding cassette transporter A1 (ABCA1) by inhibiting calpain activity, while ABCA1 mRNA expression was not altered. Furthermore, small hairpin RNA (shRNA) targeting haem oxygenase‑1 (HO‑1) inhibited the paeonol‑mediated beneficial effects on the expression of c‑Jun, CD36, ABCA1, calpain activity and lipid accumulation in macrophages. Accordingly, paeonol retarded the progress of atherosclerosis in ApoE(‑/‑) mice and modulated the expression of CD36 and ABCA1 in aortas similarly to that observed in macrophages. These results indicate that paeonol provides protective effects on foam cell formation by a novel HO‑1‑dependent mediation of cholesterol efflux and lipid accumulation in macrophages. PMID:25405950

  3. Cheese peptidomics: a detailed study on the evolution of the oligopeptide fraction in Parmigiano-Reggiano cheese from curd to 24 months of aging.

    PubMed

    Sforza, S; Cavatorta, V; Lambertini, F; Galaverna, G; Dossena, A; Marchelli, R

    2012-07-01

    In this work, we performed a detailed evaluation of the evolution of the oligopeptide fractions in samples of Parmigiano-Reggiano cheese from the curd up to 24 mo of aging. The samples were taken from wheels produced the same day, in the same factory, from the same milk, during the same caseification process, thus simplifying the natural variability of a whey-based starter fermentation. This unique and homogeneous sampling plan, never reported before in the literature, provided a detailed study of the peptides produced by enzymatic events during Parmigiano-Reggiano aging. Given the large dimensions of the 35-kg wheels of Parmigiano-Reggiano, samples were taken from both the internal and external parts of the cheese, to evidence eventual differences in the oligopeptide composition of the different parts. Fifty-seven peptides were considered, being among the most abundant during at least one of the periods of ripening considered, and their semiquantification indicated that the peptide fraction of Parmigiano-Reggiano cheese constantly evolves during the aging period. Five trends in its evolution were outlined, which could be clearly correlated to the enzymatic activities present in the cheese, making it possible to discriminate cheeses according to their aging time. Several known bioactive peptides were also found to be present in Parmigiano-Reggiano cheese samples, and for the first time, the age at which they are most abundant has been identified. Aged cheeses have been shown to be dominated by nonproteolytic aminoacyl derivatives, a new class of peptide-like molecules recently reported. Finally, the changing peptide pattern may be related to the changing enzymatic activities occurring inside the cheeses during the aging period, which, in turn, are also related to the microbiological composition. PMID:22720910

  4. Astragaloside IV facilitates glucose transport in C2C12 myotubes through the IRS1/AKT pathway and suppresses the palmitate-induced activation of the IKK/IκBα pathway.

    PubMed

    Zhu, Rongfeng; Zheng, Jianjun; Chen, Lizhen; Gu, Bin; Huang, Shengli

    2016-06-01

    Astragaloside IV is a monomer isolated from Astragalus membranaceus (Fisch.) Bunge, which is one of the most widely used plant-derived drugs in traditional Chinese medicine for diabetes therapy. In the present study, we aimed to examine the effects of astragaloside IV on glucose in C2C12 myotubes and the underlying molecular mechanisms responsible for these effects. Four-day differentiated C2C12 myotubes were exposed to palmitate for 16 h in order to establish a model of insulin resistance and 3H glucose uptake, using 2-Deoxy‑D‑[1,2-3H(N)]-glucose (radiolabeled 2-DG), was detected. Astragaloside IV was added 2 h prior to palmitate exposure. The translocation of glucose transporter 4 (GLUT4) was evaluated by subcellular fractionation, and the expression of insulin signaling molecules such as insulin receptor β (IRβ), insulin receptor substrate (IRS)1/protein kinase B (AKT) and inhibitory κB kinase (IKK)/inhibitor-κBα (IκBα), which are associated with insulin signal transduction, were assessed in the basal or the insulin‑stimulated state using western blot analysis or RT-PCR. We also examined the mRNA expression of monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), tumor necrosis factor α (TNFα) and Toll‑like receptor 4 (TLR4). Taken together, these findings demonstrated that astragaloside IV facilitates glucose transport in C2C12 myotubes through a mechanism involving the IRS1/AKT pathway, and suppresses the palmitate-induced activation of the IKK/IκBα pathway. PMID:27082050

  5. Growth hormone suppression test

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  6. Dexamethasone suppression test

    MedlinePlus

    Dexamethasone suppression test measures whether adrenocorticotrophic hormone ( ACTH ) secretion by the pituitary can be suppressed. ... During this test, you will receive dexamethasone. This is a strong ... your blood is drawn so that the cortisol level in your blood ...

  7. Dexamethasone suppression test

    MedlinePlus

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medication. Afterward, your blood is drawn ...

  8. Growth hormone suppression test

    MedlinePlus

    The growth hormone suppression test determines whether growth hormone production is being suppressed by high blood sugar. ... away. The lab measures the glucose and growth hormone (GH) levels in each sample.

  9. Fire Suppression and Response

    NASA Technical Reports Server (NTRS)

    Ruff, Gary A.

    2004-01-01

    This report is concerned with the following topics regarding fire suppression:What is the relative effectiveness of candidate suppressants to extinguish a representative fire in reduced gravity, including high-O2 mole fraction, low -pressure environments? What are the relative advantages and disadvantages of physically acting and chemically-acting agents in spacecraft fire suppression? What are the O2 mole fraction and absolute pressure below which a fire cannot exist? What effect does gas-phase radiation play in the overall fire and post-fire environments? Are the candidate suppressants effective to extinguish fires on practical solid fuels? What is required to suppress non-flaming fires (smoldering and deep seated fires) in reduced gravity? How can idealized space experiment results be applied to a practical fire scenario? What is the optimal agent deployment strategy for space fire suppression?

  10. Peptide bonds affect the formation of haloacetamides, an emerging class of N-DBPs in drinking water: free amino acids versus oligopeptides.

    PubMed

    Chu, Wenhai; Li, Xin; Gao, Naiyun; Deng, Yang; Yin, Daqiang; Li, Dongmei; Chu, Tengfei

    2015-01-01

    Haloacetamides (HAcAms), an emerging class of nitrogenous disinfection by-products (N-DBPs) of health concern, have been frequently identified in drinking waters. It has long been appreciated that free amino acids (AAs), accounting for a small fraction of the dissolved organic nitrogen (DON) pool, can form dichloroacetamide (DCAcAm) during chlorination. However, the information regarding the impacts of combined AAs, which contribute to the greatest identifiable DON portion in natural waters, is limited. In this study, we compared the formation of HAcAms from free AAs (tyrosine [Tyr] and alanine [Ala]) and combined AAs (Tyr-Ala, Ala-Tyr, Tyr-Tyr-Tyr, Ala-Ala-Ala), and found that HAcAm formation from the chlorination of AAs in combined forms (oligopeptides) significantly exhibited a different pattern with HAcAm formation from free AAs. Due to the presence of peptide bonds in tripeptides, Tyr-Tyr-Tyr and Ala-Ala-Ala produced trichloroacetamide (TCAcAm) in which free AAs was unable to form TCAcAm during chlorination. Moreover, peptide bond in tripeptides formed more tri-HAcAms than di-HAcAms in the presence of bromide. Therefore, the peptide bond may be an important indicator to predict the formation of specific N-DBPs in chlorination. The increased use of algal- and wastewater-impacted water as drinking water sources will increase health concerns over exposure to HAcAms in drinking water. PMID:26394759

  11. Peptide bonds affect the formation of haloacetamides, an emerging class of N-DBPs in drinking water: free amino acids versus oligopeptides

    PubMed Central

    Chu, Wenhai; Li, Xin; Gao, Naiyun; Deng, Yang; Yin, Daqiang; Li, Dongmei; Chu, Tengfei

    2015-01-01

    Haloacetamides (HAcAms), an emerging class of nitrogenous disinfection by-products (N-DBPs) of health concern, have been frequently identified in drinking waters. It has long been appreciated that free amino acids (AAs), accounting for a small fraction of the dissolved organic nitrogen (DON) pool, can form dichloroacetamide (DCAcAm) during chlorination. However, the information regarding the impacts of combined AAs, which contribute to the greatest identifiable DON portion in natural waters, is limited. In this study, we compared the formation of HAcAms from free AAs (tyrosine [Tyr] and alanine [Ala]) and combined AAs (Tyr-Ala, Ala-Tyr, Tyr-Tyr-Tyr, Ala-Ala-Ala), and found that HAcAm formation from the chlorination of AAs in combined forms (oligopeptides) significantly exhibited a different pattern with HAcAm formation from free AAs. Due to the presence of peptide bonds in tripeptides, Tyr-Tyr-Tyr and Ala-Ala-Ala produced trichloroacetamide (TCAcAm) in which free AAs was unable to form TCAcAm during chlorination. Moreover, peptide bond in tripeptides formed more tri-HAcAms than di-HAcAms in the presence of bromide. Therefore, the peptide bond may be an important indicator to predict the formation of specific N-DBPs in chlorination. The increased use of algal- and wastewater-impacted water as drinking water sources will increase health concerns over exposure to HAcAms in drinking water. PMID:26394759

  12. Preparation and functional evaluation of oligopeptide-enriched hydrolysate from shrimp (Acetes chinensis) treated with crude protease from Bacillus sp. SM98011.

    PubMed

    He, Hailun; Chen, Xiulan; Sun, Caiyun; Zhang, Yuzhong; Gao, Peiji

    2006-02-01

    Marine organisms are potentially an untapped source of drugs and value-added food production. Currently, Acetes chinensis is an underutilized shrimp species with low commercial value from the Bo Hai Gulf of China. In this paper, the shrimp was digested by a crude protease from Bacillus sp. SM98011 and filtered through a 3 kDa ultrafiltration membrane. Biological functions of the hydrolysate and ultrafiltrate were then assayed. The analyses showed that 41% of the oligopeptides in the ultrafiltrate had a molecular mass lower than 3 kDa. The antioxidant activities of the hydrolysate and ultrafiltrate were determined through the scavenger activity of the hydroxyl radical, with inhibitions of 42.38% and 67.95%, respectively. The hydrolysate and ultrafiltrate also had good Angiotensin-I-converting enzyme (ACE) inhibitory activity, with IC50 values of 0.98 mg/ml and 0.22 mg/ml, respectively. In addition, Chitin and chitosan were recovered from the hydrolytic sediment using a much smaller volume of strong acids and bases than is normally needed. With this method, we have shown that A. chinensis can be utilized to generate a high value-added product, and have revealed its hidden potential in the production of functional foods and ACE inhibitory peptides. PMID:15935656

  13. Molecular recognition between oligopeptides and nucleic acids: DNA binding specificity of a series of bis netropsin analogues deduced from footprinting analysis.

    PubMed

    Kissinger, K L; Dabrowiak, J C; Lown, J W

    1990-01-01

    A series of tether-linked bis netropsins have been synthesized in order to assess the phasing problem, which arises because of the lack of dimensional correspondence between oligopeptides and oligonucleotides in DNA binding characteristics. The consequences of incorporating variable-length flexible and rigid tethers [poly(methylene), Z and E ethylene, m- and p-phenylene] between the two netropsin-like moieties on the DNA binding properties were assessed by DNase I footprinting. The conformational freedom associated with two netropsins linked by a flexible methylene tether allows ligand binding in both a mono- and bidentate fashion, with bidentate binding requiring a minimum linker length of (CH2)3. For compounds possessing rigid tethers, for example, cis and trans ethylene moieties, the cis geometry excludes bidentate ligation while the trans structure favors it. Bis netropsins possessing aryl linking groups have reduced DNA binding affinities. This is most plausibly due to the aryl groups, which are not coplanar with the netropsin moieties, thus blocking the ligand from penetrating deeply into the minor groove of DNA. PMID:1966670

  14. An Arabidopsis peptide transporter is a member of a new class of membrane transport proteins.

    PubMed Central

    Steiner, H Y; Song, W; Zhang, L; Naider, F; Becker, J M; Stacey, G

    1994-01-01

    An Arabidopsis peptide transport gene was cloned from an Arabidopsis cDNA library by functionally complementing a yeast peptide transport mutant. The Arabidopsis plant peptide transporter (AtPTR2) allowed growth of yeast cells on dipeptides and tripeptides but not peptides four residues and higher. The plant peptide transporter also conferred sensitivity to a number of ethionine-containing, toxic peptides of chain length three or less and restored the ability to take up radiolabeled dileucine at levels similar to that of the wild type. Dileucine uptake was reduced by the addition of a variety of growth-promoting peptides. The sequence of a cDNA insert of 2.8 kb indicated an open reading frame encoding a 610-amino acid polypeptide (67.5 kD). Hydropathy analysis predicted a highly hydrophobic protein with a number of potential transmembrane segments. At the amino acid level, the Arabidopsis plant peptide transporter shows 24.6, 28.5, and 45.2% identity to the Arabidopsis nitrate-inducible nitrate transporter (CHL1), the rabbit small intestine oligopeptide transporter (PepT1), and the yeast peptide transporter (Ptr2p), respectively, but little identity to other proteins known to be involved in peptide transport. Root growth of Arabidopsis seedlings exposed to ethionine-containing toxic peptides was inhibited, and growth was restored by the addition of certain peptides shown to compete with dileucine uptake in yeast expressing the Arabidopsis transport gene. Consistent with the observed inhibition of root growth by toxic peptides, the peptide transporter is expressed in the roots of Arabidopsis seedlings. This study represents the characterization of a plant peptide transporter that is a member of a new class of related membrane transport proteins. PMID:7919993

  15. Different modes of dipeptidyl peptidase IV (CD26) inhibition by oligopeptides derived from the N-terminus of HIV-1 Tat indicate at least two inhibitor binding sites.

    PubMed

    Lorey, Susan; Stöckel-Maschek, Angela; Faust, Jürgen; Brandt, Wolfgang; Stiebitz, Beate; Gorrell, Mark D; Kähne, Thilo; Mrestani-Klaus, Carmen; Wrenger, Sabine; Reinhold, Dirk; Ansorge, Siegfried; Neubert, Klaus

    2003-05-01

    Dipeptidyl peptidase IV (DP IV, CD26) plays an essential role in the activation and proliferation of lymphocytes, which is shown by the immunosuppressive effects of synthetic DP IV inhibitors. Similarly, both human immunodeficiency virus-1 (HIV-1) Tat protein and the N-terminal peptide Tat(1-9) inhibit DP IV activity and T cell proliferation. Therefore, the N-terminal amino acid sequence of HIV-1 Tat is important for the inhibition of DP IV. Recently, we characterized the thromboxane A2 receptor peptide TXA2-R(1-9), bearing the N-terminal MWP sequence motif, as a potent DP IV inhibitor possibly playing a functional role during antigen presentation by inhibiting T cell-expressed DP IV [Wrenger, S., Faust, J., Mrestani-Klaus, C., Fengler, A., Stöckel-Maschek, A., Lorey, S., Kähne, T., Brandt, W., Neubert, K., Ansorge, S. & Reinhold, D. (2000) J. Biol. Chem.275, 22180-22186]. Here, we demonstrate that amino acid substitutions at different positions of Tat(1-9) can result in a change of the inhibition type. Certain Tat(1-9)-related peptides are found to be competitive, and others linear mixed-type or parabolic mixed-type inhibitors indicating different inhibitor binding sites on DP IV, at the active site and out of the active site. The parabolic mixed-type mechanism, attributed to both non-mutually exclusive inhibitor binding sites of the enzyme, is described in detail. From the kinetic investigations and molecular modeling experiments, possible interactions of the oligopeptides with specified amino acids of DP IV are suggested. These findings give new insights for the development of more potent and specific peptide-based DP IV inhibitors. Such inhibitors could be useful for the treatment of autoimmune and inflammatory diseases. PMID:12752434

  16. BOP: a basic phenylalanine-rich oligo-peptide located on the surface of glycolate oxidase influences its pI values.

    PubMed

    Xu, Jun; Du, Yingqing; Ma, Guangzhi; Xu, Jie

    2010-06-01

    Glycolate oxidase (GO) consists of identical subunits and therefore should show one definite pI value, but the isolated GO exhibited a range of pIs. This study investigated the underlying cause of this phenomenon. GO was purified and showed a molecular weight of 40 kDa by SDS-PAGE. Elution behavior on DEAE-cellulose chromatography and cellulose acetate membrane electrophoresis indicated that the purified GO was highly basic (pI>10.0). Repeated IEF and cIEF analysis showed that the pI of the purified GO was in the range of 10.0-3.25, either in a smear form or as distinct bands. 2-DE analysis showed that the 40 kDa subunit of GO displayed variable pIs from 9.6 to 3.65. It was likely that the purified GO was actually a complex consisted of GO and an unknown protein. CE-SDS, SDS-cellulose acetate membrane electrophoresis and amino acid compositions indicated that the unknown protein was a highly basic polymer (BP) consisting of basic and phenylalanine-rich oligo-peptide (BOP). Many BOPs are located on the surface of the acidic GO via ionic and hydrophobic interactions and formed GO-BOP complex (GC), resulting in a highly basic GC although GO itself was acidic. This hypothesis was further supported by the facts that anti-GC serum failed to recognize GO, and GC showed a peak at 257 nm although GO has few phenylalanine residues. Irregular and incomplete disassociation between GO and BOP was observed in IEF and cIEF, resulting in various intermediates with different ratios of GO/BOP, which could be the reason for the range of pIs observed for GO. PMID:20496344

  17. Cough suppression disorders spectrum.

    PubMed

    Reich, Jerome M

    2014-02-01

    Volitional cough suppression, identified exclusively in females, is an unusual causal mechanism for instances of lobar atalectasis and bronchiectasis. It is a postulated mechanism for the genesis of Lady Windermere Syndrome. PMID:24462261

  18. A novel nuclear DnaJ protein, DNAJC8, can suppress the formation of spinocerebellar ataxia 3 polyglutamine aggregation in a J-domain independent manner.

    PubMed

    Ito, Norie; Kamiguchi, Kenjiro; Nakanishi, Katsuya; Sokolovskya, Alice; Hirohashi, Yoshihiko; Tamura, Yasuaki; Murai, Aiko; Yamamoto, Eri; Kanaseki, Takayuki; Tsukahara, Tomohide; Kochin, Vitaly; Chiba, Susumu; Shimohama, Shun; Sato, Noriyuki; Torigoe, Toshihiko

    2016-06-10

    Polyglutamine (polyQ) diseases comprise neurodegenerative disorders caused by expression of expanded polyQ-containing proteins. The cytotoxicity of the expanded polyQ-containing proteins is closely associated with aggregate formation. In this study, we report that a novel J-protein, DNAJ (HSP40) Homolog, Subfamily C, Member 8 (DNAJC8), suppresses the aggregation of polyQ-containing protein in a cellular model of spinocerebellar ataxia type 3 (SCA3), which is also known as Machado-Joseph disease. Overexpression of DNAJC8 in SH-SY5Y neuroblastoma cells significantly reduced the polyQ aggregation and apoptosis, and DNAJC8 was co-localized with the polyQ aggregation in the cell nucleus. Deletion mutants of DNAJC8 revealed that the C-terminal domain of DNAJC8 was essential for the suppression of polyQ aggregation, whereas the J-domain was dispensable. Furthermore, 22-mer oligopeptide derived from C-termilal domain could suppress the polyQ aggregation. These results indicate that DNAJC8 can suppress the polyQ aggregation via a distinct mechanism independent of HSP70-based chaperone machinery and have a unique protective role against the aggregation of expanded polyQ-containing proteins such as pathogenic ataxin-3 proteins. PMID:27133716

  19. STE6, the yeast a-factor transporter.

    PubMed

    Michaelis, S

    1993-02-01

    In eukaryotic cells, most extracellular proteins exit the cell via the classical secretory pathway (ER-->Golgi-->secretory vesicles). A notable exception to this pattern is the Saccharomyces cerevisiae mating pheromone alpha-factor, an isoprenylated, methylated, oligopeptide signaling molecule which uses a distinctly non-classical mechanism for secretion. Export of alpha-factor from the yeast cell is mediated by STE6, a member of the ABC protein superfamily. STE6 is one of the few eukaryotic ABC proteins for which a true physiological substrate is known. The ability to carry out molecular manipulations with ease in yeast, together with the possibility of probing substrate-transporter interactions via genetic analysis, affords an excellent opportunity to rigorously dissect the workings of this ABC family member. PMID:8095825

  20. Improved gene expression in resting macrophages using an oligopeptide derived from Vpr of human immunodeficiency virus type-1

    SciTech Connect

    Mizoguchi, Izuru; Ooe, Yoshihiro; Hoshino, Shigeki; Shimura, Mari; Kasahara, Tadashi; Kano, Shigeyuki; Ohta, Toshiko; Takaku, Fumimaro; Nakayama, Yasuhide; Ishizaka, Yukihito . E-mail: zakay@ri.imcj.go.jp

    2005-12-23

    Vpr, an accessory gene product of human immunodeficiency virus type-1, is thought to transport a viral DNA from the cytoplasm to the nucleus in resting macrophages. Previously, we reported that a peptide encompassing amino acids 52-78 of Vpr (C45D18) promotes the nuclear trafficking of recombinant proteins that are conjugated with C45D18. Here, we present evidence that C45D18, when conjugated with a six-branched cationic polymer of poly(N,N-dimethylaminopropylacrylamide)-block-oligo(4-aminostyrene) (SV: star vector), facilitates gene expression in resting macrophages. Although there was no difference between SV alone and C45D18-SV with respect to gene transduction into growing cells, C45D18-SV resulted in more than 40-fold greater expression of the exogenous gene upon transduction into chemically differentiated macrophages and human quiescent monocyte-derived macrophages. The data suggest that C45D18 contributes to improving the ability of a non-viral vector to transduce macrophages with exogenous genes and we discuss its further application.

  1. A redox-sensitive, oligopeptide-guided, self-assembling, and efficiency-enhanced (ROSE) system for functional delivery of microRNA therapeutics for treatment of hepatocellular carcinoma.

    PubMed

    Hu, Qida; Wang, Kai; Sun, Xu; Li, Yang; Fu, Qihan; Liang, Tingbo; Tang, Guping

    2016-10-01

    Lack of efficient adjuvant therapy contributes to a high incidence of recurrence and metastasis of hepatocellular carcinoma (HCC). A novel therapeutic is required for adjuvant treatment of HCC. We developed a polymer-based nanosystem (ROSE) for functional gene therapy by synthesizing a supramolecular complex self-assembled from polycations and functional adamantyl modules. The ROSE system condensing tumor suppressor microRNA-34a (miR-34a) therapeutics becomes ROSE/miR-34a nanoparticles that could facilitate gene transfection in HCC cells with satisfied stability and efficiency, possibly due to proton sponge effect by polycations, PEGlyation protection, and controlled release by breakdown of disulfide bonds. Meanwhile, modification with a targeting oligopeptide SP94 in ROSE/miR-34a enables approximately higher affinity for LM3 HCC cells than hepatocytes in vitro and greater HCC specificity in vivo. Furthermore, ROSE/miR-34a nanoparticles significantly inhibits HCC cell proliferation and in vivo tumor growth, representing a notable effect improvement over conventional gene delivery strategies. ROSE/miR-34a, featuring redox-responsiveness, oligopeptide-guided specificity, self-assembly, and enhanced transfection, is therefore a potential therapeutic agent in future adjuvant therapy for HCC treatment. PMID:27459325

  2. Thermopower signatures and spectroscopy of the canyon of conductance suppression

    NASA Astrophysics Data System (ADS)

    Kiršanskas, G.; Hammarberg, S.; Karlström, O.; Wacker, A.

    2016-07-01

    Interference effects in quantum dots between different transport channels can lead to a strong suppression of conductance, which cuts like a canyon through the common conductance plot [Phys. Rev. Lett. 104, 186804 (2010), 10.1103/PhysRevLett.104.186804]. In the present work we consider the thermoelectric transport properties of the canyon of conductance suppression using the second-order von Neumann approach. We observe a characteristic signal for the zeros of the thermopower. This demonstrates that thermoelectric measurements are an interesting complimentary tool to study complex phenomena for transport through confined systems.

  3. Explosion suppression system

    DOEpatents

    Sapko, Michael J.; Cortese, Robert A.

    1992-01-01

    An explosion suppression system and triggering apparatus therefor are provided for quenching gas and dust explosions. An electrically actuated suppression mechanism which dispenses an extinguishing agent into the path ahead of the propagating flame is actuated by a triggering device which is light powered. This triggering device is located upstream of the propagating flame and converts light from the flame to an electrical actuation signal. A pressure arming device electrically connects the triggering device to the suppression device only when the explosion is sensed by a further characteristic thereof beside the flame such as the pioneer pressure wave. The light powered triggering device includes a solar panel which is disposed in the path of the explosion and oriented between horizontally downward and vertical. Testing mechanisms are also preferably provided to test the operation of the solar panel and detonator as well as the pressure arming mechanism.

  4. Predictions of Cleavability of Calpain Proteolysis by Quantitative Structure-Activity Relationship Analysis Using Newly Determined Cleavage Sites and Catalytic Efficiencies of an Oligopeptide Array*

    PubMed Central

    Shinkai-Ouchi, Fumiko; Koyama, Suguru; Ono, Yasuko; Hata, Shoji; Ojima, Koichi; Shindo, Mayumi; duVerle, David; Ueno, Mika; Kitamura, Fujiko; Doi, Naoko; Takigawa, Ichigaku; Mamitsuka, Hiroshi; Sorimachi, Hiroyuki

    2016-01-01

    Calpains are intracellular Ca2+-regulated cysteine proteases that are essential for various cellular functions. Mammalian conventional calpains (calpain-1 and calpain-2) modulate the structure and function of their substrates by limited proteolysis. Thus, it is critically important to determine the site(s) in proteins at which calpains cleave. However, the calpains' substrate specificity remains unclear, because the amino acid (aa) sequences around their cleavage sites are very diverse. To clarify calpains' substrate specificities, 84 20-mer oligopeptides, corresponding to P10-P10′ of reported cleavage site sequences, were proteolyzed by calpains, and the catalytic efficiencies (kcat/Km) were globally determined by LC/MS. This analysis revealed 483 cleavage site sequences, including 360 novel ones. The kcat/Kms for 119 sites ranged from 12.5–1,710 M−1s−1. Although most sites were cleaved by both calpain-1 and −2 with a similar kcat/Km, sequence comparisons revealed distinct aa preferences at P9-P7/P2/P5′. The aa compositions of the novel sites were not statistically different from those of previously reported sites as a whole, suggesting calpains have a strict implicit rule for sequence specificity, and that the limited proteolysis of intact substrates is because of substrates' higher-order structures. Cleavage position frequencies indicated that longer sequences N-terminal to the cleavage site (P-sites) were preferred for proteolysis over C-terminal (P′-sites). Quantitative structure-activity relationship (QSAR) analyses using partial least-squares regression and >1,300 aa descriptors achieved kcat/Km prediction with r = 0.834, and binary-QSAR modeling attained an 87.5% positive prediction value for 132 reported calpain cleavage sites independent of our model construction. These results outperformed previous calpain cleavage predictors, and revealed the importance of the P2, P3′, and P4′ sites, and P1-P2 cooperativity. Furthermore, using our

  5. Predictions of Cleavability of Calpain Proteolysis by Quantitative Structure-Activity Relationship Analysis Using Newly Determined Cleavage Sites and Catalytic Efficiencies of an Oligopeptide Array.

    PubMed

    Shinkai-Ouchi, Fumiko; Koyama, Suguru; Ono, Yasuko; Hata, Shoji; Ojima, Koichi; Shindo, Mayumi; duVerle, David; Ueno, Mika; Kitamura, Fujiko; Doi, Naoko; Takigawa, Ichigaku; Mamitsuka, Hiroshi; Sorimachi, Hiroyuki

    2016-04-01

    Calpains are intracellular Ca(2+)-regulated cysteine proteases that are essential for various cellular functions. Mammalian conventional calpains (calpain-1 and calpain-2) modulate the structure and function of their substrates by limited proteolysis. Thus, it is critically important to determine the site(s) in proteins at which calpains cleave. However, the calpains' substrate specificity remains unclear, because the amino acid (aa) sequences around their cleavage sites are very diverse. To clarify calpains' substrate specificities, 84 20-mer oligopeptides, corresponding to P10-P10' of reported cleavage site sequences, were proteolyzed by calpains, and the catalytic efficiencies (kcat/Km) were globally determined by LC/MS. This analysis revealed 483 cleavage site sequences, including 360 novel ones. Thekcat/Kms for 119 sites ranged from 12.5-1,710 M(-1)s(-1) Although most sites were cleaved by both calpain-1 and -2 with a similarkcat/Km, sequence comparisons revealed distinct aa preferences at P9-P7/P2/P5'. The aa compositions of the novel sites were not statistically different from those of previously reported sites as a whole, suggesting calpains have a strict implicit rule for sequence specificity, and that the limited proteolysis of intact substrates is because of substrates' higher-order structures. Cleavage position frequencies indicated that longer sequences N-terminal to the cleavage site (P-sites) were preferred for proteolysis over C-terminal (P'-sites). Quantitative structure-activity relationship (QSAR) analyses using partial least-squares regression and >1,300 aa descriptors achievedkcat/Kmprediction withr= 0.834, and binary-QSAR modeling attained an 87.5% positive prediction value for 132 reported calpain cleavage sites independent of our model construction. These results outperformed previous calpain cleavage predictors, and revealed the importance of the P2, P3', and P4' sites, and P1-P2 cooperativity. Furthermore, using our binary-QSAR model

  6. Monoclonal anti-acid-labile subunit oligopeptide antibodies and their use in a two-site immunoassay for ALS measurement in humans.

    PubMed

    Stadler, S; Wu, Z; Dressendörfer, R A; Morrison, K M; Khare, A; Lee, P D; Strasburger, C J

    2001-06-01

    Quantification of the acid-labile subunit (ALS) has to date been restricted to immunoassays utilizing polyclonal antibodies. By immunization with N-terminal and C-terminal specific ALS oligopeptides, we generated monoclonal antibodies (mAbs) that target ALS-specific sequences outside the nonspecific leucine-rich repeats in the ALS molecule. For mAb selection, a special screening method was developed. Monoclonal antibody 5C9, which targets the N-terminus of ALS, is immobilized and the anti-ALS mAb 7H3, directed against the C-terminus, is biotinylated and used as tracer Ab. Due to the extreme pH-lability of ALS, changes in immunorecognition of ALS were investigated after acidification for protein unfolding in different pH ranges and in a time-dependent manner. It was determined that acidification of the serum samples to pH 2.7 for 30 min, followed by neutralization and dilution to 1:100 was the optimal acid-neutralization method. For standardization purposes, a serum pool derived from healthy volunteers was assigned the value 1 U/ml ALS. The sandwich assay has a working range with a linear dose-response curve in a log/log system between 0.005 and 10 U/ml. ALS levels in seven acromegalic patients ranged from 2.0 to 4.2 U/ml, and in 12 untreated growth hormone deficient patients from 0.036 to 0.986 U/ml (mean=0.45 U/ml). After 12 months of growth hormone therapy, ALS levels increased significantly to 1.18+/-0.45 U/ml (mean+/-SD; p<0.0006). The increase ranged from 0.48 to 1.4 U/ml. The change in ALS with growth hormone (GH) therapy correlated closer with the change in IGF-I (r=0.798, p=0.0057; Spearman rank correlation) than with the change in insulin-like growth factor binding protein (IGFBP3; r=0.549, p=0.057). This specific sandwich assay for the measurement of ALS provides a potentially valuable indicator of growth hormone secretory status. With this mAb-based immunofluorometric assay, the nonspecific detection of other proteins containing leucine-rich repeat

  7. Photoimmune suppression and photocarcinogenesis.

    PubMed

    Ullrich, Stephen E

    2002-03-01

    The primary cause of non-melanoma skin cancer, the most prevalent form of human neoplasia, is the ultraviolet (UV) radiation found in sunlight. Exposing mice to UV radiation induces skin cancers that are highly antigenic. Upon transfer of an UV-induced skin cancer to a normal syngeneic mouse, the tumor cells are recognized and rapidly destroyed by the immune system of the recipient. This raises the question of how these cancers avoided immune destruction during their development in the UV-irradiated host. This question was answered when it was discovered that in addition to being carcinogenic, UV radiation was also immunosuppressive. Studies with immune suppressed transplantation recipients, and biopsy proven skin cancer patients have confirmed that UV-induced immune suppression is a risk factor for skin cancer development in humans. It is of great importance, therefore, to understand the mechanisms underlying UV-induced immune suppression. The focus of this manuscript will be to use some examples from the more recent scientific literature to review the mechanisms by which UV radiation suppresses the immune response and allows for the progressive outgrowth of antigenic skin tumors. PMID:11861222

  8. Parasitic suppressing circuit

    NASA Technical Reports Server (NTRS)

    Fowler, J. T.; Raposa, F. L. (Inventor)

    1973-01-01

    A circuit for suppressing parasitic oscillations across an inductor operating in a resonant mode is described. The circuit includes a switch means and resistive means connected serially across the inductor. A unidirectional resistive-capacitive network is also connected across the inductor and to the switch means to automatically render the switch means conducting when inductive current through the inductor ceases to flow.

  9. A spray-suppression model for turbulent combustion

    SciTech Connect

    DESJARDIN,PAUL E.; TIESZEN,SHELDON R.; GRITZO,LOUIS A.

    2000-02-14

    A spray-suppression model that captures the effects of liquid suppressant on a turbulent combusting flow is developed and applied to a turbulent diffusion flame with water spray suppression. The spray submodel is based on a stochastic separated flow approach that accounts for the transport and evaporation of liquid droplets. Flame extinguishment is accounted for by using a perfectly stirred reactor (PSR) submodel of turbulent combustion. PSR pre-calculations of flame extinction times are determined using CHEMKIN and are compared to local turbulent time scales of the flow to determine if local flame extinguishment has occurred. The PSR flame extinguishment and spray submodels are incorporated into Sandia's flow fire simulation code, VULCAN, and cases are run for the water spray suppression studies of McCaffrey for turbulent hydrogen-air jet diffusion flames. Predictions of flame temperature decrease and suppression efficiency are compared to experimental data as a function of water mass loading using three assumed values of drop sizes. The results show that the suppression efficiency is highly dependent on the initial droplet size for a given mass loading. A predicted optimal suppression efficiency was observed for the smallest class of droplets while the larger drops show increasing suppression efficiency with increasing mass loading for the range of mass loadings considered. Qualitative agreement to the experiment of suppression efficiency is encouraging, however quantitative agreement is limited due to the uncertainties in the boundary conditions of the experimental data for the water spray.

  10. High polar organic-inorganic hybrid coating stir bar sorptive extraction combined with high performance liquid chromatography-inductively coupled plasma mass spectrometry for the speciation of seleno-amino acids and seleno-oligopeptides in biological samples.

    PubMed

    Mao, Xiangju; Hu, Bin; He, Man; Chen, Beibei

    2012-09-21

    In this work, partially sulfonated polystyrene-titania (PSP-TiO(2)) organic-inorganic hybrid stir bar coating was prepared by sol-gel and blending methods, and a new method of PSP-TiO(2) coating stir bar sorptive extraction (SBSE)-high performance liquid chromatography (HPLC)-inductively coupled plasma mass spectrometry (ICP-MS) was established for the analysis of seleno-amino acids (selenocystine (SeCys(2)), methylseleno-cysteine (MeSeCys), selenomethionine (SeMet) and selenoethionine (SeEt)) and seleno-oligopeptides (γ-glutamyl-Se-methyl-selenocysteine (γ-GluMeSeCys) and selenodiglutathione (GS-Se-SG)) in biological samples. The prepared high polar PSP-TiO(2) hybrid coating avoided the swelling of PSP and cracking of TiO(2) coating by combining the good film-forming property of PSP with the high mechanical strength of TiO(2). The scanning electron microscope (SEM) showed that no obvious swelling and damage occurred for the PSP-TiO(2) hybrid stir bar coating after 30 extraction/desorption cycles. The preparation reproducibility of PSP-TiO(2) coated stir bar, evaluated with the relative standard deviations (RSDs), was in the range of 6.7-12.6% (n=5) in one batch, and 9.9-17.6% (n=7) among different batches. The limits of detection (LODs) of the developed method for six target selenium species were in the range of 50.2-185.5 ngL(-1) (as (77)Se) and 45.9-158.8 ngL(-1) (as (82)Se) with the RSDs within 4.9-11.7%. The dynamic linear range was found to cover three orders of magnitude with correlation coefficient of 0.9995-0.9999. The developed method was applied for the analysis of Certified Reference Material SELM-1 selenium enriched yeast and the determined values were in good agreement with the certified values. The method has also been applied for the analysis of seleno-amino acids and seleno-oligopeptides in human urine and garlic samples. Different from the conventional organic polymer SBSE coatings (such as polydimethylsiloxane, PDMS), the extraction mechanism

  11. Pressure suppression containment system

    DOEpatents

    Gluntz, Douglas M.; Townsend, Harold E.

    1994-03-15

    A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto.

  12. Pressure suppression containment system

    DOEpatents

    Gluntz, D.M.; Townsend, H.E.

    1994-03-15

    A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of-coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto. 6 figures.

  13. Vibrotactile suppression of tinnitus

    NASA Astrophysics Data System (ADS)

    Lenhardt, Martin L.

    2002-05-01

    At the Society's 142nd meeting, the efficacy of high frequency bone conducted stimulation in suppressing tinnitus was presented. The hypothesized mechanism was the reprogramming of frequency tuning of auditory neurons in the central nervous system, secondarily to peripheral hearing loss. This mechanism is unlikely in cases of tinnitus in the presence of normal audiometric sensitivity. There is the possibility that hearing loss above 10 kHz can play a role in tinnitus, an association not thoroughly explored. Somatomotor stimulation influencing the quality of tinnitus has been reported, as have interconnections of the auditory and somatosensory systems. There would appear to be an evolutionary advantage of linking the sensorimotor organization of the external ear and the auditory function of the brainstem in sound localization. Thus, stimulation of the pinna and post auricular area may be a means of suppressing tinnitus. To that end a thin aluminum ceramic bimorph was constructed to fit on the inner surface of the pinna. When driven by low (<100 Hz) and high (>10 kHz) frequencies multiplied by MHz carriers, demodulation in the skin resulted in vibrotactile stimulation. Tactile stimulation was an adjunct to the high frequencies resulting in a multimodal suppressive effect in a small pilot study.

  14. Menstrual suppression: current perspectives

    PubMed Central

    Hillard, Paula Adams

    2014-01-01

    Menstrual suppression to provide relief of menstrual-related symptoms or to manage medical conditions associated with menstrual morbidity or menstrual exacerbation has been used clinically since the development of steroid hormonal therapies. Options range from the extended or continuous use of combined hormonal oral contraceptives, to the use of combined hormonal patches and rings, progestins given in a variety of formulations from intramuscular injection to oral therapies to intrauterine devices, and other agents such as gonadotropin-releasing hormone (GnRH) antagonists. The agents used for menstrual suppression have variable rates of success in inducing amenorrhea, but typically have increasing rates of amenorrhea over time. Therapy may be limited by side effects, most commonly irregular, unscheduled bleeding. These therapies can benefit women’s quality of life, and by stabilizing the hormonal milieu, potentially improve the course of underlying medical conditions such as diabetes or a seizure disorder. This review addresses situations in which menstrual suppression may be of benefit, and lists options which have been successful in inducing medical amenorrhea. PMID:25018654

  15. Oligopeptide cyclophilin inhibitors: a reassessment.

    PubMed

    Schumann, Michael; Jahreis, Günther; Kahlert, Viktoria; Lücke, Christian; Fischer, Gunter

    2011-11-01

    Potent cyclophilin A (CypA) inhibitors such as non-immunosuppressive cyclosporin A (CsA) derivatives have been already used in clinical trials in patients with viral infections. CypA is a peptidyl prolyl cis/trans isomerase (PPIase) that catalyzes slow prolyl bond cis/trans interconversions of the backbone of substrate peptides and proteins. In this study we investigate whether the notoriously low affinity inhibitory interaction of linear proline-containing peptides with the active site of CypA can be increased through a combination of a high cis/trans ratio and a negatively charged C-terminus as has been recently reported for Trp-Gly-Pro. Surprisingly, isothermal titration calorimetry did not reveal formation of an inhibitory CypA/Trp-Gly-Pro complex previously described within a complex stability range similar to CsA, a nanomolar CypA inhibitor. Moreover, despite of cis content of 41% at pH 7.5 Trp-Gly-Pro cannot inhibit CypA-catalyzed standard substrate isomerization up to high micromolar concentrations. However, in the context of the CsA framework a net charge of -7 clustered at the amino acid side chain of position 1 resulted in slightly improved CypA inhibition. PMID:21963115

  16. Next generation fire suppressants

    SciTech Connect

    Brown, J.A.

    1995-03-01

    Spectrex, Inc., located in Cedar Grove, NJ is a manufacturer of fire detection and suppression equipment. Spectrex is one of the original pioneers in high speed fire detection and suppression systems for combat vehicles. Spectrex has installed fire suppressions systems in thousands of combat vehicles and ships throughout the world. Additionally, they manufacture flame explosion detectors, ship damage control systems, and optical gas and vapor detectors. The culmination of several years of research and development has recently produced an innovative electro-optical continuous monitoring systems called SharpEye 20/20I IR(sup 3) and SAFEYE that provide fast and reliable gas, vapor, aerosol, flame, and explosion detection. SharpEye 20/20I IR(sup 3) is a self-contained triple spectrum flame detector which scans for oscillating IR radiation (1 to 10 Hz) in the spectral bands ranging from 4.0 to 5.0 microns and uses programmed algorithms to check the ratio and correlation of data received by the three sensors to make the system highly immune to false alarms. It is extremely sensitive as it can detect a 1 x 1 square foot gasoline pan fire at 200 feet in less than 3 seconds. The sensitivity is user programmable, offering 4 ranges of detection. SAFEYE is comprised of a selected number of multispectral band microprocessor controlled detectors which are in communication with one or more radiation sources that is projected along a 600 feet optical path. The signals from the selected narrow bands are processed and analyzed by highly sophisticated algorithms. It is ideal for high risk, remote, large areas such as petroleum and chemical manufacturing sites, waste dumps, aircraft cargo bays, and ship compartments. The SAFEYE will perform direct readings of the presence or rate of rise of concentrations of gases, vapors, or aerosols at the range of parts per million and provide alarms at various set points at different levels of concentrations.

  17. Next generation fire suppressants

    NASA Technical Reports Server (NTRS)

    Brown, Jerry A.

    1995-01-01

    Spectrex, Inc., located in Cedar Grove, NJ is a manufacturer of fire detection and suppression equipment. Spectrex is one of the original pioneers in high speed fire detection and suppression systems for combat vehicles. Spectrex has installed fire suppressions systems in thousands of combat vehicles and ships throughout the world. Additionally, they manufacture flame explosion detectors, ship damage control systems, and optical gas and vapor detectors. The culmination of several years of research and development has recently produced an innovative electro-optical continuous monitoring systems called SharpEye 20/20I IR(sup 3) and SAFEYE that provide fast and reliable gas, vapor, aerosol, flame, and explosion detection. SharpEye 20/20I IR(sup 3) is a self-contained triple spectrum flame detector which scans for oscillating IR radiation (1 to 10 Hz) in the spectral bands ranging from 4.0 to 5.0 microns and uses programmed algorithms to check the ratio and correlation of data received by the three sensors to make the system highly immune to false alarms. It is extremely sensitive as it can detect a 1 x 1 square foot gasoline pan fire at 200 feet in less than 3 seconds. The sensitivity is user programmable, offering 4 ranges of detection. SAFEYE is comprised of a selected number of multispectral ban microprocessors controlled detectors which are in communication with one or more radiation sources that is projected along a 600 feet optical path. The signals from the selected narrow bands are processed and analyzed by highly sophisticated algorithms. It is ideal for high risk, remote, large areas such as petroleum and chemical manufacturing sites, waste dumps, aircraft cargo bays, and ship compartments. The SAFEYE will perform direct readings of the presence or rate of rise of concentrations of gases, vapors, or aerosols at the range of parts per million and provide alarms at various set points at different levels of concentrations.

  18. Suppression of flutter

    NASA Technical Reports Server (NTRS)

    Nissim, E. (Inventor)

    1973-01-01

    An active aerodynamic control system to control flutter over a large range of oscillatory frequencies is described. The system is not affected by mass, stiffness, elastic axis, or center of gravity location of the system, mode of vibration, or Mach number. The system consists of one or more pairs of leading edge and trailing edge hinged or deformable control surfaces, each pair operated in concert by a stability augmentation system. Torsion and bending motions are sensed and converted by the stability augmentation system into leading and trailing edge control surface deflections which produce lift forces and pitching moments to suppress flutter.

  19. Planck-suppressed operators

    SciTech Connect

    Assassi, Valentin; Baumann, Daniel; Green, Daniel; McAllister, Liam E-mail: dbaumann@damtp.cam.ac.uk E-mail: mcallister@cornell.edu

    2014-01-01

    We show that the recent Planck limits on primordial non-Gaussianity impose strong constraints on light hidden sector fields coupled to the inflaton via operators suppressed by a high mass scale Λ. We study a simple effective field theory in which a hidden sector field is coupled to a shift-symmetric inflaton via arbitrary operators up to dimension five. Self-interactions in the hidden sector lead to non-Gaussianity in the curvature perturbations. To be consistent with the Planck limit on local non-Gaussianity, the coupling to any hidden sector with light fields and natural cubic couplings must be suppressed by a very high scale Λ > 10{sup 5}H. Even if the hidden sector has Gaussian correlations, nonlinearities in the mixing with the inflaton still lead to non-Gaussian curvature perturbations. In this case, the non-Gaussianity is of the equilateral or orthogonal type, and the Planck data requires Λ > 10{sup 2}H.

  20. Giant suppression of flux-flow resistivity in heavy-ion irradiated Tl2Ba2Ca2Cu3O10 films - Influence of linear defects on vortex transport

    NASA Technical Reports Server (NTRS)

    Budhani, R. C.; Suenaga, M.; Liou, S. H.

    1992-01-01

    A large shift of the onset of flux-flow resistivity and the irreversibility line H(irr)(T) to higher temperatures is observed in Tl2Ba2Ca2Cu3O10 films containing linear defects created by Ag(+21) ion irradiation. The H(irr)(T), which has a characteristic L shape in highly anisotropic Tl and Bi based cuprates, becomes more like that of YBa2Cu3O7 in the presence of these defects. The Jc at 77 K also shows a large increase as a result of flux localization at the defects. The transport data indicate that in the H-T plane above H(irr)(T) of the unirradiated material, an ensemble of unoccupied defects is required for effective pinning of each flux line in the system.

  1. Photoperiodic Suppression of Drug Reinstatement

    PubMed Central

    Sorg, Barbara A.; Stark, Gemaine; Sergeeva, Anna; Jansen, Heiko T.

    2011-01-01

    The rewarding influence of drugs of abuse varies with time of day and appears to involve interactions between the circadian and the mesocorticolimbic dopamine systems. The circadian system is also intimately involved in measuring daylength. Thus, the present study examined the impact of changing daylength (photoperiod) on cocaine-seeking behaviors. Male Sprague Dawley rats were trained and tested on a 12L:12D light:dark schedule for cocaine-induced reinstatement of conditioned place preference (CPP) at three times of day (Zeitgeber time (ZT): 4, 12, and 20) to determine a preference score. Rats were then shifted to either shorter (6L:18D) or longer (18L:6D) photoperiods and then to constant conditions, re-tested for cocaine-induced reinstatement under each different condition, and then returned to their original photoperiod (12L:12D) and tested once more. Rats exhibited a circadian profile of preference score in constant darkness with a peak at 12h after lights-off. At both ZT4 and ZT20, but not at ZT12, shorter photoperiods profoundly suppressed cocaine reinstatement, which did not recover even after switching back to 12L:12D. In contrast, longer photoperiods did not alter reinstatement. Separate studies showed that the suppression of cocaine reinstatement was not due to repeated testing. In an additional experiment, we examined the photoperiodic regulation of tyrosine hydroxylase (TH) and dopamine transporter (DAT) proteins in drug-naive rats. These results revealed photoperiodic modulation of proteins in the prefrontal cortex and dorsal striatum, but not in the nucleus accumbens or ventral tegmental area. Together, these findings add further support to the circadian genesis of cocaine-seeking behaviors and demonstrate that drug-induced reinstatement is modulated by photoperiod. Furthermore, the results suggest that photoperiod partly contributes to the seasonal expression of certain drug-related behaviors in humans living at different latitudes and thus our

  2. Factors influencing dust suppressant effectiveness

    SciTech Connect

    Copeland, C.R.; Eisele, T.C.; Chesney, D.J.; Kawatra, S.K.

    2008-11-15

    Water sprays are a common method used to reduce particulate matter (PM) emissions. Various factors such as wettability, surface area coverage, fine particle engulfment rates, interparticle adhesion forces, suppressant penetration and suppressant longevity have all been suggested as critical factors in achieving effective PM control. However, it has not been established which of these factors are the most important. Experimental work indicated that suppressant penetration is the most critical of these factors. The length of time after application that suppressants were effective was also improved by using hygroscopic reagents that retained moisture to prevent evaporation. Maximizing suppressant penetration and improving suppressant longevity led to an average 86% reduction in PM10 concentrations in laboratory dust tower tests.

  3. ZERO SUPPRESSION FOR RECORDERS

    DOEpatents

    Fort, W.G.S.

    1958-12-30

    A zero-suppression circuit for self-balancing recorder instruments is presented. The essential elements of the circuit include a converter-amplifier having two inputs, one for a reference voltage and the other for the signal voltage under analysis, and a servomotor with two control windings, one coupled to the a-c output of the converter-amplifier and the other receiving a reference input. Each input circuit to the converter-amplifier has a variable potentiometer and the sliders of the potentiometer are ganged together for movement by the servoinotor. The particular noveity of the circuit resides in the selection of resistance values for the potentiometer and a resistor in series with the potentiometer of the signal circuit to ensure the full value of signal voltage variation is impressed on a recorder mechanism driven by servomotor.

  4. Interference suppression of SRS

    SciTech Connect

    Kochanov, V P

    2011-01-24

    The theory of three-wave SRS is developed, which takes into account nonlinear dispersion of a medium for arbitrary phases of the pump waves at the input to the medium. The effect of interference suppression of SRS is predicted for values of the total phase of the three-wave pump (2n+1){pi} (n=0, {+-}1, {+-}2...), the effect being caused by the destructive interference of polarisations of the nonresonant dipole-allowed transitions. The relation between the contributions of the linear and nonlinear dispersions to the SRS is found. It is shown that at a sufficiently large wave detuning, the anti-Stokes wave amplitude experiences spatial oscillations. (nonlinear-optics phenomena)

  5. Pressure suppression system

    DOEpatents

    Gluntz, Douglas M.

    1994-01-01

    A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein.

  6. Pressure suppression system

    DOEpatents

    Gluntz, D.M.

    1994-10-04

    A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein. 3 figs.

  7. Optical frequency tripling with improved suppression and sideband selection.

    PubMed

    Thakur, Manoj P; Medeiros, Maria C R; Laurêncio, Paula; Mitchell, John E

    2011-12-12

    A novel optical dispersion tolerant millimetre-wave radio-over-fibre system using optical frequency tripling technique with enhanced and selectable sideband suppression is demonstrated. The implementation utilises cascaded optical modulators to achieve either an optical single sideband (OSSB) or double sideband-suppressed carrier (DSB-SC) signal with high sideband suppression. Our analysis and simulation results indicate that the achievable suppression ratio of this configuration is only limited by other system factors such as optical noise and drifting of the operational conditions. The OSSB transmission system performance is assessed experimentally by the transport of 4 WiMax channels modulating a 10 GHz optical upconverted RF carrier as well as for optical frequency doubling and tripling. The 10 GHz and tripled carrier at 30 GHz are dispersion tolerant resulting both in an average relative constellation error (RCE) of -28.7 dB after 40 km of fibre. PMID:22274056

  8. DEVELOPMENT OF COMPUTER PROGRAM FOR FIRE SUPPRESSANT FLUID FLOW.

    EPA Science Inventory

    The objective of the project is to develop a computer code capable of predicting single and two phase hydrodynamic behavior of fire suppressant fluids during transport through piping systems. This new code will be able to predict pressure losses and flow rates for a wide variety ...

  9. Suppression and restoration of primordial germ cell marker gene expression in channel catfish, Ictalurus punctatus, using knockdown constructs regulated by copper transport protein gene promoters: Potential for reversible transgenic sterilization.

    PubMed

    Su, Baofeng; Shang, Mei; Grewe, Peter M; Patil, Jawahar G; Peatman, Eric; Perera, Dayan A; Cheng, Qi; Li, Chao; Weng, Chia-Chen; Li, Ping; Liu, Zhanjiang; Dunham, Rex A

    2015-12-01

    Complementary DNA overexpression and short hairpin RNA interference approaches were evaluated for decreasing expression of primordial germ cell (PGC) marker genes and thereby sterilizing channel catfish, Ictalurus punctatus, by delivering knockdown constructs driven by a constitutive promoter from yeast and a copper transport protein gene into fish embryos by electroporation. Two PGC marker genes, nanos and dead end, were the target knockdown genes, and their expressions, along with that of an off-target gene, vasa, were evaluated temporally using real-time polymerase chain reaction. Copper sulfate was evaluated as a repressor compound. Some of the constructs knocked down PGC marker gene expression, and some of the constructs were partially repressed by application of 0.1-ppm copper sulfate. When the rate of sexual maturity was compared for three-year-old broodfish that had been exposed to the sterilizing constructs during embryologic development and controls that had not been exposed, several treatments had reduced sexual maturity for the exposed fish. Of two promoter systems evaluated, the one which had been designed to be less sensitive to copper generally was more effective at achieving sterilization and more responsive to repression. Knockdown constructs based on 3' nanos short hairpin RNA interference appeared to result in the best repression and restoration of normal sexual maturity. We conclude that these copper-based systems exhibited good potential for repressible transgenic sterilization. Optimization of this system could allow environmentally safe application of transgenic technology and might be applicable to other applications for aquatic organisms. PMID:26341409

  10. Pathways of Transport Protein Evolution: Recent Advances

    PubMed Central

    Lam, Vincent H.; Lee, Jong-Hoon; Silverio, Abe; Chan, Henry; Gomolplitinant, Kenny M.; Povolotsky, Tatyana L.; Orlova, Ekaterina; Sun, Eric I.; Welliver, Carl H.; Saier, Milton H.

    2014-01-01

    We herein report recent advances in our understanding of transport protein evolution. The Drug-Metabolite Transporter (DMT) superfamily (TC# 2.A.7) arose from a 2TMS precursor to give 4TMS proteins which then added one and duplicated to give 10. The proposed pathway is 2 –> 4 –> 5 –> 10. This superfamily provides a rare example where all proposed topological intermediates in this evolutionary pathway have been identified in current protein databases. Another family, the Oligopeptide Transporter (OPT) family (TC# 2.A.67), also started with a 2 TMS peptide precursor, but it followed the pathway: Only 16 and 17 TMS OPT family members have been identified in current databases. The TRIC family of K+ channels, characterized in animals, arose via the pathway: where the seventh TMS was added c-terminally to the 6 TMS precursor that resulted from a 3 TMS duplication. Surprisingly, animal TRIC channels proved to have numerous 7 TMS homologues in prokaryotes, none of which had been identified previously. We found that two families of integral membrane proteins gave rise to multiple current topological types. Members of the SdpC killer factor immunity protein family, SdpI (TC# 9.A.32) probably arose via the pathway: while members of the Heme Handling Protein (HHP) Family (TC# 9.B.14) arose via the pathway: Predictions are also made for an evolutionary pathway giving rise to the seven topological types of P-type ATPases so far identified in the P-ATPase superfamily. Finally, the ubiquitous CDF carriers (TC# 1.A.4) of 6TMSs probably gave rise to CRAC channels of 4TMSs by loss of the first two TMSs an unusual example of retroevolution. PMID:21194372

  11. STRV Cryocooler Tip Motion Suppression

    NASA Technical Reports Server (NTRS)

    Glaser, R.; Ross, R. G., Jr.; Johnson, D. L.

    1994-01-01

    The Space Technology Research Vehicle (STRV-1b) scheduled to fly at the beginning of June 1994, has a cryocooler vibration suppression experiment aboard doing motion suppression of the tip of the coldfinger. STRV-1b is a bread box sized satellite to be launched on the next flight of the Ariane-4.

  12. An Alternative to Thought Suppression?

    ERIC Educational Resources Information Center

    Boice, Robert

    2012-01-01

    Comments on the original article, "Setting free the bears: Escape from thought suppression," by D. M. Wegner (see record 2011-25622-008). While Wegner supposed that we might have to learn to live with bad thoughts, the present author discusses the use of imagination and guided imagery as an alternative to forced thought suppression.

  13. Nonanesthetics can suppress learning.

    PubMed

    Kandel, L; Chortkoff, B S; Sonner, J; Laster, M J; Eger, E I

    1996-02-01

    Nonanesthetic gases or vapors do not abolish movement in response to noxious stimuli despite partial pressures and affinities for lipids that would, according to the Meyer-Overton hypothesis, predict such abolition. We investigated whether nonanesthetics depress learning and memory (i.e., provide amnesia). To define learning, we used a "fear-potentiated startle paradigm": rats trained to associate light with a noxious stimulus (footshock) will startle more, as measured by an accelerometer, when a startle-eliciting stimulus (e.g., a noise) is paired with light than when the startle-eliciting stimulus is presented alone. We imposed light-shock pairings on 98 rats under three conditions: no anesthesia (control); 0.20, 0.29, and 0.38 times the minimum alveolar anesthetic concentration (MAC) of desflurane; or two nonanesthetics (1,2-dichloroperfluorocyclobutane and perfluoropentane) at partial pressures predicted from their lipid solubilities to be between 0.2 and 1 MAC. Desflurane produced a dose-related depression of learning with abolition of learning at 0.28 MAC. Perfluoropentane at 0.2-predicted MAC had the same effect as 0.28 MAC desflurane. 1,2-Dichloroperfluorocyclobutane at 0.5- to 1-predicted MAC abolished learning. Because nonanesthetics suppress learning but not movement (the two critical components of anesthesia), they may prove useful in discriminating between mechanisms and sites of action of anesthetics. PMID:8561335

  14. Inducing amnesia through systemic suppression.

    PubMed

    Hulbert, Justin C; Henson, Richard N; Anderson, Michael C

    2016-01-01

    Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma. PMID:26977589

  15. Inducing amnesia through systemic suppression

    PubMed Central

    Hulbert, Justin C.; Henson, Richard N.; Anderson, Michael C.

    2016-01-01

    Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma. PMID:26977589

  16. Sound can suppress visual perception.

    PubMed

    Hidaka, Souta; Ide, Masakazu

    2015-01-01

    In a single modality, the percept of an input (e.g., voices of neighbors) is often suppressed by another (e.g., the sound of a car horn nearby) due to close interactions of neural responses to these inputs. Recent studies have also suggested that close interactions of neural responses could occur even across sensory modalities, especially for audio-visual interactions. However, direct behavioral evidence regarding the audio-visual perceptual suppression effect has not been reported in a study with humans. Here, we investigated whether sound could have a suppressive effect on visual perception. We found that white noise bursts presented through headphones degraded visual orientation discrimination performance. This auditory suppression effect on visual perception frequently occurred when these inputs were presented in a spatially and temporally consistent manner. These results indicate that the perceptual suppression effect could occur across auditory and visual modalities based on close and direct neural interactions among those sensory inputs. PMID:26023877

  17. Effect of Proline-Containing Oligopeptides PGP and RGP on Proliferative and Protein-Synthesizing Activity of Cultured Pulmonary Fibroblasts under Conditions of Oxidative Stress.

    PubMed

    Tolstenok, I V; Fleishman, M Yu; Sazonova, E N; Lebed'ko, O A; Maltseva, I M; Myasoedov, N F; Timoshin, S S

    2016-05-01

    We studied the effect of glyprolines Pro-Gly-Pro (PGP) and Arg-Gly-Pro (RGP) on the primary culture of pulmonary fibroblasts from newborn albino rats under normal conditions and during oxidative stress. Under physiological conditions, the peptides had no effect on parameters of cell division. Hydrogen peroxide induced intensive oxidative stress accompanied by suppression of protein-synthesizing function. When hydrogen peroxide was added to the culture containing the test peptides, correction of the oxidative status was observed accompanied by activation of DNA-synthesizing activity and inhibition of lucigenin-dependent chemiluminescence. PMID:27265140

  18. Coating Thermoelectric Devices To Suppress Sublimation

    NASA Technical Reports Server (NTRS)

    Sakamoto, Jeffrey; Caillat, Thierry; Fleurial, Jean-Pierre; Snyder, G. Jeffrey

    2007-01-01

    . This was a considerable improvement, considering that uncoated CoSb3 had been found to decompose to form the lowest antimonide at the surface at only 600 C. Evidently, because the mean free path of Sb at the given temperature and pressure was of the order of tens of centimeters, any barrier closer than tens of centimeters (as was the niobium foil) would have suppressed transport of Sb vapor, thereby suppressing sublimation of Sb

  19. Enantioselective Synthesis of (2R, 3S)- and (2S, 3R)-4,4,4-trifluoro-N-Fmoc-O-tert-butyl-threonine and their Racemization-free Incorporation into Oligopeptides via Solid-phase Synthesis

    PubMed Central

    Xiao, Nu; Jiang, Zhong-Xing; Yu, Y. Bruce

    2010-01-01

    An efficient method for the enantioselective synthesis of (2R, 3S)- and (2S, 3R)-4,4,4-trifluoro-N-Fmoc-O-tert-butyl-threonine (tfT) on multi-gram scales was developed. Absolute configurations of the two stereoisomers were ascertained by X-ray crystallography. Racemization-free coupling conditions for the incorporation of tfT into oligopeptides were then explored. For solution-phase synthesis, tfT racemization was not an issue under conventional coupling conditions. For solid-phase synthesis, the following conditions were identified to achieve racemization-free synthesis: if tfT (3.0 eq.) was not the first amino acid to be linked to the resin (1.0 eq.), the condition is: 2.7 eq. DIC/3.0 eq. HOBt as the coupling reagent at 0 °C for 20 h; if tfT (3.0 eq.) was the first amino acid to be linked to the resin (1.0 eq.), then 1.0 eq. of CuCl2 needs to be added to the coupling reagent. PMID:17702025

  20. Suppressive drug interactions between antifungals.

    PubMed

    de Vos, Marjon G J; Bollenbach, Tobias

    2014-04-24

    In this issue of Chemistry & Biology, Cokol and colleagues report a systematic study of drug interactions between antifungal compounds. Suppressive drug interactions occur more frequently than previously realized and come in different flavors with interesting implications. PMID:24766845

  1. Substrate specificity and mapping of residues critical for transport in the high-affinity glutathione transporter Hgt1p.

    PubMed

    Zulkifli, Mohammad; Yadav, Shambhu; Thakur, Anil; Singla, Shiffalli; Sharma, Monika; Bachhawat, Anand Kumar

    2016-08-01

    The high-affinity glutathione transporter Hgt1p of Saccharomyces cerevisiae belongs to a relatively new and structurally uncharacterized oligopeptide transporter (OPT) family. To understand the structural features required for interaction with Hgt1p, a quantitative investigation of substrate specificity of Hgt1p was carried out. Hgt1p showed a higher affinity for reduced glutathione (GSH), whereas it transported oxidized glutathione (GSSG) and other glutathione conjugates with lower affinity. To identify the residues of Hgt1p critical for substrate binding and translocation, all amino acid residues of the 13 predicted transmembrane domains (TMDs) have been subjected to mutagenesis. Functional evaluation of these 269 mutants by growth and biochemical assay followed by kinetic analysis of the severely defective mutants including previous mutagenic studies on this transporter have led to the identification of N124 (TMD1), V185 (TMD3), Q222, G225 and Y226 (TMD4), P292 (TMD5), Y374 (TMD6), L429 (TMD7) and F523 and Q526 (TMD9) as critical for substrate binding with at least 3-fold increase in Km upon mutagenesis to alanine. In addition residues Y226 and Y374 appeared to be important for differential substrate specificity. An ab initio model of Hgt1p was built and refined using these mutagenic data that yielded a helical arrangement that includes TMD3, TMD4, TMD5, TMD6, TMD7, TMD9 and TMD13 as pore-lining helices with the functionally important residues in a channel-facing orientation. Taken together the results of this study provides the first mechanistic insights into glutathione transport by a eukaryotic high-affinity glutathione transporter. PMID:27252386

  2. Suppressed Charmed B Decay

    SciTech Connect

    Snoek, Hella Leonie

    2009-06-02

    This thesis describes the measurement of the branching fractions of the suppressed charmed B0 → D*- a0+ decays and the non-resonant B0 → D*- ηπ+ decays in approximately 230 million Υ(4S) → B$\\bar{B}$ events. The data have been collected with the BABAR detector at the PEP-II B factory at the Stanford Linear Accelerator Center in California. Theoretical predictions of the branching fraction of the B0 → D*- a{sub 0}+ decays show large QCD model dependent uncertainties. Non-factorizing terms, in the naive factorization model, that can be calculated by QCD factorizing models have a large impact on the branching fraction of these decay modes. The predictions of the branching fractions are of the order of 10-6. The measurement of the branching fraction gives more insight into the theoretical models. In general a better understanding of QCD models will be necessary to conduct weak interaction physics at the next level. The presence of CP violation in electroweak interactions allows the differentiation between matter and antimatter in the laws of physics. In the Standard Model, CP violation is incorporated in the CKM matrix that describes the weak interaction between quarks. Relations amongst the CKM matrix elements are used to present the two relevant parameters as the apex of a triangle (Unitarity Triangle) in a complex plane. The over-constraining of the CKM triangle by experimental measurements is an important test of the Standard Model. At this moment no stringent direct measurements of the CKM angle γ, one of the interior angles of the Unitarity Triangle, are available. The measurement of the angle γ can be performed using the decays of neutral B mesons. The B0 → D*- a0+ decay is sensitive to the angle γ and, in comparison to the current decays that are being employed, could significantly

  3. Line defect induced conductance suppression in graphene nanojunction

    NASA Astrophysics Data System (ADS)

    Li, Haidong; Li, Ruixue; Yu, Qiongyan; Kang, Xiubao; Ding, Jun

    2016-05-01

    Line defect induced conductance suppression in graphene nanojunction is investigated by means of Landauer-Bütikker formula and the nonequilibrium Green's function technique. With the increase of the longitudinal size of the device region, the conductance value decreases and tends to form two conductance valleys. Then we prove that the line defect can lead to localize states in the device region, which contributes to conductance valley at the point far away from Dirac point. And the zero conductance at the Dirac point is associated with the edge state localized at the zigzag-edged shoulder of the nanojunctions. The staggered potential can change energy spectrum structure of the device region, and produce strong conductance suppression. The line defect can efficiently enhance the conductance suppression, which can be utilized to realize the electron transport manipulation.

  4. Resolving the mystery of transport within internal transport barriers

    SciTech Connect

    Staebler, G. M.; Belli, E. A.; Candy, J.; Waltz, R. E.; Greenfield, C. M.; Lao, L. L.; Smith, S. P.; Kinsey, J. E.; Grierson, B. A.; Chrystal, C.

    2014-05-15

    The Trapped Gyro-Landau Fluid (TGLF) quasi-linear model [G. M. Staebler, et al., Phys. Plasmas 12, 102508 (2005)], which is calibrated to nonlinear gyrokinetic turbulence simulations, is now able to predict the electron density, electron and ion temperatures, and ion toroidal rotation simultaneously for internal transport barrier (ITB) discharges. This is a strong validation of gyrokinetic theory of ITBs, requiring multiple instabilities responsible for transport in different channels at different scales. The mystery of transport inside the ITB is that momentum and particle transport is far above the predicted neoclassical levels in apparent contradiction with the expectation from the theory of suppression of turbulence by E×B velocity shear. The success of TGLF in predicting ITB transport is due to the inclusion of ion gyro-radius scale modes that become dominant at high E×B velocity shear and to improvements to TGLF that allow momentum transport from gyrokinetic turbulence to be faithfully modeled.

  5. The amphetamine appetite suppressant saga.

    PubMed

    2004-02-01

    (1) In 1999, all amphetamine derivatives still sold in France as appetite suppressants were withdrawn from the market because of serious cardiovascular adverse effects. Sibutramine, marketed in France since 2001, is closely related to this group of drugs. (2) The adverse effects shared by these drugs are mainly neuropsychiatric (due to a psychostimulant action) and cardiovascular (arterial hypertension and tachycardia). (3) More specific cardiovascular adverse effects, such as pulmonary hypertension and severe cardiac valve damage, emerged after several years of use. The first reports date back to the 1960s. (4) The pulmonary hypertension associated with appetite suppressants can be fatal or necessitate transplantation. (5) Cardiac valve damage due to appetite suppressants is generally irreversible and sometimes requires surgery. PMID:15055225

  6. Visual Surround Suppression in Schizophrenia

    PubMed Central

    Tibber, Marc S.; Anderson, Elaine J.; Bobin, Tracy; Antonova, Elena; Seabright, Alice; Wright, Bernice; Carlin, Patricia; Shergill, Sukhwinder S.; Dakin, Steven C.

    2013-01-01

    Compared to unaffected observers patients with schizophrenia (SZ) show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgments of contrast – a manifestation of weaker surround suppression (SS). To examine the generality of this phenomenon we measured the ability of 24 individuals with SZ to judge the luminance, contrast, orientation, and size of targets embedded in contextual surrounds that would typically influence the target’s appearance. Individuals with SZ demonstrated weaker SS compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation SS in SZ may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies. PMID:23450069

  7. Vibration suppression using smart structures

    NASA Technical Reports Server (NTRS)

    Garcia, Ephrahim; Inman, Daniel J.; Dosch, Jeffrey

    1991-01-01

    The control of structures for vibration suppression is discussed in the context of using smart materials and structures. Here the use of smart structures refers to using embedded piezoelectric devices as both control actuators and sensors. Using embedded sensors and actuators allows great improvements in performance over traditional structures (both passive and active) for vibration suppression. The application of smart structures to three experimental flexible structures is presented. The first is a flexible beam, the second is a flexible beam undergoing slewing motion, the third is a ribbed antenna. A simple model of a piezoelectric actuator/sensor is presented. The equations of motion for each structure is presented. The control issues considered as those associated with multi-input, multi-output control, PID control and LQR control implementation. A modern control analysis illustrates the usefulness of smart structures for vibration suppression.

  8. Background suppression in MAS NMR

    NASA Astrophysics Data System (ADS)

    White, Jeffery L.; Beck, Larry W.; Ferguson, David B.; Haw, James F.

    Pulse sequences for suppressing background signals from spinning modules used in magic-angle spinning NMR are described. These pulse sequences are based on spatially selective composite 90° pulses originally reported by Bax, which provide for no net excitation of spins outside the homogeneous region of the coil. We have achieved essentially complete suppression of background signals originating from our Vespel spinning module (which uses a free-standing coil) in both 1H and 13C spectra without notable loss in signal intensity. Successful modification of both Bloch decay and cross-polarization pulse sequences to include spatially selective pulses was essential to acquire background-free spectra for weak samples. Background suppression was also found to be particularly valuable for both T1 and T1 ϱ, relaxation measurements.

  9. Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds.

    PubMed

    Yoshida, Ryusuke; Noguchi, Kenshi; Shigemura, Noriatsu; Jyotaki, Masafumi; Takahashi, Ichiro; Margolskee, Robert F; Ninomiya, Yuzo

    2015-11-01

    Leptin is known to selectively suppress neural and behavioral responses to sweet-tasting compounds. However, the molecular basis for the effect of leptin on sweet taste is not known. Here, we report that leptin suppresses sweet taste via leptin receptors (Ob-Rb) and KATP channels expressed selectively in sweet-sensitive taste cells. Ob-Rb was more often expressed in taste cells that expressed T1R3 (a sweet receptor component) than in those that expressed glutamate-aspartate transporter (a marker for Type I taste cells) or GAD67 (a marker for Type III taste cells). Systemically administered leptin suppressed taste cell responses to sweet but not to bitter or sour compounds. This effect was blocked by a leptin antagonist and was absent in leptin receptor-deficient db/db mice and mice with diet-induced obesity. Blocking the KATP channel subunit sulfonylurea receptor 1, which was frequently coexpressed with Ob-Rb in T1R3-expressing taste cells, eliminated the effect of leptin on sweet taste. In contrast, activating the KATP channel with diazoxide mimicked the sweet-suppressing effect of leptin. These results indicate that leptin acts via Ob-Rb and KATP channels that are present in T1R3-expressing taste cells to selectively suppress their responses to sweet compounds. PMID:26116698

  10. Aging and repeated thought suppression success.

    PubMed

    Lambert, Ann E; Smyth, Frederick L; Beadel, Jessica R; Teachman, Bethany A

    2013-01-01

    Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility. PMID:23776442

  11. Noise suppressing capillary separation system

    DOEpatents

    Yeung, Edward S.; Xue, Yongjun

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans.

  12. RAGE Suppresses ABCG1-Mediated Macrophage Cholesterol Efflux in Diabetes.

    PubMed

    Daffu, Gurdip; Shen, Xiaoping; Senatus, Laura; Thiagarajan, Devi; Abedini, Andisheh; Hurtado Del Pozo, Carmen; Rosario, Rosa; Song, Fei; Friedman, Richard A; Ramasamy, Ravichandran; Schmidt, Ann Marie

    2015-12-01

    Diabetes exacerbates cardiovascular disease, at least in part through suppression of macrophage cholesterol efflux and levels of the cholesterol transporters ATP binding cassette transporter A1 (ABCA1) and ABCG1. The receptor for advanced glycation end products (RAGE) is highly expressed in human and murine diabetic atherosclerotic plaques, particularly in macrophages. We tested the hypothesis that RAGE suppresses macrophage cholesterol efflux and probed the mechanisms by which RAGE downregulates ABCA1 and ABCG1. Macrophage cholesterol efflux to apolipoprotein A1 and HDL and reverse cholesterol transport to plasma, liver, and feces were reduced in diabetic macrophages through RAGE. In vitro, RAGE ligands suppressed ABCG1 and ABCA1 promoter luciferase activity and transcription of ABCG1 and ABCA1 through peroxisome proliferator-activated receptor-γ (PPARG)-responsive promoter elements but not through liver X receptor elements. Plasma levels of HDL were reduced in diabetic mice in a RAGE-dependent manner. Laser capture microdissected CD68(+) macrophages from atherosclerotic plaques of Ldlr(-/-) mice devoid of Ager (RAGE) displayed higher levels of Abca1, Abcg1, and Pparg mRNA transcripts versus Ager-expressing Ldlr(-/-) mice independently of glycemia or plasma levels of total cholesterol and triglycerides. Antagonism of RAGE may fill an important therapeutic gap in the treatment of diabetic macrovascular complications. PMID:26253613

  13. Suppressing explosive synchronization by contrarians

    NASA Astrophysics Data System (ADS)

    Zhang, Xiyun; Guan, Shuguang; Zou, Yong; Chen, Xiaosong; Liu, Zonghua

    2016-01-01

    Explosive synchronization (ES) has recently received increasing attention and studies have mainly focused on the conditions of its onset so far. However, its inverse problem, i.e. the suppression of ES, has not been systematically studied so far. As ES is usually considered to be harmful in certain circumstances such as the cascading failure of power grids and epileptic seizure, etc., its suppression is definitely important and deserves to be studied. We here study this inverse problem by presenting an efficient approach to suppress ES from a first-order to second-order transition, without changing the intrinsic network structure. We find that ES can be suppressed by only changing a small fraction of oscillators into contrarians with negative couplings and the critical fraction for the transition from the first order to the second order increases with both the network size and the average degree. A brief theory is presented to explain the underlying mechanism. This finding underlines the importance of our method to improve the understanding of neural interactions underlying cognitive processes.

  14. Stimulus Fractionation by Interocular Suppression

    PubMed Central

    Zadbood, Asieh; Lee, Sang-Hun; Blake, Randolph

    2011-01-01

    Can human observers distinguish physical removal of a visible stimulus from phenomenal suppression of that stimulus during binocular rivalry? As so often happens, simple questions produce complex answers, and that is the case in the study reported here. Using continuous flash suppression to produce binocular rivalry, we were able to identify stimulus conditions where most – but not all – people utterly fail to distinguish physical from phenomenal stimulus removal, although we can be certain that those two equivalent perceptual states are accompanied by distinct neural events. More interestingly, we find subtle variants of the task where distinguishing the two states is trivially easy, even for people who utterly fail under the original conditions. We found that stimulus features are differentially vulnerable to suppression. Observers are able to be aware of existence/removal of some stimulus attributes (flicker) but not others (orientation), implying that interocular suppression breaks down the unitary awareness of integrated features belonging to a visual object. These findings raise questions about the unitary nature of awareness and, also, place qualifications on the utility of binocular rivalry as a tool for studying the neural concomitants of conscious visual awareness. PMID:22102839

  15. Charmonium suppression in nuclear collisions

    SciTech Connect

    Gavin, S. |

    1996-11-01

    Measurements of {psi} and {psi}{prime} production from experiment NA50 at the CERN SPS are compared to calculations based on a hadronic model of charmonium suppression developed previously. Data on centrality dependence and total cross sections are in good accord with these predictions. Uncertainties in theoretical quantities such as NA50`s L parameter are discussed.

  16. Conditioned suppression, punishment, and aversion

    NASA Technical Reports Server (NTRS)

    Orme-Johnson, D. W.; Yarczower, M.

    1974-01-01

    The aversive action of visual stimuli was studied in two groups of pigeons which received response-contingent or noncontingent electric shocks in cages with translucent response keys. Presentation of grain for 3 sec, contingent on key pecking, was the visual stimulus associated with conditioned punishment or suppression. The responses of the pigeons in three different experiments are compared.

  17. DENDRITIC POLYMERS AS FIRE SUPPRESSANTS

    EPA Science Inventory

    This report describes an evaluation of the applicability of one of the latest advances in polymer technology (dendritic polymers) to suppressing fires, one of the greatest survivability threats to military personnel and vehicles. Certain types of alkali and transition metal compl...

  18. Multiple cilia suppress tumour formation.

    PubMed

    Eberhart, Charles

    2016-04-01

    Primary cilia are cellular structures that have important functions in development and disease. The suppression of multiciliate differentiation of choroid plexus precursors, and maintenance of a single primary cilium by Notch1, is now shown to be involved in choroid plexus tumour formation. PMID:27027488

  19. Radiation Transport

    SciTech Connect

    Urbatsch, Todd James

    2015-06-15

    We present an overview of radiation transport, covering terminology, blackbody raditation, opacities, Boltzmann transport theory, approximations to the transport equation. Next we introduce several transport methods. We present a section on Caseology, observing transport boundary layers. We briefly broach topics of software development, including verification and validation, and we close with a section on high energy-density experiments that highlight and support radiation transport.

  20. High temperature suppression of dioxins.

    PubMed

    Zhan, Ming-Xiu; Chen, Tong; Fu, Jian-Ying; Lin, Xiao-Qing; Lu, Sheng-Yong; Li, Xiao-Dong; Yan, Jian-Hua; Buekens, Alfons

    2016-03-01

    Combined Sulphur-Nitrogen inhibitors, such as sewage sludge decomposition gases (SDG), thiourea and amidosulphonic acid have been observed to suppress the de novo synthesis of dioxins effectively. In this study, the inhibition of PCDD/Fs formation from model fly ash was investigated at unusually high temperatures (650 °C and 850 °C), well above the usual range of de novo tests (250-400 °C). At 650 °C it was found that SDG evolving from dried sewage sludge could suppress the formation of 2,3,7,8-substituted PCDD/Fs with high efficiency (90%), both in weight units and in I-TEQ units. Additionally, at 850 °C, three kinds of sulphur-amine or sulphur-ammonium compounds were tested to inhibit dioxins formation during laboratory-scale tests, simulating municipal solid waste incineration. The suppression efficiencies of PCDD/Fs formed through homogeneous gas phase reactions were all above 85% when 3 wt. % of thiourea (98.7%), aminosulphonic acid (96.0%) or ammonium thiosulphate (87.3%) was added. Differences in the ratio of PCDFs/PCDDs, in weight average chlorination level and in the congener distribution of the 17 toxic PCDD/Fs indicated that the three inhibitors tested followed distinct suppression pathways, possibly in relation to their different functional groups of nitrogen. Furthermore, thiourea reduced the (weight) average chlorinated level. In addition, the thermal decomposition of TUA was studied by means of thermogravimetry-fourier transform infrared spectroscopy (TG-FTIR) and the presence of SO2, SO3, NH3 and nitriles (N≡C bonds) was shown in the decomposition gases; these gaseous inhibitors might be the primary dioxins suppressants. PMID:26716881

  1. Transportation Planning with Immune System Derived Approach

    NASA Astrophysics Data System (ADS)

    Sugiyama, Kenji; Yaji, Yasuhito; Ootsuki, John Takuya; Fujimoto, Yasutaka; Sekiguchi, Takashi

    This paper presents an immune system derived approach for planning transportation of materials between manufacturing processes in the factory. Transportation operations are modeled by Petri Net, and divided into submodels. Transportation orders are derived from the firing sequences of those submodels through convergence calculation by the immune system derived excitation and suppression operations. Basic evaluation of this approach is conducted by simulation-based investigation.

  2. Suppression of the Richtmyer-Meshkov Instability in the Presence of a Magnetic Field

    SciTech Connect

    Ravi Samtaney

    2003-03-21

    We present numerical evidence from two dimensional simulations that the growth of the Richtmyer-Meshkov instability is suppressed in the presence of a magnetic field. A bifurcation occurs during the refraction of the incident shock on the density interface which transports baroclinically generated vorticity away from the interface to a pair of slow or intermediate magnetosonic shocks. Consequently, the density interface is devoid of vorticity and its growth and associated mixing is completely suppressed.

  3. Fire alarm system/fire suppression system for mobile tactical shelters

    NASA Astrophysics Data System (ADS)

    Walker, F. K.; Lecours, C. A.; Radcliff, O.

    1985-08-01

    The objective of this project was to develop a fire detection/suppression capability for DoD standard family mobile tactical shelters. The systems developed and tested provide complete protection during all employment conditions; in garrison use, storage, transportation, and deployed field conditions. The reports outlines the requirement and the test and evaluation program. Two manufacturers of detection systems and two manufacturers of suppression systems were identified and qualified to meet the fire protection requirements for mobile tactical shelters.

  4. Pupil Transportation.

    ERIC Educational Resources Information Center

    Stollar, Dewey H.

    The purpose of this NEFP satellite study is to provide an overview of pupil transportation. The first phase of the study discusses the early legal and financial bases for student transportation, the second the current status of student transportation, and the third the future status of student transportation needs and financing for 1980.…

  5. Noise suppressing capillary separation system

    DOEpatents

    Yeung, E.S.; Xue, Y.

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans. 13 figs.

  6. M-COPA, a novel Golgi system disruptor, suppresses apoptosis induced by Shiga toxin.

    PubMed

    Hattori, Takayuki; Watanabe-Takahashi, Miho; Shiina, Isamu; Ohashi, Yoshimi; Dan, Shingo; Nishikawa, Kiyotaka; Yamori, Takao; Naito, Mikihiko

    2016-08-01

    Shiga toxin (Stx) is a main virulence factor of Stx-producing Escherichia coli (STEC) that contributes to diarrhea and hemorrhagic colitis and occasionally to fatal systemic complications. Therefore, the development of an antidote to neutralize Stx toxicity is urgently needed. After internalization into cells, Stx is transferred to the Golgi apparatus via a retrograde vesicular transport system. We report here that 2-methylcoprophilinamide (M-COPA), a compound that induces disassembly of the Golgi apparatus by inactivating ADP-ribosylation factor 1 (Arf1), suppresses Stx-induced apoptosis. M-COPA inhibited transport of Stx from the plasma membrane to the Golgi apparatus and suppressed degradation of anti-apoptotic proteins and the activation of caspases. These findings suggest that inhibition of Stx retrograde transport by M-COPA could be a novel approach to suppress Stx toxicity. PMID:27302278

  7. Isoform-selective Inhibition of Facilitative Glucose Transporters

    PubMed Central

    Hresko, Richard C.; Kraft, Thomas E.; Tzekov, Anatoly; Wildman, Scott A.; Hruz, Paul W.

    2014-01-01

    Pharmacologic HIV protease inhibitors (PIs) and structurally related oligopeptides are known to reversibly bind and inactivate the insulin-responsive facilitative glucose transporter 4 (GLUT4). Several PIs exhibit isoform selectivity with little effect on GLUT1. The ability to target individual GLUT isoforms in an acute and reversible manner provides novel means both to investigate the contribution of individual GLUTs to health and disease and to develop targeted treatment of glucose-dependent diseases. To determine the molecular basis of transport inhibition, a series of chimeric proteins containing transmembrane and cytosolic domains from GLUT1 and GLUT4 and/or point mutations were generated and expressed in HEK293 cells. Structural integrity was confirmed via measurement of N-[2-[2-[2-[(N-biotinylcaproylamino)ethoxy)ethoxyl]-4-[2-(trifluoromethyl)-3H-diazirin-3-yl]benzoyl]-1,3-bis(mannopyranosyl-4-yloxy)-2-propylamine (ATB-BMPA) labeling of the chimeric proteins in low density microsome fractions isolated from stably transfected 293 cells. Functional integrity was assessed via measurement of zero-trans 2-deoxyglucose (2-DOG) uptake. ATB-BMPA labeling studies and 2-DOG uptake revealed that transmembrane helices 1 and 5 contain amino acid residues that influence inhibitor access to the transporter binding domain. Substitution of Thr-30 and His-160 in GLUT1 to the corresponding positions in GLUT4 is sufficient to completely transform GLUT1 into GLUT4 with respect to indinavir inhibition of 2-DOG uptake and ATB-BMPA binding. These data provide a structural basis for the selectivity of PIs toward GLUT4 over GLUT1 that can be used in ongoing novel drug design. PMID:24706759

  8. A dendrite-suppressing composite ion conductor from aramid nanofibres.

    PubMed

    Tung, Siu-On; Ho, Szushen; Yang, Ming; Zhang, Ruilin; Kotov, Nicholas A

    2015-01-01

    Dendrite growth threatens the safety of batteries by piercing the ion-transporting separators between the cathode and anode. Finding a dendrite-suppressing material that combines high modulus and high ionic conductance has long been considered a major technological and materials science challenge. Here we demonstrate that these properties can be attained in a composite made from Kevlar-derived aramid nanofibres assembled in a layer-by-layer manner with poly(ethylene oxide). Importantly, the porosity of the membranes is smaller than the growth area of the dendrites so that aramid nanofibres eliminate 'weak links' where the dendrites pierce the membranes. The aramid nanofibre network suppresses poly(ethylene oxide) crystallization detrimental for ion transport, giving a composite that exhibits high modulus, ionic conductivity, flexibility, ion flux rates and thermal stability. Successful suppression of hard copper dendrites by the composite ion conductor at extreme discharge conditions is demonstrated, thereby providing a new approach for the materials engineering of solid ion conductors. PMID:25626170

  9. Altered srf expression in Bacillus subtilis resulting from changes in culture pH is dependent on the Spo0K oligopeptide permease and the ComQX system of extracellular control.

    PubMed

    Cosby, W M; Vollenbroich, D; Lee, O H; Zuber, P

    1998-03-01

    The expression of the srf operon of Bacillus subtilis, encoding surfactin synthetase and the competence regulatory protein ComS, was observed to be reduced when cells were grown in a rich glucose- and glutamine-containing medium in which late-growth culture pH was 5.0 or lower. The production of the surfactin synthetase subunits and of surfactin itself was also reduced. Raising the pH to near neutrality resulted in dramatic increases in srf expression and surfactin production. This apparent pH-dependent induction of srf expression required spo0K, which encodes the oligopeptide permease that functions in cell-density-dependent control of sporulation and competence, but not CSF, the competence-inducing pheromone that regulates srf expression in a Spo0K-dependent manner. Both ComP and ComA, the two-component regulatory pair that stimulates cell-density-dependent srf transcription, were required for optimal expression of srf at low and high pHs, but ComP was not required for pH-dependent srf induction. The known negative regulators of srf, RapC and CodY, were found not to function significantly in pH-dependent srf expression. Late-growth culture supernatants at low pH were not active in inducing srf expression in cells of low-density cultures but were rendered active when their pH was raised to near neutrality. ComQ (and very likely the srf-inducing pheromone ComX) and Spo0K were found to be required for the extracellular induction of srf-lacZ at neutral pH. The results suggest that srf expression, in response to changes in culture pH, requires Spo0K and another, as yet unidentified, extracellular factor. The study also provides evidence consistent with the hypothesis that ComP acts both positively and negatively in the regulation of ComA and that both activities are controlled by the ComX pheromone. PMID:9515911

  10. Suppression of edge-localized modes by magnetic field perturbations

    SciTech Connect

    Kleva, Robert G.; Guzdar, Parvez N.

    2010-11-15

    Transport bursts in simulations of edge-localized modes (ELMs) in tokamaks are suppressed by the application of magnetic field perturbations. The amplitude of the applied magnetic field perturbations is characterized by a stochasticity parameter S. When S>1, magnetic flux surfaces are destroyed and the magnetic field lines diffuse in minor radius. As S increases in the simulations, the magnitude of the ELM bursts decreases. The size of bursts is reduced to a very small value while S is still less than unity and most of the magnetic flux surfaces are still preserved. Magnetic field line stochasticity is not a requirement for the stabilization of ELMs by the magnetic field perturbations. The magnetic field perturbations act by suppressing the growth of the resistive ballooning instability that underlies the ELM bursts.